| Toxicological ie] - 1, 2-DICHLOROETHENE (Update) U.S. DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease RTI (a; WBLIC HEALTH LIBRARY 7 BERKELEY LIBRARY gives TY OF CALIF. HHA TOXICOLOGICAL PROFILE FOR 1,2-DICHLOROETHENE Prepared by: Research Triangle Institute Under Contract No. 205-93-0606 Prepared for: U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry August 1996 1,2-DICHLOROETHENE DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. CAT. FOR PUBLIC HEALTH EA dz iii 1,2-DICHLOROETHENE |2 E 7 T 6% 1 9 6 p UEL A Toxicological Profile for 1,2-dichloroethene was released in December 1990. This edition supersedes any previously released draft or final profile. UPDATE STATEMENT Toxicological profiles are revised and republished as necessary, but no less than once every three years. For information regarding the update status of previously released profiles, contact ATSDR at: Agency for Toxic Substances and Disease Registry Division of Toxicology/Toxicology Information Branch 1600 Clifton Road NE, E-29 Atlanta, Georgia 30333 FOREWORD This toxicological profile is prepared in accordance with guidelines* developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary. The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for the hazardous substance described therein. Each peer-reviewed profile identifies and reviews the key literature that describes a hazardous substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile begins with a public health statement that describes, in nontechnical language, a substance's relevant toxicological properties. Following the public health statement is information concerning levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine a substance's health effects is described in a health effects summary. Data needs that are of significance to protection of public health are identified by ATSDR and EPA. Each profile includes the following: (A) The examination, summary, and interpretation of available toxicologic information and epidemiologic evaluations on a hazardous substance to ascertain the levels of significant human exposure for the substance and the associated acute, subacute, and chronic health effects: (B) A determination of whether adequate information on the health effects of each substance is available or in the process of development to determine levels of exposure that present a significant risk to human health of acute, subacute, and chronic health effects; and (C) Where appropriate, identification of toxicologic testing needed to identify the types or levels of exposure that may present significant risk of adverse health effects in humans. The principal audience for the toxicological profiles is health professionals at the Federal, State, and local levels; interested private sector organizations and groups; and members of the public. This profile reflects ATSDR’s assessment of all relevant toxicologic testing and information that has been peer-reviewed. Staff of the Centers for Disease Control and Prevention and other Federal scientists have also reviewed the profile. In addition, this profile has been peer-reviewed by a nongovernmental panel and was made available for public review. Final responsibility for the contents and views expressed in this toxicological profile resides with ATSDR. DTS ohh David Satcher, M.D., Ph.D. Administrator Agency for Toxic Substances and Disease Registry vi *Legislative Background The toxicological profiles are developed in response to the Superfund Amendments and Reauthorization Act (SARA) of 1986 (Public Law 99-499) which amended the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund). This public law directed ATSDR to prepare toxicological profiles for hazardous substances most commonly found at facilities on the CERCLA National Priorities List and that pose the most significant potential threat to human health, as determined by ATSDR and the EPA. The availability of the revised priority list of 275 hazardous substances was announced in the Federal Register on April 29, 1996 (61 FR 18744). For prior versions of the list of substances, see Federal Register notices dated April 17, 1987 (52 FR 12866); October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR 43619); October 17,1990 (55 FR 42067); October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 48801); and February 28, 1994 (59 FR 9486). Section 104(T)(3) of CERCLA, as amended, directs the Administrator of ATSDR to prepare a toxicological profile for each substance on the list. 1,2-DICHLOROETHENE vii CONTRIBUTORS CHEMICAL MANAGER(S)/AUTHORS(S): Carolyn Harper, Ph.D. ATSDR, Division of Toxicology, Atlanta, GA Robert Chessin, M.S.P.H. Research Triangle Institute, Research Triangle Park, NC Susan Goldhaber, M.P.H. Research Triangle Institute, Research Triangle Park, NC THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 1. Green Border Review. Green Border review assures consistency with ATSDR policy. 2. Health Effects Review. The Health Effects Review Committee examines the health effects chapter of each profile for consistency and accuracy in interpreting health effects and classifying end points. 3. Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to substance-specific minimal risk levels (MRLs), reviews the health effects database of each profile, and makes recommendations for derivation of MRLs. 1,2-DICHLOROETHENE ix PEER REVIEW A peer review panel was assembled for 1,2-dichloroethene. The panel consisted of the following members: 1. Dr. Frederick Guengerich, Vanderbilt University School of Medicine, Department of Biochemistry, Nashville, Tennessee; 2. Dr. Derek Hodgson, Provost and Vice President of Academic Affairs, Mississippi State University, Mississippi State, Mississippi; 3. Dr. Norman Trieff, Professor of Environmental Toxicology, University of Texas Medical Branch, Galveston, Texas; and 4. Dr. Benjamin Van Duuren, Private Consultant, New York, New York. These experts collectively have knowledge of 1,2-dichloroethene's physical and chemical properties, toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer review specified in Section 104(i)(13) of the Comprehensive Environmental Response, Compensation, and Liability Act, as amended. Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the peer reviewers' comments and determined which comments will be included in the profile. A listing of the peer reviewers' comments not incorporated in the profile, with a brief explanation of the rationale for their exclusion, exists as part of the administrative record for this compound. A list of databases reviewed and a list of unpublished documents cited are also included in the administrative record. The citation of the peer review panel should not be understood to imply its approval of the profile's final content. The responsibility for the content of this profile lies with the ATSDR. 1,2-DICHLOROETHENE xi CONTENTS FOREWORD ott ee ee v CONTRIBUTORS vc rvs mas mamas mms ms mms mms bom ds hE SHES BR ABA» HERES EME HES #® 3 vii PEERREVIEW .... ¢cinconian:mtint dhs $s amen t U0 Eat Ea rapes Baa me muy oo vo ix LIST OF FIGURES . . ©. ot ee ee eee XV LISTOP TABLES .....vvenmumsnmemaims nd isd sai ®B Bet Ha BR GRE 0 2 HME me 0p» xvii 1. PUBLIC HEALTH STATEMENT . .. eee ees 1 1.1 WHATIS 1,2-DICHLOROETHENE? ....... 2 1.2 WHAT HAPPENS TO 1,2-DICHLOROETHENE WHEN IT ENTERS THEENVIRONMENTZ .. ons ni onsninias tsa sams ss pas game nwt may was 2 1.3 HOW MIGHT I BE EXPOSED TO 1,2-DICHLOROETHENE? ................... 3 1.4 HOW CAN 1,2-DICHLOROETHENE ENTER AND LEAVE MY BODY? ........... 3 1.5 HOW CAN 1,2-DICHLOROETHENE AFFECT MY HEALTH? ................... 4 1.6 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED TO 1,2-DICHLOROETHENE? ........... i. 4 1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TOPROTECTHUMAN HEALTH? . . ccc vv ininnssntnnsnmamsvmons sms rms vss 4 1.8 WHERE CAN I GET MORE INFORMATION? ......... i iiiiiin.. 5 2. HEALTH EPFECTS . ions vn sc vasme mss vd 5m sams ns GR pH BES WE HRS WE ARE HTH LS 7 21 INTRODUCTION cc uns un imenmome sims ans kis s SE e 95 t Bs pus £m 5% s a « sw so 0 na 7 2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ............... 7 2.2.1 Inhalation EXpPosSUre . ..:c:oscsasamsvmsnmsnssnsuwsosvmonmsmnrns ve 9 22.1.1 Death . o.oo 9 2212 SystemicBffects .....c cccsurrncnninervssmisnsnssn suns 9 2.2.1.3 Immunological and Lymphoreticular Effects . .................. 17 2.2.1.4 Neurological Effects .................. 18 22.1.5 Reproductive Effects ........ veces vvnruviasvssnsnnsvnns 18 221.86 Developmental Effects . ... co ven cvnivasmevvimnsvsnns anny 19 2.2.1.7 Genotoxic Effects ........... 19 2201.8 CaNCEr .. otitis 19 222 OrdlEBXposure ......c.cocvirncnmrsancnsrafiovsnsvnissonssnsenso 20 2221 Death ...cvvviininmines mason sams menu: Smsns ens ses es 20 2222 SystemC BffectS sv unm snsvursmenrssmernsomsnsswsmavnns ns 29 2.2.2.3 Immunological and Lymphoreticular Effects . .................. 34 2224 Neurological Bffects .........cccoiiniuumivinnsvesnsnuens 35 2223 Reproductive Effects .. vc: vnnvurvmsmnmsnivnsnnsnsnmsns 36 2226 Developmental Effects .. sous vvsnrevvsnrrsnsnrsvssosnns on 36 2.2.2.7 Genotoxic Effects ........... 36 D228 CANCEL «vu vms vn rmrnmrmme mama sas ssa sb Boni bd sob snns un 36 1,2-DICHLOROETHENE xii 3. 4. 5. 223 Demmal Exposure ..........c.cuveeunnrnrverrannnnnsansnnsnmsnss 37 DAD DAI «uv vns mn sas Bonn inst ommmemmemsmw sons mmsnnses 37 2232 SysiemiCEHeotS . ovovr rns rans ns00s6008 nme mmcnmemn nnn 37 2.23.3 Immunological and Lymphoreticular Effects . .................. 40 2.23.4 Neurological Effects ................................... 40 2.23.5 Reproductive Effects ................................... 40 223.6 Developmental Effects .................................. 40 2237 OCenotoxic Effects .verv:sorns sss snsisinismevonnrmmamesn 40 2238 CaANCET .... ii 40 2.3 TOXICOKINETICS . . 40 23.0 ADPBOTPHON «.uicvirasocivmrmenmsnmsmosmomasmenmnmsnssnsanssss 40 231.0 Inhalation BXposure . .:..:s: 0s :nustismrmrnmrrencnnsnmennn 40 23.1.2 Oral Exposure .......................... 41 23.1.3 Dermal Exposure . ............. LL... 41 237 DIiStrIDUHON « : sits a i mm inmmrnssmrmmrsmsn sms smenmennmennssnsnns 41 233 Metabolism ....... LL 41] 234 Excretion ...................... EE El Rl 44 24 MECHANISMS OF ACTION ..... 44 2.5 RELEVANCE TO PUBLIC HEALTH ...................... iii... 45 2.6 BIOMARKERS OF EXPOSURE AND EFFECT .................0uiiiuiiii.. 52 2.6.1 Biomarkers Used to Identify or Quantify Exposure to 1,2-Dichloroethene . . . . . . 57 2.6.2 Biomarkers Used to Characterize Effects Caused by 1,2-Dichloroethene . . . . . . . 57 2.7 INTERACTIONS WITH OTHER CHEMICALS ............................. 58 2.8 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE . ................... 58 2.9 METHODS FOR REDUCING TOXIC EFFECTS ............................ 59 29.1 Reducing Peak Absorption Following Exposure . ....................... 59 292 Reducing Body Burden . ..................... ..... 60 29.3 Interfering with the Mechanism of Action for Toxic Effects ............... 60 2.10 ADEQUACY OF THE DATABASE... .... i, 61 2.10.1 Existing Information on Health Effects of 1,2-Dichloroethene .............. 61 2.10.2 Identification of Data Needs ..................................... 64 2.10.3 Ongoing Studies ............. 72 CHEMICAL AND PHYSICAL INFORMATION . ................. iii... 73 3.1 CHEMICAL IDENTITY . ........ 73 3.2 PHYSICAL AND CHEMICAL PROPERTIES .............................. 73 PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL ........................ 77 4.1 PRODUCTION . ds 77 42 IMPORT/EXPORT : civ iin onisnsnssmennrmnmsnnmarsmosmcnsmesnssmsmns an 77 43 USE 79 4.4 DISPOSAL . . 79 POTENTIAL FOR HUMAN EXPOSURE . . ............... i. 81 5.1 OVERVIEW 81 5.2 RELEASES TO THE ENVIRONMENT ..................... iin... 82 BL AI chit ninti inn nm vas wa me mw EEE EE EE NE AEA 82 BUD WEIBE «vst 65 4 955 86 55 5 Gms mon von sms won wwe mo mn ws ww mesma 87 Be | ER 89 1,2-DICHLOROETHENE Xiii 53.1 Transportand Partitioning . .« co seve vu vn vnsnon ans omovies rata ta un 90 5.3.2 Transformationand Degradation . . . ............c.ciutiiueeneennnnnnn 91 5.3.2.1 AIT «ee eee 91 5.327 Wa. co vo cn vn tr tin ik nd RA BA MA NR RA WIRE RI RAMEE EE RE hee 93 5.3.2.3 Sedimentand Soil . ........ ee eee 95 5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT .............. 96 BAL AIL yin nn rir rs in mn mn me x wh dh Ek RE AA RA PARE RI RIB EE EE RE RE wa 96 5.4.2 Wallr «vo i ttt tt te eee ee ee eee eee 99 5.43 Sedimentand Soil ........... i ee 107 5.4.4 Other Environmental Media . . . ........... 00 t ttt. 108 5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE ................ 109 5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES .................. 110 5.7 ADEQUACY OFTHE DATABASE . . ..... iit titi e ieee eee 110 5.7.1 Identificationof Data Needs . . . . . . oo ci iii i iii ite tt iit eee 110 5.72 Ongoing SdIes .....vcvevi sini ss ts nT urs sR IR PRLS IE PE AE RE HE 114 6. ANALYTICAL METHODS . . ttt ttt ttt tet ee eee ee eee eee 115 6.1 BIOLOGICAL SAMPLES ... itt titi e test ieee ieee 115 6.2 ENVIRONMENTAL SAMPLES . . . .. itt ttt ee eee ee een 117 6.3 ADEQUACY OF THE DATABASE . . . ... titi itt ite tite eens 121 6.3.1 Identificationof Data Needs . . . . . ..... ci iii iii iii tte eeennnn 122 6.37 OngoinzSdies ....cvcvivnuininimonosnivsnsnmsnnn assess ss uss 123 7. REGULATIONS AND ADVISORIES . . iit tt tet ee ee eee en 125 8. REFERENCES . . ttt ttt ee ee ee ee eee ee ee eee e een 135 OD. GLOSSARY ...vvuvsriniss Bini ai NiRimiRiRiMiRIMNeUI FI RAE BO UE OF BF NE GF» 157 APPENDICES A. MINIMAL RISK LEVEL (MRL) WORKSHEET(S) . .......... cui iiiennen.. A-3 B. USER'S GUIDE . ... ttt tt te ee eet ee ee eee een B-1 C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS .......................... C-1 1,2-DICHLOROETHENE XV 2-1 2-2 2-3 2-5 5-1 5-3 LIST OF FIGURES Levels of Significant Exposure to 1,2-Dichloroethene - Inhalation .................... 13 Levels of Significant Exposure to 1,2-Dichloroethene - Oral . ....................... 27 Proposed Metabolic Scheme for 1,2-Dichloroethene . . ............................ 43 Existing Information on Health Effects of cis-1,2-Dichloroethene .................... 62 Existing Information on Health Effects of trans-1,2-Dichloroethene . .................. 63 Frequency of Sites with cis-1,2-Dichloroethene Contamination ...................... 83 Frequency of Sites with trans-1,2-Dichloroethene Contamination . . ................... 84 Frequency of Sites with 1,2-Dichloroethene (Unspecified) Contamination . . ............. 85 1,2-DICHLOROETHENE XVii 2-1 2-2 2-4 2-5 3-1 4-1 5-1 5-2 5-3 6-1 7-1 LIST OF TABLES Levels of Significant Exposure to 1,2-Dichloroethene - Inhalation .................... 10 Levels of Significant Exposure to 1,2-Dichloroethene - Oral . ....................... 21 Levels of Significant Exposure to 1,2-Dichloroethene - Dermal . ..................... 38 Genotoxicity of cis- and trans-1,2-Dichloroethene In Vivo ......................... 53 Genotoxicity of cis- and trans-1,2-Dichloroethene In Vitro ......................... 54 Chemical Identity of 1,2-Dichloroethene . ..................................... 74 Physical and Chemical Properties of cis- and trans-1,2-Dichloroethene . . ............... 75 Facilities That Manufacture or Process 1,2-Dichloroethene ......................... 78 Releases to the Environment from Facilities That Manufacture or Process 1,2-Dichloroethene . .................. 86 Air Monitoring Data for 1,2-Dichloroethene .................. ................. 97 Water Monitoring Data for 1,2-Dichloroethene ................................ 100 Analytical Methods for Determining 1,2-Dichloroethene in Biological Samples . . ........ 116 Analytical Methods for Determining 1,2-Dichloroethene in Environmental Samples . . . . .. 118 Regulations and Guidelines Applicable to trans- and cis-1,2-Dichloroethene . ........... 127 1,2-DICHLOROETHENE 1 1. PUBLIC HEALTH STATEMENT This public health statement tells you about 1,2-dichloroethene and the effects of exposure. The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for long-term federal cleanup activities. Cis-1,2-dichloroethene has been found in at least 146 of the 1,430 current or former NPL sites. Trans-1,2-dichloroethene has been found in at least 563 of the 1,430 current or former NPL sites. In 336 of the NPL sites, 1,2-dichloroethene was found but the isomer was not specified. However, it’s unknown how many NPL sites have been evaluated for this substance. As more sites are evaluated, the sites with 1,2-dichloroethene may increase. This information is important because exposure to this substance may harm you and because these sites may be sources of exposure. When a substance is released from a large area, such as an industrial plant, or from a container, such as a drum or bottle, it enters the environment. This release does not always lead to exposure. You are exposed to a substance only when you come in contact with it. You may be exposed by breathing, eating, or drinking the substance or by skin contact. If you are exposed to 1,2-dichloroethene, many factors determine whether you’ll be harmed. These factors include the dose (how much), the duration (how long), and how you come in contact with it. You must also consider the other chemicals you're exposed to and your age, sex, diet, family traits, lifestyle, and state of health. 1.1 WHAT IS 1,2-DICHLOROETHENE? 1,2-Dichloroethene is also called 1,2-dichloroethylene. It is a highly flammable, colorless liquid with a sharp, harsh odor. You can smell very small amounts of 1,2-dichloroethene in air (beginning at a level of about 17 parts per million or ppm). There are two forms of 1,2-dichloroethene; one form is called cis-1,2-dichloroethene and the other is called 1,2-DICHLOROETHENE 2 1. PUBLIC HEALTH STATEMENT 1.1 WHAT IS 1,2-DICHLOROETHENE? 1,2-Dichloroethene is also called 1,2-dichloroethylene. It is a highly flammable, colorless liquid with a sharp, harsh odor. You can smell very small amounts of 1,2-dichloroethene in air (beginning at a level of about 17 parts per million or ppm). There are two forms of 1,2-dichloroethene; one form is called cis-1,2-dichloroethene and the other is called trans-1,2-dichloroethene. Sometimes both forms are present as a mixture. 1,2-Dichloroethene is used most often to produce solvents and in chemical mixtures. 1,2-Dichloroethene enters the environment through industrial activity of people. This chemical has been found in air, water, and soil. 1,2-Dichloroethene is released to the environment from chemical factories that make or use this chemical, from landfills and hazardous waste sites containing this chemical, from chemical spills, from burning of objects made of vinyl, and from breakdown of other chlorinated chemicals. 1.2 WHAT HAPPENS TO 1,2-DICHLOROETHENE WHEN IT ENTERS THE ENVIRONMENT? 1,2-Dichloroethene evaporates rapidly. When released to moist soil surfaces or to lakes, rivers, and other bodies of water, most of it evaporates into the air. Once in the air, it usually takes about 5-12 days for half of any amount of it to break down (half-life in air). 1,2-Dichloroethene that is below soil surfaces in landfills or hazardous waste sites may dissolve in water, seep deeper into the soil, and possibly contaminate groundwater. Some 1,2-dichloroethene may escape as a vapor. Once in groundwater, it takes about 13-48 weeks for half of a given amount to break down (half-life in water). There is a slight chance that small amounts of the 1,2-dichloroethene found in landfills will eventually break down into vinyl chloride, which is believed to be a more hazardous chemical. 1,2-DICHLOROETHENE 1. PUBLIC HEALTH STATEMENT 1.3 HOW MIGHT | BE EXPOSED TO 1,2-DICHLOROETHENE? You might be exposed to 1,2-dichloroethene by breathing contaminated air or by drinking contaminated tap water. If the tap water in your home is contaminated, you could also be breathing 1,2-dichloroethene vapors while cooking, bathing, or washing dishes. There are no known products you can buy that contain 1,2-dichloroethene. People who are most likely to be exposed live near landfills and hazardous waste sites that contain this chemical, work at factories where this chemical is made or used, work at 1,2-dichloroethene contaminated landfills, or work as firefighters. Job-related exposure results from breathing in 1,2-dichloro- ethene from workplace air or from touching contaminated chemicals or materials. According to a survey conducted between 1981 and 1983 by the National Institute for Occupational Safety and Health (NIOSH), an estimated 215 people in the United States may have been exposed to 1,2-dichloroethene while working. People who live in cities or suburbs are more likely to be exposed than people living in rural areas. Most people who are exposed to 1,2-dichloroethene through air or water are exposed to very low levels, in the range of parts per million (ppm) to parts per billion (ppb). 1.4 HOW CAN 1,2-DICHLOROETHENE ENTER AND LEAVE MY BODY? 1,2-Dichloroethene can enter the body through your lungs when you breathe air contaminated with it, through your stomach and intestines when you eat food or drink water contaminated with it, or through your skin upon contact with the chemical. When 1,2-dichloroethene enters the body, the blood and other tissues absorb it. It is broken down to other compounds in the liver. Animal studies have looked at how quickly the compound enters and leaves the body and what may happen to it in the body. These animal studies describe effects at levels far greater than those levels at which most people would be exposed. No studies show specifically how 1,2-dichloroethene enters a person's body and how it is changed or removed by the body. 1,2-DICHLOROETHENE 4 1. PUBLIC HEALTH STATEMENT 1.5 HOW CAN 1,2-DICHLOROETHENE AFFECT MY HEALTH? Breathing high levels of trans-1,2-dichloroethene can make you feel nauseous, drowsy, and tired. Breathing very high levels of its vapor can kill you. When animals breathed high levels of trans-1,2-dichloroethene for short or longer periods of time, their livers and lungs were damaged. The effects were more severe with longer exposure times. Animals that breathed very high levels of trans-1,2-dichloroethene had damaged hearts. Animals given extremely high doses of cis- or trans-1,2-dichloroethene by mouth died. Lower oral doses of cis-1,2-dichloroethene caused effects on the blood, such as decreased numbers of red blood cells, and effects on the liver. The long-term human health effects after exposure to low concentrations of 1,2-dichloroethene are not known. Results of a recent animal study suggest that an exposed fetus may not grow as quickly as one that is not exposed. No studies have been done to see whether cancer in people or animals is caused by exposure to 1,2-dichloroethene; exposure has not been shown to affect fertility in people or animals. 1.6 IS THERE A MEDICAL TEST TO DETERMINE WHETHER | HAVE BEEN EXPOSED TO 1,2-DICHLOROETHENE? Methods are available to measure concentrations of 1,2-dichloroethene in blood, urine, and tissues. However, these methods are not routinely used to determine whether a person has been exposed to this compound, because the expected breakdown products resulting from exposure to 1,2-dichloroethene may also result from exposure to other chemicals. 1.7 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO PROTECT HUMAN HEALTH? The federal government has developed regulatory standards and guidelines to protect people from possible health effects of 1,2-dichloroethene in water and air. The EPA has established 1,2-DICHLOROETHENE 5 1. PUBLIC HEALTH STATEMENT water quality guidelines to protect both aquatic life and people who eat fish and shellfish. The EPA Office of Drinking Water has set a drinking water regulation that states that water delivered to any user of a public water system shall not exceed 0.07 milligrams per liter (mg/L) for cis-1,2-dichloroethene and 0.1 mg/L for trans-1,2-dichloroethene. For very short- term exposures (1 day) for children, EPA advises that concentrations in drinking water should not be more than 4 mg/L for cis-1,2-dichloroethene or 20 mg/L for trans-1,2-dichloroethene. For 10-day exposures for children, EPA advises that drinking water concentrations should not be more than 3 mg/L for cis-1,2-dichloroethene or 2 mg/L for trans-1,2-dichloroethene. For industrial or waste disposal sites, any release of 1,000 pounds or more must be reported to the EPA. The National Institute for Occupational Safety and Health (NIOSH) and the American Conference of Governmental Industrial Hygienists (ACGIH) have established guidelines for occupational exposure to cis- or trans-1,2-dichloroethene. Average concentrations should not exceed 200 ppm in the air. 1.8 WHERE CAN | GET MORE INFORMATION? If you have any more questions or concerns, contact your community or state health or environmental quality department or: Agency for Toxic Substances and Disease Registry Division of Toxicology 1600 Clifton Road NE, E-29 Atlanta, Georgia 30333 Phone: 404-639-6000 This agency can also tell you where to find occupational and environmental health clinics. These clinics specialize in recognizing, evaluating, and treating illness resulting from exposure to hazardous substances. 1,2-DICHLOROETHENE z 2. HEALTH EFFECTS 2.1 INTRODUCTION The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective of the toxicology of 1,2-dichloro- ethene. It contains descriptions and evaluations of toxicological studies and epidemiological investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. There are two geometric isomers of 1,2-dichloroethene, the cis form and the trans form. Isomers of an organic substance are different structures with the same molecular formula. In this case, the cis and trans forms have the chlorine atoms in different positions around the double bond. Each of these geometric isomeric forms has slightly different physical, chemical, and biological properties, because of their different molecular structures. These properties determine how the compound may affect the health of exposed individuals and how 1,2-dichloroethene behaves in air, water, and soil. The trans isomer is the more common industrial product. A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE To help public health professionals and others address the needs of persons living or working near hazardous waste sites, the information in this section is organized first by route of exposure —inhalation, oral, and dermal; and then by health effect—death, systemic, immunological, neurological, reproductive, developmental, genotoxic, and carcinogenic effects. These data are discussed in terms of three exposure periods—acute (14 days or less), intermediate (15-364 days), and chronic (365 days or more). Levels of significant exposure for each route and duration are presented in tables and illustrated in figures. The points in the figures showing no-observed-adverse-effect levels (NOAELSs) or lowest- observed-adverse-effect levels (LOAELS) reflect the actual doses (levels of exposure) used in the studies. LOAELS have been classified into "less serious” or "serious" effects. "Serious" effects are 1,2-DICHLOROETHENE 8 2. HEALTH EFFECTS those that evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute respiratory distress or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death, or those whose significance to the organism is not entirely clear. ATSDR acknowledges that a considerable amount of judgment may be required in establishing whether an end point should be classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be insufficient data to decide whether the effect is indicative of significant dysfunction. However, the Agency has established guidelines and policies that are used to classify these end points. ATSDR believes that there is sufficient merit in this approach to warrant an attempt at distinguishing between "less serious” and "serious" effects. The distinction between "less serious” effects and "serious" effects is considered to be important because it helps the users of the profiles to identify levels of exposure at which major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not the effects vary with dose and/or duration, and place into perspective the possible significance of these effects to human health. The significance of the exposure levels shown in the LSE tables and figures may differ depending on the user's perspective. Public health officials and others concerned with appropriate actions to take at hazardous waste sites may want information on levels of exposure associated with more subtle effects in humans or animals (LOAEL) or exposure levels below which no adverse effects (NOAELSs) have been observed. Estimates of levels posing minimal risk to humans (Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike. Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for 1,2-dichloroethene. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990a), uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges 1,2-DICHLOROETHENE 9 2. HEALTH EFFECTS additional uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an example, acute inhalation MRLs may not be protective for health effects that are delayed in development or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic bronchitis. As these kinds of health effects data become available and methods to assess levels of significant human exposure improve, these MRLs will be revised. A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 2.2.1 Inhalation Exposure 2.2.1.1 Death A single fatality was reported to have occurred after inhalation of 1,2-dichloroethene vapor in a small enclosure (Hamilton 1934). Neither the level and duration of exposure associated with the fatality nor the symptoms of toxicity were reported. The isomeric composition of the vapor was not reported. No further information regarding lethal effects in humans following inhalation of 1,2-dichloroethene could be located in the literature. The lethality of a single exposure by inhalation of trans-1,2-dichloroethene has been determined in mice (Gradiski et al. 1978). The lethal concentration resulting in 50% fatalities (LCs) was 21,723 ppm trans-1,2-dichloroethene, presented in Table 2-1 and in Figure 2-1, and was for a single 6-hour exposure. The cause of death was not reported. No other studies were located regarding lethality following inhalation exposure to cis- or trans-1,2-dichloroethene in any animal species. 2.2.1.2 Systemic Effects No studies were located regarding gastrointestinal, endocrine, dermal, or ocular effects in humans or animals after inhalation exposure to cis- or trans-1,2-dichloroethene. The highest NOAEL values and all LOAEL values from each reliable study for each systemic effect in each species and duration category are recorded in Table 2-1 and plotted in Figure 2-1. Table 2-1. Levels of Significant Exposure to 1,2-Dichloroethene - Inhalation . Exposure/ LOAEL Keyto Species duration/ NOAEL Less serious Serious figure (strain) frequency System (ppm) (ppm) (ppm) Reference ACUTE EXPOSURE Death 1 Mouse 6 hr 21723 F (LC) Gradiski et al. (OF1,SPF) 1978 trans Systemic 2 Rat 8 hr Resp 200 F (slight hyperemia of lung Freundt et al. (Wistar SPF) with alveolar septum 1977 distention in 6/6) trans Cardio 1000 F 3000 F (severe fibrous swelling and hyperemia, barely maintained striation in 2/6) Hemato 200 F 1000 F (decreased erythrocyte count) Musc/skel 3000 F Hepatic 200b F (slight fatty degeneration) 1000 F (slight to severe fatty degeneration of lobules in 2/6) Renal 3000 F 3 Rat 1-2 wk Resp 200 F (slight capillary Freundt et al. (Wistar SPF) 5 d/wk hyperemia and alveolar 1977 8 hr/d septum distention in all trans rats) Cardio 200 F Musc/skel 200 F Hepatic 200 F (slight fatty accumulation in liver lobule) Renal 200 F S103443 H1IV3IH ¢ 3INIHL30HOTHOIa-2't ot Table 2-1. Levels of Significant Exposure to 1,2-Dichloroethene - Inhalation (continued) a Exposure/ LOAEL Keyto Species duration/ NOAEL Less serious Serious figure (strain) frequency System (ppm) (ppm) (ppm) Reference 4 Rat 10d Bd Wt 2000 F 6000 F (reduced body weight 12000 F (reduced body weight gain Hurt et al. 1993 (CD,BR) Gd 7-16 gain of dams of 13%) of 33%) trans 8 hid Other 2000 F (reduced food consumption of dams on gestational days 13-15) Immunological/Lymphoreticular 5 Rat 8 hr 200 F 1000 F (slight degeneration of Freundt et al. (Wistar SPF) Kuppfer cells in 2/6) 1977 trans 6 Rat 1-2 wk 200 F (slight fatty Freundt et al. (Wistar SPF) 5 d/wk accumulation in Kupffer 1977 8 hr/d cells) trans 7 Rat 8 hr 200 F (decreased leukocyte Freundt et al. (Wistar SPF) count) 1977 trans Neurological 8 Rat 10d 6000 F 12000 F (lethargy and salivation) Hurtt et al. 1993 (CD,BR) Gd 7-16 trans 6 hr/d 9 Mouse 4 hr 1582 M 1720M (45% decreased De Ceaurriz et al. (Swiss OF1) duration of immobility in 1983 behavioral despair NS swimming test) Developmental 10 Rat 10d 6000 12000 (significant decrease in Hurtt et al. 1993 (ch: cpBR) Gd 7-16 mean fetal weight) trans 6 hr/d 3IN3IHL30HOHOIa-2'+ S103443 H1IV3H 2 LE Table 2-1. Levels of Significant Exposure to 1,2-Dichloroethene - Inhalation (continued) . Exposure/ LOAEL Keyto Species duration/ NOAEL Less serious Serious figure (strain) frequency System (ppm) (ppm) Bom) Reference INTERMEDIATE EXPOSURE Systemic 11 Rat 8or16 wk Resp 200 F (slight capillary Freundt et al. (Wistar SPF) 5 d/wk hyperemia and alveolar 1977 8 hr/d system distention) trans Cardio 200 F Musc/skel 200 F Hepatic 200c¢ F (slight fatty accumulation in liver lobules) Renal 200 F Immunological/Lymphoreticular 12 Rat 8 or 16 wk 200 F (slight fatty Freundt et al. (Wistar SPF) 5 d/wk accumulation in Kupffer 1977 8 hr/d cells) trans The number corresponds to entries in Figure 2-1. b Used to derive an acute inhalation minimal risk level (MRL) of 0.2 ppm. Concentration is adjusted by an uncertainty factor of 1,000 (10 for use of a LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability). ‘Used to derive an intermediate inhalation MRL of 0.2 ppm. Concentration is adjusted by an uncertainty factor of 1,000 (10 for use of a LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability). Bd Wt = body weight; Cardio = cardiovascular; d = day(s); F = female; Gd = gestational day; Hemato = hematological; hr = hour(s); LCs, = lethal concentration, 50% kill; LOAEL = lowest-observable-adverse-effect level; M = male; Musc/skel = musculoskeletal; NOAEL = no-observable-adverse-effect level; Resp = respiratory; wk = week(s). S103443 HIV3H ¢ IN3IHLIIOHOTHOIa-2'+ 4} Figure 2-1. Levels of Significant Exposure to 1,2-Dichloroethene - Inhalation INIHL30HOHOIA-2 + S103443 H1IV3aH 2 Acute (<14 days) Systemic & XS SN 5 ~ ¥ 3 $ s EF ~ 2 S $ > $ o $& g & 9 & NS S$ £ SS) » Q s £& §& FF J § > , $8 $$ pom) F&F § § 8 8 5 ¥ & £€ F Q & o £ S IL & Q S £2 < Q 100000 im N 4r 8r >, 10000 | ®, or ® 2r 2r 2r TO Ov Or oO O 4r Sm T T T TO 0 NSO) 2r 2r 2r ar T 5r oO 1000 | 0 0 ® o 9m T T T T NS 2r 3r 3r 2r 3r 2r 3r 3r 5r 6r Ir 00 0 0 oO 0, O o 00 O0 T T T T T J T T T T TR 100 | | 1 1 : Key 1 » L . r rat BW (C, (animals) , Minimal risk m mouse @ LOAEL for serious effects (animals) 1 level for , t effects other 1 OQ LOAEL for less serious effects (animals) vv than cancer O NOAEL (animals) 1 F 1 . The number next to each point corresponds to entries in Table 2-1. 1 C=cis; T=trans; NS = not specified WV 01 + el Figure 2-1. (mg/kg/day) 100000 10000 1000 100 10 0.1 Intermediate (15-364 days) Levels of Significant Exposure to 1,2-Dichloroethene - Inhalation (continued) Systemic > \ O&O ¥ g EF S O 2 S = 9 & eg OQ Q > XN +£ QQ -& QO S Ng ~ § 5 Q 5 S T ® Q & $ S & & §§ & oO > ¥ rd & 9 s > S & & Ny & & &P © g < § s§ & F&F © >» $F FF (mghkgday) F I I SA & ss F&F 10000 S < © 0 _X ~ oS EF FF FI [ 7 4r @c T 5m 6m or '® m 8r 8r 8r 8r 0 8r 8r 8r 11r LR Oc Oc O ne x ° = © © O ® im i 3r TT a 2 C © c O o 8r c Cc Cc 8r ¢ 3 T T T T 100 | ® ¢@ ac Oc O mT T C T T 11r Tr Tr 8r 8r Cc 8r 8r Cc Oc 13m 10m @ 10m ® om 10m 10m 0 0 c Or c 0 0 0 CT T 8r 8r T T 13m 100 | Oc oO Oo . C CT 1 1 1 ’ Key 10 | ! t : r ra nu LDsq (animals) : Minimal risk m mouse ! @ LOAEL for serious effects (animals) 1 level for ! . . 1 effects other Q LOAEL for less serious effects (animals) J than cancer I O NOAEL (animals) 1 - UJ The number next to each point corresponds to entries in Table 2-2. C=cis; T=trans; NS = not specified 0.1 + S103443 H1TV3H 2 3INTHL30HOHOIa-2'L 22 Figure 2-2. Levels of Significant Exposure to 1,2-Dichloroethene - Oral (continued) Intermediate (15-364 days) Systemic N > N @ yoo F S$ $< FS & & & S © SO SF © L & > & & N ¥ 1S £ $ S ® > § S S$ & L Ss (mg/kg/day) KR & » & $ & & S$ & > ¢ LK 2 > > > 2 & & O $ & 8 & J ao F S L & Q Sd SJ 10000 14r 14r 14r 14r Or oO Oo Oo T T i § 14r 15¢ 15¢ 15 15¢ (RT 15r 15r 1000 | Oc OF T oO O CT16r 47m 16r 16r 16r Cc 16r Cc 161 17m C C 16r 47m 16r 19m 3 or Oo Oo ® ad w 00 sw © O O Oo CT 47m CT CT CT CT Oo OCT T @ CT 7 CT 18m T b 17m rr C 0 J T 15r 15r T 15r 100 | ac Oc o C 15r 15r 15r Oc Oc Oo 18m | 17m Cc Oo 1 or T 1 1 10 1 1 1 1 Key 1 I _ ! ! ro rat BW |p, (animals) i Minimal ! ! m mouse : } 1 risk level ; ! @ LOAEL for serious effects (animals) ' for aiferts 1 1 ; : I Q LOAEL for less serious effects (animals) \u/ other than - 1 cancer 1 I O NOAEL (animals) I 1 WU \ The number next to each point corresponds to entries in Table 2-2. 1 C=cis; T=trans; NS = not specified Ww 01 + S103443 H1TV3H ¢ 3INIHLIOHOHOIA-2't 8¢ 1,2-DICHLOROETHENE 29 2. HEALTH EFFECTS 2.2.2.2 Systemic Effects No studies were located regarding ocular effects in humans or animals after oral exposure to cis- or trans-1,2-dichloroethene. The highest NOAEL values and all LOAEL values from each reliable study for each systemic effect in each species and duration category are recorded in Table 2-2 and plotted in Figure 2-2. Respiratory Effects. No studies were located regarding respiratory effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. The effects of orally administered 1,2-dichloroethene on the respiratory tract of animals have not been examined extensively. As shown in Table 2-2 and Figure 2-2, male mice have been shown to tolerate exposure to 387 mg/kg body weight per day of trans-1,2-dichloroethene administered in drinking water for up to 90 days without developing histopathological changes in the lung (Barnes et al. 1985). The only change reported in this study was a slight decrease (11%) in lung weight in female mice at 452 mg/kg/day. No change in lung weight occurred in male rats exposed to 3,114 mg/kg/day trans-1,2-dichloroethene for 90 days (Hayes et al. 1987). Pulmonary capillary hyperemia and alveolar septal distention have been observed in rats given lethal doses of trans-1,2-dichloroethene (Freundt et al. 1977). It is not clear whether this pathology represents a primary effect of the chemical on the lung or is secondary to disruption of cardiovascular function prior to death. It is notable that similar changes have been observed in rats exposed by inhalation to trans-1,2-dichloroethene (see Section 2.2.1.2). Cardiovascular Effects. No studies were located regarding cardiovascular effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. Female rats exposed to 1,130-1,400 mg/kg trans-1,2-dichloroethene through oral gavage (single exposure) showed changes in cardiac muscle structure along with swelling and hyperemia (Freundt et al. 1977). No cardiovascular effects were noted in rats exposed to 1,900 mg/kg/day cis-1,2-dichloro- ethene for 14 days or 870 mg/kg/day cis-1,2-dichloroethene for 90 days (McCauley et al. 1990). Gastrointestinal Effects. No studies were located regarding gastrointestinal effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. 1,2-DICHLOROETHENE 30 2. HEALTH EFFECTS Mice that received lethal doses of trans-1,2-dichloroethene had hyperemia of the stomach and small intestines (Barnes et al. 1985). No gastrointestinal effects were noted in rats exposed to 1,900 mg/kg/day cis-1,2-dichloroethene for 14 days or 870 mg/kg/day cis-1,2-dichloroethene for 90 days (McCauley et al. 1990). Hematological Effects. No studies were located regarding hematological effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. McMillan (1986) reported unchanged values of electrolytes, total blood cell counts, and total leukocyte counts, as compared to controls, from 14-day administration of a 50% mixture of the 1,2-dichloro- ethene cis and trans isomers (480 mg/kg/day) in rats. In contrast, the same dose, administered over 30 days, resulted in a significant depression of the total blood cell count, the red blood cell count, peripheral blood hemoglobin, and hematocrit levels. No significant changes in hematological parameters occurred in rats (Hayes et al. 1987) or mice (Barnes et al. 1985) following oral exposure to trans-1,2-dichloroethene. As shown in Table 2-2 and Figure 2-2, rats tolerated repeated doses of 3,114 mg/kg/day (males) and 2,809 mg/kg/day (females) of trans-1,2-dichloroethene in drinking water (emulsified with emulphor, a polyethoxylated vegetable oil) for 90 days without exhibiting significant hematological abnormalities (Barnes et al. 1985; Hayes et al. 1987). In contrast, dose-related hematotoxicity was the most evident effect in rats exposed orally by gavage to cis-1,2-dichloroethene in corn oil (McCauley et al. 1990). Decreased red blood cell count and hematocrit levels were observed in female rats exposed to 290 mg/kg/day for 14 days. No such changes were detected in female rats after exposure to 97 mg/kg/day or in male rats at all dose levels. Based on this value, an acute-duration oral MRL of 1 mg/kg/day was calculated for cis-1,2-dichloro- ethene as described in the footnote to Table 2-2 and in Appendix A. Similarly, decreased hematocrit levels were found in male rats exposed to 97 mg/kg/day cis-1,2-dichloroethene for 90 days and decreased hemoglobin levels were reported in both sexes at 290 mg/kg/day. The NOAEL level was 32 mg/kg/day. This value was used for derivation of an intermediate-duration oral MRL for cis-1,2-dichloroethene of 0.3 mg/kg/day as described in the footnote to Table 2-2 and in Appendix A. Musculoskeletal Effects. No studies were located regarding musculoskeletal effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. 1,2-DICHLOROETHENE 31 2. HEALTH EFFECTS Histological examination of muscle tissue revealed no compound-related effects in rats exposed to 1,900 or 870 mg/kg/day of cis-1,2-dichloroethene for 14 or 90 days, respectively (McCauley et al. 1990), or in rats exposed by gavage to 1,600 mg/kg/day of trans-1,2-dichloroethene (Freundt et al. 1977). Hepatic Effects. No studies were located regarding hepatic effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. Liver pathology has been demonstrated in rats exposed orally to lethal or near lethal doses (e.g., 70% lethal dose) of trans-1,2-dichloroethene. At 1,130 mg/kg/day of trans-1,2-dichloroethene, 2 of 10 rats had severe fatty infiltration of the liver lobules and Kupffer cells; however, these effects were not seen in the rats given higher doses (Freundt et al. 1977). The pathology is similar to that observed in rats exposed by the inhalation route (i.e., fatty degeneration of the Kupffer cells and liver lobules) (Freundt et al. 1977). However, for oral exposure, the effects occurred only after exposure to lethal dose levels. As shown in Table 2-2 and Figure 2-2, repeated exposure to lower levels of trans-1,2-dichloroethene in drinking water for 90 days was tolerated by mice and did not result in liver pathology. However, at 175 mg/kg/day increased serum alkaline phosphatase was seen, indicating some degree of hepatic damage (Barnes et al. 1985). McMillan (1986) examined the hepatic toxicity of cis- and trans-1,2-dichloroethene in rats after oral and intraperitoneal administration, respectively. At an exposure level of 4,400 mg/kg (single dose) of trans-1,2-dichloroethene, a significant increase in plasma alanine aminotransferase was noted, and at 2,500 mg/kg (single dose) of cis-1,2-dichloroethene, a significant increase in plasma sorbitol dehydrogenase activity was noted. Intermediate exposure (30 days) did not result in any treatment- related lesions in the liver. However, significantly elevated liver weights were noted at 480 mg/kg/day of a mixture of the cis and trans isomers for 30 days. Biochemical changes in the liver have been reported in mice and rats exposed to cis- and trans-1,2-dichloroethene (Barnes et al. 1985; Jenkins et al. 1972). However, a connection between these biochemical changes and the pathology or impaired liver function has not been established. As such, the effects can not be classified as adverse or as being indicative of liver toxicity. Changes in hepatic alkaline phosphatase, tyrosine transaminase, glucose-6-phosphatase, and plasma alanine transaminase activities have been observed in rats exposed to single oral doses of 400 or 1,500 mg/kg 1,2-DICHLOROETHENE 32 2. HEALTH EFFECTS of cis- or trans-1,2-dichloroethene (Jenkins et al. 1972). Although the changes observed in these enzyme activities were significant, the validity of the study is limited by the lack of dose-related patterns of the changes, the use of only three or four rats per treatment group, and the lack of reporting of animal responses to dosing. A dose-related decrease in the levels of serum glutamic- oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) was observed in female mice exposed to 23-452 mg/kg/day of trans-1,2-dichloroethene in the drinking water for 90 days (Barnes et al. 1985). Increased serum levels of these hepatic enzymes are usually indicative of liver damage; the toxicological significance of decreased levels is unknown. Increased serum alkaline phosphatase and increased relative liver weights were seen in male mice exposed to 175 mg/kg/day of trans-1,2-dichloroethene for 90 days. No such effects were noted in female mice. Based on a NOAEL of 17 mg/kg/day, an intermediate-duration oral MRL for trans-1,2-dichloroethene of 0.2 mg/kg/day was calculated as described in the footnote to Table 2-2 and in Appendix A. The effect of 90-day exposure to trans-1,2-dichloroethene (17-452 mg/kg/day in drinking water) on hepatic microsomal drug metabolism was assessed by Barnes et al. (1985). In contrast to findings with inhalation exposure studies, oral exposure to trans-1,2-dichloroethene had no effect on the duration of hexobarbital-induced narcosis. In addition, no significant changes were found in hepatic microsomal cytochrome P-450 or cytochrome bs specific content. However, a decrease in microsomal aniline hydroxylase activity was reported in all exposed groups. A significant decrease in hepatic glutathione levels occurred in males after 90 days of exposure to 387 mg/kg/day. A dose-related increase in relative liver weight was observed in rats exposed for 14 and 90 days to cis-1,2-dichloroethene (McCauley et al. 1990). In the 90-day study, effects were significant at 97 mg/kg/day and above. Slight increases in serum cholesterol were observed in the female rats in the 14-day study, and slight decreases in SGOT were observed in the 90-day study. The increased liver weight and biochemical changes cannot be considered adverse because they were not associated with histopathological liver lesions. Renal Effects. No studies were located regarding renal effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. The effects of 1,2-dichloroethene on the kidney have not been examined extensively in laboratory animals. The few studies that have been reported provide evidence to suggest that the kidney is 1,2-DICHLOROETHENE 33 2. HEALTH EFFECTS probably not a primary target for toxicity of trans-1,2-dichloroethene. As presented in Table 2-2 and Figure 2-2, animals tolerated repeated exposure to trans-1,2-dichloroethene in drinking water without adverse effects on the kidney. A dose-related increase in absolute and relative kidney weight occurred in female rats treated with trans-1,2-dichloroethene for 90 days, but no histopathological lesions were identified (Hayes et al. 1987). No detectable chemically-induced changes in blood urea nitrogen or serum creatinine levels were found in animals exposed to trans-1,2-dichloroethene in either the 14-day or 90-day exposure study (Barnes et al. 1985; Hayes et al. 1987). A significant increase in rat kidney weight was reported from a 14-day oral exposure to a 50% mixture of the 1,2-dichloroethene isomers (480 mg/kg/day) (McMillan 1986). An increase in absolute and relative kidney weight, along with a decrease in blood urea nitrogen, was also found in female rats exposed for 14 days to 970 mg/kg/day of cis-1,2-dichloroethene, and in male rats orally exposed to 1,900 mg/kg/day of cis-1,2-dichloroethene (McCauley et al. 1990). However, these changes did not occur in female rats exposed to 870 mg/kg/day of the cis isomer or less for 90 days. In male rats exposed to 870 mg/kg/day of cis-1,2-dichloroethene for 90 days, a significant increase in relative kidney weight and decreases in blood urea nitrogen and creatinine levels occurred. No changes occurred in males exposed to 1,900 mg/kg/day or less for 14 days. The toxicological significance of decreased blood urea nitrogen and creatinine levels is not clear since increases in these parameters are usually associated with renal toxicity. Furthermore, no histological evidence of kidney pathology was observed. In the absence of histological and clinical evidence of renal toxicity, the toxicological significance of the increased kidney weight is not known. Endocrine Effects. No studies were located regarding endocrine effects in humans following oral exposure to cis-or trans-1,2-dichloroethene. Histological examination revealed no compound-related effects in the thyroid in rats exposed to cis-1,2-dichloroethene at doses up to 1,900 or 870 mg/kg/day for 14 or 90 days, respectively (McCauley et al. 1990). Dermal Effects. No studies were located regarding dermal effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. 1,2-DICHLOROETHENE 34 2. HEALTH EFFECTS Histological examination revealed no compound-related effects on the skin of rats exposed to cis-1,2-dichloroethene at doses up to 1,900 or 870 mg/kg/day for 14 or 90 days, respectively (McCauley et al. 1990). Body Weight Effects. No studies were located regarding body weight effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. Body weight was not altered either by 21 or 210 mg/kg/day of trans-1,2-dichloroethene administered for 14 days to mice by gavage (Barnes et al. 1985). In rats, body weight was not altered by a 14-day exposure to a 50% mixture of the 1,2-dichloroethene isomers (480 mg/kg/day) (McMillan 1986), nor by exposure to trans-1,2-dichloroethene (353-3,114 mg/kg/day) in drinking water for 90 days (Hayes et al. 1987). Significant changes in body weight gain were observed in both male and female rats treated with cis-1,2-dichloroethene for 14 days (McCauley et al. 1990). The changes were not dose-related; increased body weight gain occurred at 97 and 290 mg/kg/day and decreased body weight gain occurred at 970 and 1,900 mg/kg/day. The toxicological significance of these binodal body weight changes over a 14-day treatment period is not clear, although it could be due to decreased food intake at higher doses. In the 90-day study, only the male rats receiving the highest dose of cis-1,2-dichloroethene (870 mg/kg/day) had significantly decreased body weight gain when compared with control males. Other Systemic Effects. No studies were located regarding other systemic effects in humans following oral exposure to cis-or trans-1,2-dichloroethene. In female rats, a significant increase in water consumption was seen at 97 mg/kg/day. The authors stated that since cis-1,2-dichloroethene was administered by gavage, this effect must be considered to be compound-related and not associated with water palatability. They additionally noted that determining whether this effect is related to the compound’s influence on the renal, central nervous system, or other organ system will require more data (McCauley et al. 1990). 2.2.2.3 Immunological and Lymphoreticular Effects No studies were located regarding immunological effects in humans following oral exposure to cis- or trans- 1,2-dichloroethene. 1,2-DICHLOROETHENE 35 2. HEALTH EFFECTS The effect of orally-administered trans-1,2-dichloroethene on the immune system has been investigated in rats and mice. No effects were seen on the spleen (Freundt et al. 1977; McCauley et al. 1990) or on leukocyte counts (Barnes et al. 1985; McMillan 1986; Munson et al. 1982) in rats or mice. Barnes et al. (1985) reported increased leukocyte count and decreased relative thymus weight in female mice exposed to 224 mg/kg/day of trans-1,2-dichloroethene for 90 days. Mice exposed to trans-1,2-dichloroethene (up to 220 mg/kg/day by gavage) for 14 days showed no significant changes in cell-mediated or humoral immunity (Munson et al. 1982; Shopp et al. 1985). Repeated exposure of mice to trans-1,2-dichloroethene in drinking water for 90 days had no effect on the cell-mediated immune status of either sex or on the humoral immune status of females (Shopp et al. 1985). A suppression in humoral immune status, as measured by spleen cell antibody production directed against sheep erythrocytes, was observed in male mice treated with each of three doses (17, 175, and 387 mg/kg/day) of trans-1,2-dichloroethene. Although the suppression was significant, it was not severe enough to depress the functional ability of the humoral immune system, as indicated by a normal spleen cell response to B cell mitogen lipopolysaccharide and normal hemagglutination titers. The highest NOAEL values for immunological effects in mice in each duration category are recorded in Table 2-2 and plotted in Figure 2-2. Immunological effects were noted from exposure to 1,900 mg/kg/day of cis-1,2-dichloroethene in rats for 14 days, while an increase in absolute and relative thymus weights was noted in female rats exposed to 870 mg/kg/day for 90 days (McCauley et al. 1990). 2.2.2.4 Neurological Effects No studies were located regarding neurological effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. The neurological effects of cis- and trans-1,2-dichloroethene in animals have not been extensively examined, though acute exposure and stimuli/response research do provide insight. Signs of central nervous system depression have been observed in rats and mice at the terminal stages after receiving lethal doses of cis- and trans-1,2-dichloroethene (Barnes et al. 1985; Hayes et al. 1987; McCauley et al. 1990). Central nervous system depression (not further specified) was reported in rats treated with cis-1,2-dichloroethene at 1,900 mg/kg/day for 14 days (McCauley et al. 1990). The highest NOAEL 1,2-DICHLOROETHENE 36 2. HEALTH EFFECTS value and the LOAEL values from each reliable study with neurological end points are presented in Table 2-2 and plotted in Figure 2-2. Dose-related conditioned taste aversion to saccharin was produced in mice exposed to a mixture of cis- and trans-1,2-dichloroethene (Kallman et al. 1983). This neurobehavioral test will detect both neurological and non-neurological effects that are perceived by the test animal to be adverse. The nature of the adverse stimuli that results in taste aversion has not been identified. 2.2.2.5 Reproductive Effects No studies were located regarding reproductive effects in humans following oral exposure to cis- or trans-1,2-dichloroethene. Neither acute nor intermediate exposures (14 and 90 days) have caused histological changes in reproductive organs of rats exposed to levels of cis-1,2-dichloroethene up to 1,900 mg/kg/day (McCauley et al. 1990). Rats exposed by gavage showed no treatment-related lesions in mammary glands, clitoral glands, ovaries, uterus, seminal vesicles, prostate, testes or preputial glands. No treatment-related histopathological lesions in the reproductive organs were seen in rats exposed to trans-1,2-dichloroethene for up to 90 days (Barnes et al. 1985; Hayes et al. 1987). No studies were located regarding the following effects in humans or animals following oral exposure to cis- or trans-1,2-dichloroethene: 2.2.2.6 Developmental Effects 2.2.2.7 Genotoxic Effects Genotoxicity studies are discussed in Section 2.5. 2.2.2.8 Cancer 1,2-DICHLOROETHENE 37 2. HEALTH EFFECTS 2.2.3 Dermal Exposure 2.2.3.1 Death No studies were located regarding lethal effects in humans following dermal exposure to cis- or trans-1,2-dichloroethene. No deaths were reported from application of trans-1,2-dichloroethene at 5,000 mg/kg body weight on clipped, intact skin of 2 male and 3 female rabbits (Brock 1990). Table 2-3 summarizes the significant dermal exposure studies, presenting the highest NOAEL values and all LOAEL values from each important study. No studies were located regarding lethal effects in animals following dermal exposure to cis-1,2-dichloroethene. 2.2.3.2 Systemic Effects No dermal exposure studies of cis- or trans-1,2-dichloroethene were located regarding respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, or endocrine effects in humans or animals. Dermal Effects. No studies were located regarding dermal effects in humans following dermal exposure to cis- or trans-1,2-dichloroethene. Dermal effects have been shown in laboratory animals exposed dermally to trans-1,2-dichloroethene. Application of 170 mg/kg (0.5 mL) of trans-1,2-dichloroethene for 24 hours to clipped, intact skin of 1 female and 5 male rabbits under an occlusive wrapping produced mild or moderate erythema at all observation times (24, 48 and 72 hours) (Brock 1990). In a separate experiment (Brock 1990), 5,000 mg/kg of trans-1,2-dichloroethene was applied to the clipped, intact skin of 2 male and 3 female rabbits. Severe dermal irritation was observed, but no clinical signs of toxicity other than body weight loss were found. No studies were located regarding dermal effects in animals following dermal exposure to cis-1,2-dichloroethene. Table 2-3. Levels of Significant Exposure to 1,2-Dichloroethene - Dermal Exposure/ Duration/ LOAEL Species Frequency System NOAEL Less Serious Serious Reference (Strain) {Spiacitic Chemical Form Route) ACUTE EXPOSURE Systemic Human 5-30 min Ocular 280M 830 M (slight burning of eyes) Lehmann and (aitbome) ppm ppm Schmidt-Kehl 1936 trans Rat 10d Dermal 12000 F Hurtt et al. 1993 (cr: coBr) Gd 7-16 ppm trans 6 hr/d Ocular 2000 F (lacrimation) (airbome) ppm Rabbit 20 sec Ocular 3.3 F (transient severe corneal Brock 1990 (New Zealand (eyes) mg/kg opacity, moderate iritis, and trans White) conjunctivitis) Rabbit 24 hr Dermal 170 (mild or moderate Brock 1990 (NS) mg/kg erythema) Abstract trans Rabbit 24 hr Dermal 5000 (severe dermal irritation) Brock 1990 (NS) mg/kg Abstract trans Bd Wt 5000 (body weight loss not mg/kg otherwise specified) Bd Wt = body weight; d = day(s); F = female; Gd = gestational day; hr = hour(s); LOAEL = lowest-observable-adverse-effect level; M = male; min = minute(s); NOAEL = no-observable-adverse-effect level; NS = not specified; sec = second(s) S103443 H1TV3H 2 INIHL3OHOTHOIa-2 + 8€ 1,2-DICHLOROETHENE 39 2. HEALTH EFFECTS Ocular Effects. An early study by Lehmann and Schmidt-Kehl (1936) reported a slight burning of the eyes in two human subjects exposed for 30 minutes to concentrations between 830 and 2,220 ppm of trans-1,2-dichloroethene in air. The subjects were exposed under controlled conditions, not as an occupational accident. It is not certain whether the subjects were exposed to a vapor or to an aerosol of this chemical. The accuracy of the reported exposure levels is questionable because of the insensitivity of the methods used in 1936 to measure the concentration of 1,2-dichloroethene in air. Also, the degree of purity of the trans isomer used is uncertain. No studies were located regarding ocular effects in humans following dermal exposure to cis-1,2-dichloroethene. Severe corneal opacity, moderate iritis, conjunctivitis and lacrimation have been shown in rats after direct eye exposure to trans-1,2-dichloroethene. Trans-1,2-dichloroethene (0.01 mL) was placed in the lower conjunctival sac of two female rabbits and 20 seconds later, the eyes of one rabbit were washed with tap water while the eyes of the other rabbit remained unwashed. Severe corneal opacity was observed in the washed eye and moderate iritis and conjunctivitis were observed in both treated eyes; however, all irritation was resolved by day 3 (Brock 1990). Airborne exposure to trans-1,2-dichloro- ethene caused lacrimation in rats at 2,000 ppm (Hurtt et al. 1993). No studies were located regarding ocular effects in animals following dermal exposure to cis-1,2-dichloroethene. Body Weight Effects. No studies were located regarding body weight effects in humans following dermal exposure to cis- or trans-1,2-dichloroethene. Brock (1990) applied 5,000 mg/kg trans-1,2-dichloroethene to the clipped, intact skin of 2 male and 3 female rabbits. Loss of body weight (amount unspecified) was observed. No studies were located regarding body weight effects in animals following dermal exposure to cis-1,2-dichloroethene. 1,2-DICHLOROETHENE 40 2. HEALTH EFFECTS No studies were located regarding the following effects in humans or animals following dermal exposure to cis- or trans-1,2-dichloroethene: 2.2.3.3 Immunological and Lymphoreticular Effects 2.2.3.4 Neurological Effects 2.2.3.5 Reproductive Effects 2.2.3.6 Developmental Effects 2.2.3.7 Genotoxic Effects Genotoxicity studies are discussed in Section 2.5. 2.2.3.8 Cancer 2.3 TOXICOKINETICS 1,2-Dichloroethene appears to be absorbed quickly by the lungs. One study reported that approximately 75% of the inhaled chemical was absorbed through the lungs in humans. 1,2-Dichloroethene is metabolized in the liver, by hepatic microsomal cytochrome P-450, to form dichloroethanol and dichloroacetic acid. Animal studies have shown that metabolism of the cis isomer occurs faster than metabolism of the trans isomer, and the cis isomer frequently inhibits activity or destroys cytochrome P-450 levels, while the trans isomer frequently increases the enzyme levels. No information is available on the excretion of 1,2-dichloroethene in humans or animals. 2.3.1 Absorption 2.3.1.1 Inhalation Exposure In tests for partitioning between human blood and air (Gargas et al. 1989), the results show a relatively high affinity of 1,2-dichloroethene for blood (cis-1,2-dichloroethene - blood:air partition coefficient = 1,2-DICHLOROETHENE 41 2. HEALTH EFFECTS 9.58 [+0.70] and trans-1,2-dichloroethene = 6.04 [£0.38]). Several other studies appear to support the conclusion that 1,2-dichloroethene is absorbed relatively quickly by the lungs. Sato and Nakajima (1979) reported blood:air partition coefficients (ratio concentrations in blood and air at 37 °C) of 9.2 and 5.8 for cis and trans isomers of 1,2-dichloroethene, respectively. Both isomers of 1,2-dichloro- ethene in inspired air achieve an equilibrium with the whole animal within 1.5-2 hours (Filser and Bolt 1979). Gargas et al. (1988, 1989) determined liquid:air and tissue:air partition coefficients for cis- and trans-1,2-dichloroethene. Partition coefficients were determined with 0.9% saline; olive oil; and blood, liver, muscle, and fat tissues from rats. The partition coefficients for cis-1,2-dichloroethene are: blood = 21.6 (2.0), 0.9% saline = 3.25 (40.12), olive oil = 278 (£6), fat = 227 (£11), liver = 15.3 (£1.1), and muscle = 6.09 (£1.02). The coefficients for trans-1,2-dichloroethene are: blood = 9.58 (£0.94), 0.9% saline = 1.41 (£0.04), olive oil = 178 (16), fat = 148 (£11), liver = 8.96 (30.61), and muscle = 3.52 (£0.54). Lehmann and Schmidt-Kehl (1936) reported that 72-75% of inhaled trans-1,2-dichloroethene is absorbed through the lungs in humans. Further insight is provided by Anderson et al. (1980), who reported that trans-1,2-dichloroethene follows mixed-form uptake kinetics, with a composite of a slow first-order and a saturable uptake process. No studies were located regarding the rate and extent of cis- or trans-1,2-dichloroethene absorption for the following: 2.3.1.2 Oral Exposure 2.3.1.3 Dermal Exposure 2.3.2 Distribution No studies were located regarding the distribution of cis- and trans-1,2-dichloroethene following exposure by any routes. 2.3.3 Metabolism Metabolism of 1,2-dichloroethene is initially catalyzed by hepatic microsomal cytochrome P-450 (Costa and Ivanetich 1982, 1984). Although there is no direct evidence, studies on the synthesis of the epoxides suggest that this metabolism involves epoxidation of the ethylene double bond, forming 1,2-DICHLOROETHENE 42 2. HEALTH EFFECTS dichlorinated epoxides (Figure 2-3). Dichlorinated epoxides, in turn, can undergo a non-enzymatic rearrangement. Studies on the metabolism of 1,2-dichloroethene by hepatic microsomes and hepatocytes provide evidence to suggest that dichloroacetaldehyde is the predominant metabolite of microsomal cytochrome P-450 and that it, in turn, is extensively converted to dichloroethanol and dichloroacetate by cytosolic and/or mitochondrial aldehyde and alcohol dehydrogenases present in hepatocytes (Costa and Ivanetich 1982, 1984; Leibman and Ortiz 1977). This is consistent with the report that both the cis and trans isomers of 1,2-dichloroethene were converted to dichloroethanol and dichloroacetic acid by perfused rat liver (Bonse et al. 1975). Similarities and differences have been observed in the metabolism of cis- and trans-1,2-dichloroethene. Both isomers have been shown to bind to the active site of hepatic cytochrome P-450 (Costa and Ivanetich 1982). In addition, classic inhibitors of cytochrome P-450 have been shown to inhibit the production of dichloroacetaldehyde from both isomers. The binding and metabolism of 1,2-dichloro- ethene do not appear to be specific for any one form of cytochrome P-450. The cis isomer had a 4-fold greater rate of turnover in hepatic microsomes in vitro than the trans isomer. This is consistent with studies on isolated perfused rat livers, where metabolism of the cis isomer occurred at a greater rate than metabolism of the trans isomer (Bonse et al. 1975). In addition, differences between cis- and trans-1,2-dichloroethene in the rates of formation of dichloroethanol and dichloroacetic acid have been reported in rat hepatocytes (Costa and Ivanetich 1984). Several reports suggest that 1,2-dichloroethene can alter cytochrome P-450 and mixed-function oxidase activities. McMillan (1986) reported depression of cytochrome P-450 dependent microsomal metabolism by both isomers of 1,2-dichloroethene, while Paolini et al. (1992) reported the induction of cytochrome P-450 enzymes by trans-1,2-dichloroethene. Freundt and Macholz (1978) demonstrated that each of the isomers of 1,2-dichloroethene competitively inhibited the metabolism of hexobarbital in vivo following a single 8-hour inhalation exposure of rats to 200 ppm of these isomers. The effects of the cis isomer were more potent than those of the trans isomer. In addition, trans-1,2-dichloro- ethene competitively inhibited the oxidative N-demethylation of aminopyrine and the O-demethylation of p-nitroanisole by hepatic microsomes. Bronzetti et al. (1984) demonstrated that an intraperitoneal injection of the trans isomer can increase cytochrome P-450 levels (consistent with the work of Paolini 1992) and aminopyrine N-demethylase activity in mice, while injection of the cis isomer more frequently tended to inhibit activity or destroy the enzyme. trans-1,2-DCE Figure 2-3. Postulated Metabolic Scheme for 1,2-Dichloroethene ON | I | _o 40 H—G—C. H—C—C_ AN OH cl Cl cl Monochloro- Monochloro- acetyl chloride acetic acid H O H NN H—g—3—on / A H 0 cl cl V4 Cl~C~=C ©) | h" J / Fe S + ci OH c=4 | 2,2-Dichloroacetic acid cl H 0 oN H 0 Cyt P-450 «| oxide 4 — > fee Git imme ff Cl—C—=C H H 0 \ 7 2 Cad NADPH cc Sl HA \ ®, cl cl 2,2-Dichloro- Ley, acetaldehyde 7 H OH cis-1,2-DCE I Cl—C—C—H Cl H Dichloroethanol Adapted from Costa and Ivanetich 1982 S103443 HLTV3H ¢ INIHL3OHOHOIa-2't £v 1,2-DICHLOROETHENE 44 2. HEALTH EFFECTS The metabolic elimination of 1,2-dichloroethene has been described as a saturable, dose-dependent process (Filser and Bolt 1979). In rats exposed to atmospheric concentrations of 1,2-dichloroethene that exceed a "point of saturation," elimination proceeds by zero-order kinetics (rate independent of the concentration of the compound); below saturation, first-order kinetics apply (Filser and Bolt 1979). Pharmacokinetic studies on 1,2-dichloroethene elimination in the gas phase of a closed inhalation exposure system show that cis-1,2-dichloroethene has a higher rate of first-order clearance than the trans isomer. The cis isomer also exhibits a higher rate of metabolic elimination under saturation conditions, in comparison to the trans isomer. This observation is consistent with the higher rate of metabolism of the cis isomer relative to the trans isomer by rat liver microsomes (Costa and Ivanetich 1982) and by isolated perfused liver (Bonse et al. 1975). 2.3.4 Excretion No studies were located regarding the excretion of 1,2-dichloroethene in humans or animals following exposure by any routes. 2.4 MECHANISMS OF ACTION Both cis- and trans-1,2-dichloroethene are volatile, lipophilic molecules that easily move through the respiratory and gastrointestinal systems. Based on their molecular size and lipophilicity, they probably pass through membranes by simple (passive) diffusion. Toxicokinetic evidence shows they have a high affinity for lipids and blood, but little accumulation in tissues. Both the cis and trans isomers of 1,2-dichloroethene are converted to dichloroethanol and dichloroacetic acid by rat liver (Bonse et al. 1975), with the cis isomer exhibiting a higher rate of metabolism than the trans isomer (Costa and Ivanetich 1982). 1,2-Dichloroethene isomers inhibit liver enzymes involved in metabolism and may increase the "toxic" response to other chemicals (Bolt et al. 1980; McMillan 1986). Reactive metabolites of 1,2-dichloro- ethene modify the heme moiety of hepatic microsomal cytochrome P-450, resulting in a loss of both cytochrome P-450 and heme (Costa and Ivanetich 1982). This modification could account for the observed in vivo and in vitro inhibition of other cytochrome P-450 substances by 1,2-dichloroethene. Compounds, such as carbon monoxide, that inactivate or inhibit the cytochrome P-450 system, should 1,2-DICHLOROETHENE 45 2. HEALTH EFFECTS also inhibit the metabolism of 1,2-dichloroethene. 1,2-Dichloroethene is oxidized to its epoxide, which is relatively stable (Bolt et al. 1980). Its lack of genotoxicity is related to this stability. The differences in metabolism, and possibly toxicity, between the cis and trans isomers have been partially explained by differences in the stereochemistry of the epoxides formed. The asymmetrical metabolites appear to be more electrophilic and also more mutagenic (Greim et al. 1975; Henschler 1977). The cis isomer is more actively metabolized than the trans isomer, because the trans isomer is a more stable form and the proximity of the two chlorine atoms in the cis isomer increases the binding to other molecules with which it reacts (Henschler 1977). Physiologically based pharmacokinetic modeling (PBPK) has been used to explain metabolic rates for 1,2-dichloroethene. A model that included suicide enzyme inhibition-resynthesis has been used to describe the metabolism of 1,2-dichloroethene in the rat (Gargas et al. 1990). In this model, metabolism results in the inactivation of cytochrome P-450, which could result in an increase or decrease in the toxicity of 1,2-dichloroethene. 2.5 RELEVANCE TO PUBLIC HEALTH Inhalation, oral, and dermal routes of exposure to 1,2-dichloroethene are of concern to humans because 1,2-dichloroethene has been found in air, drinking water, and soil (Shah and Singh 1988; Westrick et al. 1984; VIAR 1987). Toxicokinetic data are very limited for both human and animal exposures. Partition coefficients suggest that 1,2-dichloroethene has a much stronger affinity for blood and fats than for air. Although the compound is relatively lipophilic, there is no good evidence for accumulation in important organs such as liver, brain, kidney, and adipose tissue. Tissue saturation should not be found at anticipated exposure levels. 1,2-Dichloroethene is likely to be metabolized to more hydrophilic by-products, and, therefore, eliminated quickly by the kidneys as metabolites. The most significant effects of 1,2-dichloroethene exposure are hematological and hepatic. At high levels of exposure, clinical symptoms that have been reported in humans exposed to 1,2-dichloroethene in air include nausea, drowsiness, fatigue, intracranial pressure and ocular irritation. One fatality has been reported. No information is available on oral toxicity for 1,2-dichloroethene in humans. No information is available on the relative toxicities of the cis and trans isomers of 1,2-dichloroethene in humans. 1,2-DICHLOROETHENE 46 2. HEALTH EFFECTS Pathological lesions of the heart, liver, and lungs have been reported in rats exposed to trans-1,2-dichloroethene in air. Ataxia and respiratory depression occur in the terminal stages prior to death in animals. Since these conditions have not been observed in humans, their relevance to public health is not known. A variety of genotoxicity tests have been performed for 1,2-dichloroethene. The predominant results are negative, and no carcinogenicity studies were found in the literature. Federal and international agencies have given 1,2-dichloroethene a non-cancer rating or a "not classifiable" rating. Minimal Risk Levels for 1,2-Dichloroethene. MRLs have been derived for acute and intermediate exposure to the cis and trans isomers of 1,2-dichloroethene; no chronic studies are available from which to derive MRLs for chronic exposure. The derivation of each MRL is discussed fully in Appendix A. Inhalation MRLs. * An MRL of 0.2 ppm has been derived for acute-duration exposure (14 days or less) and for intermediate-duration inhalation exposure (15-364 days) to trans-1,2-dichloroethene. The acute MRL is based on a LOAEL of 200 ppm for trans-1,2-dichloroethene over an 8-hour period that caused fatty degeneration of the liver (Freundt et al. 1977). Longer periods of exposure at 200 ppm showed increased numbers and severity of response. The intermediate MRL is based on the same study and effects (Freundt et al. 1977) in which rats were exposed to 200 ppm trans-1,2-dichloroethene for 8 hours per day, 5 days per week for 8 or 16 weeks. An uncertainty factor of 1,000 is used: 10 for using a LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability. No chronic inhalation MRL has been derived for trans-1,2-dichloroethene because no study tested 1,2-dichloroethene for a sufficiently long period of time. No acute-, intermediate- or chronic-duration MRLs have been derived for cis-1,2-dichloroethene because of lack of data. 1,2-DICHLOROETHENE 47 2. HEALTH EFFECTS Oral MRLs. Studies of oral exposure to 1,2-dichloroethene exist to develop oral MRLs for both the cis and trans Isomers. ¢ An MRL of 1 mg/kg/day has been derived for acute-duration oral exposure (14 days or less) to cis-1,2-dichloroethene. This MRL for the cis isomer is based on a NOAEL of 97 mg/kg/day for decreased red blood cell counts and hematocrit levels in female rats exposed to 97 mg/kg/day cis-1,2-dichloroethene for 14 days (McCauley et al. 1990). An uncertainty factor of 100 is used: 10 for extrapolation from animals to humans, and 10 for human variability. Hematological effects have also been noted in other oral studies (Barnes et al. 1985). No acute oral MRL has been derived for trans-1,2-dichloroethene. Separate intermediate-duration oral MRLs were derived for exposure to the cis and trans isomers. ¢ An MRL of 0.3 mg/kg/day has been derived for intermediate-duration oral exposure to 1,2-DICHLOROETHENE 48 2. HEALTH EFFECTS al. 1985). An uncertainty factor of 100 was developed for the MRL, using factors of 10 for animal-to- human extrapolation and 10 to protect sensitive individuals. In this study, serum alkaline phosphatase levels were significantly increased. Though the two highest doses caused increased serum alkaline phosphatase levels in a non-dose-related manner, the effects are consistent with the fatty accumulation in hepatocytes. This hepatic intermediate end point is slightly lower than a hematological NOAEL (decreased hematocrit). Other organs and end points were an order of magnitude less sensitive to cis-1,2-dichloroethene than were hepatic and hematologic target organs. Death. A fatality was reported to have occurred after inhalation of 1,2-dichloroethene in a small enclosure (Hamilton 1934). Details regarding the exposure levels (cis and trans) in this accident and the cause of death are not available. No reports of lethality related to oral exposure of humans to 1,2-dichloroethene were located. Terminal symptoms in animals exposed orally to cis- or trans-1,2-dichloroethene involve central nervous system depression (e.g., ataxia and loss of righting reflex) and respiratory depression (Barnes et al. 1985; Hayes et al. 1987; McCauley et al. 1990; Munson et al. 1982). Results of studies in which animals have inhaled or ingested trans-1,2,-dichloroethene implicate the heart, liver, and lung as potential targets for toxicity (Barnes et al. 1985; Freundt et al. 1977; Hayes et al. 1987; McMillan 1986). The relative lethal potency of the cis and trans isomers to each other is not known. Systemic Effects. Trans-1,2-dichloroethene appears to be an ocular irritant in humans. Two human participants in a self-experimentation study reported mild burning of the eyes after acute exposure to either vapors or aerosols of trans-1,2-dichloroethene (Lehmann and Schmidt-Kehl 1936). No other specific systemic effects have been reported in humans. Cis-1,2-dichloroethene may induce a similar toxicological effect; however, no reports were located that specifically implicated cis- 1,2-dichloroethene as an ocular irritant. Systemic effects involving the heart, liver, and lungs have been observed in animals exposed to trans-1,2-dichloroethene. Evidence for serious adverse effects in these organs consists of only one study (Freundt et al. 1977). Effects reported in the rat include lung lesions (hyperemia and alveolar septal distension), fibrous swelling of the myocardium, and fatty degeneration of the liver. All three effects were observed after inhalation exposures to trans-1,2-dichloroethene at concentrations of 200 ppm or greater for 8 hours. Liver and lung lesions were observed after gavage dosing, but only 1,2-DICHLOROETHENE 49 2. HEALTH EFFECTS after near lethal doses were administered. The treatment groups in this study were too small to establish a high degree of confidence in these findings. However, one additional serious systemic effect was found in rats—reduced weight gain for pregnant dams exposed to airborne 1,2-dichloro- ethene (Hurtt et al. 1993). Exposure of rats (Hayes et al. 1987) or mice (Barnes et al. 1985) to trans-1,2-dichloroethene at doses up to 3,114 mg/kg/day, in the drinking water for 90 days, did not result in adverse systemic effects. Increased liver and kidney weights were observed in rats treated orally with cis-1,2-dichloroethene for 14 or 90 days, but these increased organ weights were not accompanied by any histopathological lesions in either organ (McCauley et al. 1990). Rats exposed to the cis isomer by gavage for 14 and 90 days showed a dose-related decrease in red blood cell count and hematocrit levels (McCauley et al. 1990). Hematotoxicity was not observed in mice or rats exposed to the trans isomer (Barnes et al. 1985; Hayes et al. 1987). The different results in the rat studies could be due to differential toxicity between the two isomers, as well as to other factors, including initial age of the rats, vehicle differences, and different exposure methods. Hayes et al. (1987) exposed rats with an initial age of 26 days to the trans isomer in a 1% emulphor drinking water suspension, while McCauley et al. (1990) treated rats with an initial age of 70 days with the cis isomer in corn oil by gavage. Data regarding toxic systemic effects of 1,2-dichloroethene in animals are too limited to draw any conclusions for human exposure. Respiratory Effects. Pulmonary effects of inhalation and oral exposure to 1,2-dichloroethene have been shown over a range of exposure levels and for both inhalation and oral routes. No effect levels are reported from 485 to 2,000 mg/kg/day; however, several studies found pronounced respiratory effects around 1,000 mg/kg/day or 1,000 ppm (Freundt et al. 1977; McCauley et al. 1990; McMillan 1986). All these values are relatively high. Cardiovascular Effects. The likelihood of acute exposure to 1,2-dichloroethene is quite small. Only at high levels (3,000 ppm or 1,100 mg/kg/day) is there animal evidence of swelling of heart muscle and congestion of blood in and near the heart (Freundt et al. 1977). Hematological Effects. There are known blood effects of 1,2-dichloroethene, but these occur at exposure levels above those expected for the general population. Acute- and intermediate-exposure hematologic studies are the bases for oral MRLs for cis-1,2-dichloroethene (McCauley et al. 1990). 1,2-DICHLOROETHENE 50 2. HEALTH EFFECTS Musculoskeletal Effects. Animal studies have not reported effects on the musculoskeletal system (Freundt et al. 1977; McCauley et al. 1990). Thus, it does not appear that musculoskeletal effects are of concern for human exposure to 1,2-dichloroethene. Hepatic Effects. Liver effects in animals include fatty degeneration of liver lobules; such effects are reasonable to anticipate among humans, though exposure levels of greater than 100 mg/kg/day are not anticipated. Higher exposure levels produced enzyme changes (decreased serum alkaline phosphatase, serum albumin and blood urea nitrogen or increased plasma enzyme activity) according to some of the available literature (Freundt et al. 1977; McMillan 1986). Acute- and intermediate-exposure hepatic studies are the bases for inhalation MRLs for trans-1,2-dichloroethene (Freundt et al. 1977) and for an oral MRL for trans-1,2-dichloroethene (Barnes et al. 1985). Renal Effects. Reduced kidney function and increased kidney weight are expected with acute high level exposure (McCauley et al. 1990; McMillan 1986); however, the public health concern is relatively small because such effects are not known to occur at chronic lower level exposure. Dermal Effects. Acute exposure of the skin causes effects that are readily reversible. Irritation and mild effects on skin are the most frequent effects likely to be observed (Brock 1990). Ocular Effects. Acute exposure causes readily reversible effects such as a slight burning of the eyes (Lehman and Schmidt-Kehl 1936). Body Weight Effects. Acute- and intermediate-duration exposure has affected weight gain in pregnant and young rats (Hurtt et al. 1993; McCauley et al. 1990). In pregnant rats, reduced food consumption was observed along with reduced weight gain. Intermediate oral exposure caused smaller weight gains for growing rats. Immunological and Lymphoreticular Effects. There are no reports of immunological effects in humans as a result of exposure to cis- or trans-1,2-dichloroethene by any route. Studies in rats and mice have not shown effects on the spleen, leukocytes, or liver Kupffer cells (Barnes et al. 1985; Freundt et al. 1977; McMillan 1986; Munson et al. 1982). Studies in mice have demonstrated perturbations of the humoral immune system (suppressed spleen cell antibody production against sheep erythrocytes) after exposure to trans-1,2-dichloroethene (Shopp et al. 1985). The observed changes in 1,2-DICHLOROETHENE 51 2. HEALTH EFFECTS the humoral immune system did not constitute a functional impairment of the humoral immune response and, therefore, are not considered to be adverse. The data regarding immunological effects of 1,2-dichloroethene in animals are too limited to draw any conclusion about potential immunological effects in humans. Neurological Effects. The central nervous system depressant properties of 1,2-dichloroethene represent an important effect in humans. Dizziness, drowsiness, vertigo, and intracranial pressure are some of the symptoms that have been reported in humans after inhalation of trans-1,2-dichloroethene (Lehmann and Schmidt-Kehl 1936). These symptoms disappeared quickly after exposure was terminated. The pharmacological basis for the 1,2-dichloroethene-mediated narcosis has not been studied. Central nervous system depression (e.g., ataxia, loss of righting reflex) has been observed in some animal studies as well, but only at the terminal stages after the administration of lethal doses of both cis- and trans-1,2-dichloroethene (Hayes et al. 1987; McCauley et al. 1990; Munson et al. 1982). A study in rats and mice reported on the air concentrations evoking a depression in the duration of hindlimb extension (Frantik et al. 1994). A marked species dependent effect was observed in this study. Therefore, it is difficult to draw any conclusions regarding the significance of this type of neurological effect in humans. Reproductive Effects. There are no reports of reproductive effects in humans as a result of exposure to cis- or trans-1,2-dichloroethene by any route. It is not known whether reproductive effects may be of concern to humans. One study showed an increase in resorption rates in rats; however, the authors interpreted this effect as not being treatment related (Hurtt et al. 1993). Developmental Effects. There are no reports of developmental effects in humans as a result of exposure to cis- or trans-1,2-dichloroethene by any route. It is not known whether developmental effects may be of concern to humans. Fetal weights were reduced significantly in a developmental rat study; however, this was probably due to reduced food consumption in the pregnant rats (Hurtt et al. 1993). 1,2-DICHLOROETHENE 52 2. HEALTH EFFECTS Genotoxic Effects. Genotoxic effects of cis- and trans-1,2-dichloroethene in humans are unknown. Mutagenicity of 1,2-dichloroethene has been examined in a variety of test systems. In vivo tests (Table 2-4) indicate that cis-1,2-dichloroethene, but not trans-1,2-dichloroethene, is genotoxic. The cis isomer was found to be mutagenic in the host-mediated assay using a series of Salmonella tester strains in mice (Cerna and Kypenova 1977). Bronzetti et al. (1984) also found that the cis isomer was mutagenic in Saccharomyces cerevisiae D7 in a host-mediated assay in mice, with significant increases in convertants at the trp locus and revertants at the ilv locus. Cantelli-Forti and Bronzetti (1988) also reported that cis-1,2-dichloroethene was mutagenic in the S. cerevisiae D7 strain in mice. Dose-dependent toxicity increased in the presence of the mouse, S9 microsomal fraction. In addition, repeated intraperitoneal injection of cis-1,2-dichloroethene produced chromosomal aberrations in mouse bone marrow cells (Cerna and Kypenova 1977). Negative results were obtained with trans-1,2-dichloroethene in these assays. In vitro tests of genotoxicity of the cis and trans isomers are summarized in Table 2-5. Neither isomer was genotoxic with or without metabolic activation in Escherichia coli K12 (Greim et al. 1975), in several strains of S. typhimurium in spot tests (Cerna and Kypenova 1977; Mortelmans et al. 1986), or in gene mutation and gene conversion tests in S. cerevisiae D7 (Galli et al. 1982). However, Bronzetti et al. (1984) found positive results for gene mutation tests of the cis isomer in S. cerevisiae D7, with metabolic activation. Neither isomer produced chromosomal aberrations or sister chromatid exchanges in Chinese hamster cells (Sawada et al. 1987). The cis isomer, but not the trans isomer, induced unscheduled DNA synthesis in rat hepatocytes (Costa and Ivanetich 1984). Cancer. To date, cancer effects of cis- and trans-1,2-dichloroethene have not been studied in humans or animals. 2.6 BIOMARKERS OF EXPOSURE AND EFFECT Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 1989). Table 2-4. Genotoxicity of cis- and trans-1,2-Dichloroethene In Vivo Species (test system) End point Reference cis-1,2-Dichloroethene Mammalian systems: Mouse bone Host-mediated assays: Salmonella typhimurium (mouse host-mediated assay) Saccharomyces cerevisiae D7 (mouse host-mediated assay) S. cerevisiae D7 (mouse host-mediated assay) trans-1,2-Dichloroethene Mammalian systems: Chromosomal aberrations Host-mediated assays: S. typhimurium (mouse host-mediated assay) S. cerevisiae D7 (mouse host-mediated assay) S. cerevisiae D7 (mouse host-mediated assay) Chromosomal aberrations Gene mutation Gene mutation Gene conversion Mouse bone marrow Gene mutation Gene mutation Gene conversion Cerna and Kypenova 1977 Cerna and Kypenova 1977 Cantelli-Forti and Bronzetti 1988 Bronzetti et al. 1984 Bronzetti et al. 1984 Cantelli-Forti and Bronzetti 1988 Cerna and Kypenova 1977 Cerna and Kypenova 1977 Cantelli-Forti and Bronzetti 1988 Bronzetti et al. 1984 Bronzetti et al. 1984 Cantelli-Forti and Bronzetti 1988 + = positive result; — = negative result S103443 H1IV3H 2 INIHLIOHOTHOIa2 + €S Table 2-5. Genotoxicity of cis- and trans-1,2-Dichloroethene In Vitro Species (test system) End point Result With activation Without activation Reference cis-1,2-Dichloroethene Prokaryotic organisms: Escherichia coli K12 Salmonella typhimurium Eukaryotic organisms: Fungi: Saccharomyces cerevisiae D7 S. cerevisiae D7 Mammalian cells: Chinese hamster CHL cells Chinese hamster CHL cells Rat hepatocytes trans-1,2-Dichloroethene Prokaryotic organisms: E. coli K12 S. typhimurium Gene mutation Gene mutation Gene mutation Gene conversion Chromosomal aberrations Sister chromatic exchange Unscheduled DNA synthesis Gene mutation Gene mutation ND NA ND Greim et al. 1975 Cerna and Kypenova 1977 Mortelmans et al. 1986 Bronzetti et al. 1984 Galli et al. 1982 Galli et al. 1982 Sawada et al. 1987 Sawada et al. 1987 Costa and lvanetich 1984 Greim et al. 1975 Cantelli-Forti and Bronzetti 1988 Cerna and Kypenova 1977 S103443 H1V3H 2 3INIHLIOHOTHOIA-C'} vs Table 2-5. Genotoxicity of cis- and trans-1,2-Dichloroethene In Vitro (continued) Species (test system) trans-1,2-Dichloroethene (continued) Eukaryotic organisms: Fungi: S. cerevisiae D7 S. cerevisiae D7 Mammalian cells: Chinese hamster CHL cells Chinese hamster CHL End point Gene mutation Gene conversion Chromosomal aberrations Sister chromatid exchange With activation Without activation Reference Bronzetti et al. 1984 Galli et al. 1982 Bronzetti et al. 1984 Galli et al. 1982 Sawada et al. 1987 Sawada et al. 1987 Costa and Ivenetich 1984 cells Rat hepatocytes Unscheduled DNA synthesis NA NA = not applicable; ND = no data; — = negative results; + = positive results. S103443 H1V3H 2 3IN3IHL3OHOTHOIQ-2 + SS 1,2-DICHLOROETHENE 56 2. HEALTH EFFECTS Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic substance or its metabolite(s), or the product of an interaction between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a compartment of an organism (NRC 1989). The preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in readily obtainable body fluid(s) or excreta. However, several factors can confound the use and interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures from more than one source. The substance being measured may be a metabolite of another xenobiotic substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as copper, zinc, and selenium). Biomarkers of exposure to 1,2-dichloroethene are discussed in Section 2.6.1. Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an organism that, depending on magnitude, can be recognized as an established or potential health impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung capacity. Note that these markers are not often substance specific. They also may not be directly adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused by 1,2-dichloroethene are discussed in Section 2.6.2. A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are discussed in Section 2.8, Populations That Are Unusually Susceptible. 1,2-DICHLOROETHENE 57 2. HEALTH EFFECTS 2.6.1 Biomarkers Used to Identify or Quantify Exposure to 1,2-Dichloroethene There currently are no biomarkers available to quantify exposure to 1,2-dichloroethene. Methods exist for determining 1,2-dichloroethene in blood and biological tissues (see Chapter 6), but specific levels of 1,2-dichloroethene have not been directly correlated with exposure via any route. Acetonemia and acetone exhalation were observed in rats after inhalation exposure to halogenated ethylenes, including cis- and trans-1,2-dichloroethene (Filser et al. 1978). (Acetone is not a metabolite of 1,2-dichloroethene exposure, but rather may be caused by stimulation of cellular systems that lead to increased acetone production.) Acetone exhalation occurred during exposure of rats to a concentration of trans-1,2-dichloroethene as low as 50 ppm. This finding cannot, however, be used as a biomarker of exposure because the amount of acetone exhaled was not correlated with different exposure concentrations. Furthermore, acetone exhalation is not specific for 1,2-dichloroethene since acetone can be found in blood and exhaled air after exposure to other chemicals such as vinyl chloride, vinylidene fluoride, and perchloroethylene (Filser and Bolt 1980), as well as in patients with diabetes, hepatic insufficiency, and other metabolic disorders. 2.6.2 Biomarkers Used to Characterize Effects Caused by 1,2-Dichloroethene There currently are no biomarkers available to characterize effects caused by 1,2-dichloroethene in humans. As discussed in Section 2.6.1, acetonemia and acetone exhalation were observed in rats after inhalation exposure to halogenated ethylenes, including the two isomers of 1,2-dichloroethene (Filser et al. 1978). Based on results of experiments with vinylidene fluoride, Filser and Bolt (1980) concluded that metabolites, rather than the parent compounds, were involved in invoking this response. Based on results of studies with the monohaloacetate metabolites of vinylidene fluoride and vinylidene chloride, which are known to inhibit enzymes of the citric acid cycle, Filser et al. (1982) suggested that the production of acetone by the halogenated ethylenes might also result from the inhibition of the enzymes of the citric acid cycle. This would lead to an increase in mitochondrial acetyl-coenzyme A and, consequently, to an alteration in lipid and fatty acid metabolism and ketosis. A similar mechanism was suggested for 1,2-dichloroethene because the primary metabolite, dichloroacetate, can also increase ketone levels in the body. If such a mechanism operated, acetone exhalation could conceivably serve as a biomarker for such effects as fatty degeneration of the liver, which has been 1,2-DICHLOROETHENE 58 2. HEALTH EFFECTS observed in rats exposed to 1,2-dichloroethene (Freundt et al. 1977). However, acetone exhalation is extremely common and is associated with some disorders that do not obviously produce any liver degeneration. For more information on biomarkers for renal and hepatic effects of chemicals see ATSDR/CDC Subcommittee Report on Biological Indicators of Organ Damage (1990) and for information on biomarkers for neurological effects see OTA (1990). 2.7 INTERACTIONS WITH OTHER CHEMICALS No studies were located regarding the health effects in humans or animals exposed to 1,2-dichloro- ethene in combination with other chemicals that are likely to be found with 1,2-dichloroethene in the environment, workplace, or at hazardous waste sites. As mentioned in Section 2.3.3, both isomers of 1,2-dichloroethene can inhibit the cytochrome P-450-dependent metabolism of hexobarbital (Freundt and Macholz 1978). Such inhibition has also been shown to increase hexobarbital sleeping time. Costa and Ivanetich (1982) showed that multiple forms of hepatic microsomal cytochrome P-450, including the forms induced by B-naphthoflavone and phenobarbital, can bind and metabolize 1,2-dichloroethene. Thus, 1,2-dichloroethene may potentiate the toxic actions of any chemical that undergoes detoxication by cytochrome P-450-dependent metabolism by competing for binding to the active site of cytochrome P-450. Conversely, 1,2-dichloroethene may antagonize the toxic actions of any chemical that undergoes toxic activation by cytochrome-P-450-dependent metabolism. 2.8 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE A susceptible population will exhibit a different or enhanced response to 1,2-dichloroethene than will most persons exposed to the same level of 1,2-dichloroethene in the environment. Reasons include genetic make-up, developmental stage, age, health and nutritional status (including dietary habits that may increase susceptibility, such as inconsistent diets or nutritional deficiencies), and substance exposure history (including smoking). These parameters result in decreased function of the detoxification and excretory processes (mainly hepatic, renal, and respiratory) or the pre-existing compromised function of target organs (including effects or clearance rates and any resulting 1,2-DICHLOROETHENE 59 2. HEALTH EFFECTS end-product metabolites). For these reasons we expect the elderly with declining organ function and the youngest of the population with immature and developing organs will generally be more vulnerable to toxic substances than healthy adults. Populations who are at greater risk due to their unusually high exposure are discussed in Section 5.6, Populations With Potentially High Exposure. While no populations with unusual susceptibility to the health effects of 1,2-dichloroethene could be identified, based on the available literature, certain diabetics may be unusually susceptible because of impairment of glucose metabolism and increased production of acetone. In addition, individuals with impaired livers, such as alcoholics, and those with exposure to other halogenated hydrocarbons may be unusually susceptible to 1,2-dichloroethene exposure. 2.9 METHODS FOR REDUCING TOXIC EFFECTS This section will describe clinical practice and research concerning methods for reducing toxic effects of exposure to 1,2-dichloroethene. However, because some of the treatments discussed may be experimental and unproven, this section should not be used as a guide for treatment of exposures to 1,2-dichloroethene. When specific exposures have occurred, poison control centers and medical toxicologists should be consulted for medical advice. 2.9.1 Reducing Peak Absorption Following Exposure 1,2-Dichloroethene is available commercially as the cis or trans isomer or as a mixture. Human exposure to 1,2-dichloroethene may occur by inhalation, ingestion, or by dermal contact. There are conflicting data regarding the relative toxicity of the two isomers. Vapors are extremely irritating to the eyes and upper respiratory tract, and once absorbed can cause central nervous system and respiratory depression. 1,2-Dichloroethene was used as a general anesthetic in humans, and central nervous system depression is one of its toxic effects (ACGIH 1991). It is recommended that exposed individuals be moved to fresh air and administered 100% humidified supplemental oxygen. The potential risk of aspiration, especially for infants, leading to airway and pulmonary damage, usually outweighs the potential benefit of administering syrup of ipecac to induce emesis (TOMES 1994). Once in the care of a health professional, gastric lavage can be useful if administered within 1 hour of the exposure to reduce the amount of absorbed solvent. 1,2-DICHLOROETHENE 60 2. HEALTH EFFECTS Following ocular contamination, the eyes should be irrigated with copious amounts of room temperature water or normal (0.9%, w/v, isotonic) saline, for at least 15 minutes. Reversible, corneal opacification has been described after exposure to 1,2-dichloroethene vapor, and ophthalmologic consultation should generally be sought after ocular contamination to evaluate the potential ocular damage (Gosselin 1984). Following acute exposure to many chlorinated solvents, hypotension and cardiac arrhythmias due to myocardial sensitization have led to ventricular fibrillation and death (TOMES 1994). Unfortunately there is no specific treatment for 1,2-dichloroethene exposure except for supportive measures to combat the effects of central nervous system, respiratory depression, and cardiac irritability. 2.9.2 Reducing Body Burden The body does not retain significant amounts of 1,2-dichloroethene. It is largely excreted through the lungs; thus, prompt and adequate ventilation is the only known way to reduce body burden (ACGIH 1991). There is no currently recognized treatment to enhance elimination, and orthodox treatment for ingestion is entirely supportive. 2.9.3 Interfering with the Mechanism of Action for Toxic Effects Clinical effects caused by acute exposure to 1,2-dichloroethene include central nervous system and respiratory depression, eye and upper respiratory irritation, nausea, vomiting, weakness, tremors, and epigastric cramps, all of which may resolve rapidly after the exposure ceases. There is one reported industrial fatality caused by inhalation of vapor in a small enclosure, but the level of exposure, symptoms of toxicity, and isomeric composition are unknown (ACGIH 1991). Muscular cramping and vomiting have been relieved by intravenous administration of calcium gluconate (Gosselin 1984). The mechanism of action for the central nervous system effects of 1,2-dichloroethene has not been clearly established, but may be related to solvent effects on cellular membranes. Neurotransmitter effects have also been demonstrated for some solvents, and it is reasonable to speculate that these effects on neurotransmitters might be mitigated by pharmacologic intervention. However, no such interventions are currently available for clinical use. Fatty degeneration of the liver has been reported in animal studies, but 1,2-dichloroethene appears to have less hepatic and renal toxicity than many other chlorinated hydrocarbons (ACGIH 1991). 1,2-DICHLOROETHENE 61 2. HEALTH EFFECTS However, ethanol in alcoholic beverages may compete with or enhance the metabolic activation of solvents and can increase the severity of health effects, particularly liver toxicity. Alcoholic beverages should be avoided following exposure to 1,2-dichloroethene and other solvents. 2.10 ADEQUACY OF THE DATABASE Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether adequate information on the health effects of 1,2-dichloroethene is available. Where adequate information is not available, ATSDR, in conjunction with the National Toxicology Program (NTP), is required to assure the initiation of a program of research designed to determine the health effects (and techniques for developing methods to determine such health effects) of 1,2-dichloroethene. The following categories of possible data needs have been identified by a joint team of scientists from ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would reduce the uncertainties of human health assessment. This definition should not be interpreted to mean that all data needs discussed in this section must be filled. In the future, the identified data needs will be evaluated and prioritized, and a substance-specific research agenda will be proposed. 2.10.1 Existing Information on Health Effects of 1,2-Dichloroethene The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 1,2-dichloroethene are summarized in Figures 2-4 and 2-5. The purpose of these figures is to illustrate the existing information concerning the health effects of 1,2-dichloroethene. Each dot in the figure indicates that one or more studies provide information associated with that particular effect. The dot does not necessarily imply anything about the quality of the study or studies, nor should missing information in this figure be interpreted as a "data need." A data need, as defined in ATSDR's Decision Guide for Identifying Substance-Specific Data Needs Related to Toxicological Profiles (ATSDR 1989), is substance-specific information necessary to conduct comprehensive public health assessments. Generally, ATSDR defines a data gap more broadly as any substance-specific information missing from the scientific literature. 1,2-DICHLOROETHENE 62 2. HEALTH EFFECTS Figure 2-4. Existing Information on Health Effects of cis-1,2-Dichloroethene “© & Systemic $° is > ® © 2 SE D> 0 XQ Q & Y/ SSL SSLS® e S/S / RF Oo & © S/S OF / «0 & & S° @ © & * RQ XP CL / & RUSSEL) REPS Inhalation Oral Dermal Human © & Systemic S° = > & S$ oN WE © S$ FS SS & EC / S/S SSS) NYA 74 S/S § e/ S/S LSS FS L ESL Inhalation ° Oral ® ® o ® ® J Dermal Animal ® Existing Studies 1,2-DICHLOROETHENE 63 2. HEALTH EFFECTS Figure 2-5. Existing Information on Health Effects of trans-1,2-Dichloroethene NY . @ Systemic © s N 2 Oo © @ OS “© &S eg / S/o SP S ES < 2 LSS SSL # ® / LL SL SES SRS SESS NSS) ELS SRS Inhalation ® Oral Dermal ® Human «OO ; x SZ Systemic oO KX Od > &¥ & o Sa & So S/S > Se SK \ S/S SoC a8 & XX QS S/S £ Q o o PSE SL SLSR SSE SS UNLESS Inhalation oo ° eo ® ® Oral ® ® @ & @ ® Dermal eo Animal ® Existing Studies 1,2-DICHLOROETHENE 64 2. HEALTH EFFECTS There are very few studies or case reports of human exposure to 1,2-dichloroethene by any route of exposure. One report describes neurologic symptoms in humans following acute inhalation of trans-1,2-dichloroethene. This property of depressing the central nervous system is an important effect of 1,2-dichloroethene exposure. Another study reported an industrial fatality related to accidental inhalation exposure to 1,2-dichloroethene (isomeric composition unknown). Information has been reported regarding the lethality and toxic effects of trans-1,2-dichloroethene in animals exposed by the inhalation and oral routes for acute and intermediate durations. For inhalation and oral exposure routes, toxicity to the heart, liver, blood, and lung has been reported. Central nervous system depression has been reported in animals given lethal doses of trans-1,2-dichloroethene by the oral route. Several studies examined the effects of either cis- or trans-1,2-dichloroethene on the immune systems of mice exposed by inhalation or oral routes. A 14-day and a 90-day gavage study of cis-1,2-dichloroethene found hematological effects in rats. No information is available on the toxic effects of chronic exposure to either cis- or trans-1,2-dichloroethene by any route. In addition to central nervous system effects, inhalation exposure to trans-1,2-dichloroethene appears to affect development of the fetus and development of the newborn and young. When inhaled, there also may be effects on reproduction because of reduced maternal weight gain and reduced litter size. As shown in Figures 2-4 and 2-5, no information on carcinogenic effects in animals by inhalation, oral, or dermal exposure is available for either cis- or trans-1,2-dichloroethene. No studies were located regarding genotoxic effects in humans or animals after inhalation, oral, or dermal exposure to 1,2-dichloroethene, but studies in mice injected intraperitoneally indicate that the cis isomer may be genotoxic; the trans isomer has shown no indication of being genotoxic. 2.10.2 Identification of Data Needs Acute-Duration Exposure. Reliable health effects data for human exposure by any route to 1,2-dichloroethene were not located. One human fatality was reported, but the cause of death, the length of exposure, and the concentration and isomeric identity of 1,2-dichloroethene in the air were not described (Hamilton 1934). Two human volunteers reported mild burning of the eyes after acute dermal exposure to trans-1,2-dichloroethene (Lehmann and Schmidt-Kehl 1936). However, the methods used in 1936 to generate and test for exposure levels were relatively insensitive, and it is unclear whether the 1,2-dichloroethene was in an aerosol or gaseous state. No information was located for systemic toxicity in humans after oral exposure or for the relative toxicities of the cis and trans 1,2-DICHLOROETHENE 65 2. HEALTH EFFECTS isomers of 1,2-dichloroethene in humans. The acute lethal levels of trans-1,2-dichloroethene were established after inhalation exposure in mice and after oral exposure in mice and rats (Barnes et al. 1985; Freundt et al. 1977; Gradiski et al. 1978; Hayes et al. 1987; Kallman et al. 1983; McMillan 1986; Munson et al. 1982). An acute-duration inhalation MRL was derived from the Freundt et al. (1977) study, based on the hepatic effect of fatty degeneration of the liver seen at 200 ppm in rats. A wide range of LDs, values for the trans isomer, 1,300-10,000 mg/kg/day, exists in the present literature. Inhalation LCs) and oral LDg, values for cis-1,2-dichloroethene are not well defined. One study suggests an LDs around 5,000 mg/kg/day for the cis isomer (McMillan 1986). Pathological lesions in the heart, liver, and lungs were reported in rats after acute inhalation exposure to trans-1,2-dichloroethene; however, the study was limited in size and scope (Freundt et al. 1977). Neurological problems, such as narcosis, lethargy, and behavioral changes, have been shown with acute inhalation of both cis and trans isomers (De Ceaurriz et al. 1983; Hurtt et al. 1993). Oral exposure to 1,2-dichloroethene is also associated with central nervous system depression and other neurological effects (Barnes et al. 1985; Hayes et al. 1987). The finding of acetone in the air exhaled by 1,2-dichloroethene-exposed rats indicates possible alterations in lipid and fatty acid metabolism at high exposure levels (Filser and Bolt 1980). This may support the observation of fatty infiltration of liver in the rat inhalation study. Evidence of target effects for oral acute exposure exists for both the cis and trans isomers. Hematotoxicity after acute oral exposure to cis- and trans-1,2-dichloroethene was reported in rats and mice and included adverse effects of decreases in fibrinogen levels, hematocrit, and erythrocyte counts (Barnes et al. 1985; McCauley et al. 1990). The NOAEL value for decreased hematocrit in female rats was used for the derivation of an acute oral MRL for cis-1,2-dichloroethene. Serious respiratory, cardiovascular, and hepatic effects were also noted in rats exposed orally. Along with the serious responses of pulmonary and fibrous hyperemia, alveolar distention, cardiac muscle changes, and decreases in blood urea nitrogen, milder hepatic changes were recorded (Barnes et al. 1985; Freundt et al. 1977; McCauley et al. 1990; McMillan 1986). Limited data were located for dermal exposure to trans-1,2-dichloroethene indicating mild to moderate, reversible, dermal and ocular effects (Brock 1990; Hurtt et al. 1993; Lehmann and Schmidt-Kehl 1936). The available toxicity data do not allow a definitive conclusion regarding the relative toxicity of the cis and trans isomers. However, in vivo and in vitro studies suggest differences in the metabolism of the two isomers (Filser et al. 1978, 1979, 1982; Gargas et al. 1988, 1989, 1990; Sato and Nakajima 1979). Furthermore, pharmacokinetic data are insufficient to identify target organs for either isomer across routes of exposure. Further studies to identify target organs of cis- and trans-1,2-dichloroethene toxicity and to assess dose-response relationships would be particularly useful 1,2-DICHLOROETHENE 66 2. HEALTH EFFECTS for inhalation and dermal exposure routes. Additional oral exposure studies would increase the possibilities of assessing dose-response relationships and target organs. The information is important for populations living near hazardous waste sites that might be exposed to 1,2-dichloroethene for brief periods of time. Intermediate-Duration Exposure. No studies were located regarding intermediate-duration exposure to 1,2-dichloroethene in humans by any route of exposure. Liver and lung toxicity of trans-1,2-dichloroethene in rats, similar to that found with acute exposure, was observed after intermediate-duration inhalation exposure (Freundt et al. 1977). The exposure level that was associated with capillary hyperemia, alveolar distention and pneumonic infiltration, and fatty accumulation in liver lobules and Kupffer cells was the same as that tested with acute exposure; therefore, an intermediate inhalation MRL at the same level as the acute inhalation MRL was derived. Studies in rats and mice exposed orally to trans-1,2-dichloroethene at doses ranging from 17 to 3,100 mg/kg/day (Barnes et al. 1985; Hayes et al. 1987; McCauley et al. 1990; McMillan 1986; Shopp et al. 1985) have examined many target organs including the blood, liver, kidneys, lungs, heart and immune system. Respiratory (lung weight), hematological (blood cell counts), and body weight effects were reported at doses of 100 to 400 mg/kg/day (Barnes et al. 1985; McCauley et al. 1990; McMillan 1986). Hepatic effects in male mice at 175 mg/kg/day and a NOAEL at 17 mg/kg/day are the basis for an intermediate-duration oral MRL for trans-1,2-dichloroethene (Barnes et al. 1985). Hematologic effects at 97 mg/kg/day and a NOAEL at 32 mg/kg/day are the basis of an intermediate-duration oral MRL for cis-1,2-dichloroethene. A 60-day oral study of trans-1,2-dichloroethene in rats, available as an abstract, indicated that the lungs, spleen, and kidney are targets (see Section 2.10.3). The full published report may provide dose-response data when it becomes available. The differences in the observed effects of cis- and trans-1,2-dichloroethene that were seen in rats in the oral 90-day studies may be due to differences in toxicity of these isomers as discussed above (see acute-duration exposure) (Barnes et al. 1985; Hayes et al. 1987; McCauley et al. 1990; McMillan 1986; Shopp et al. 1985). No studies were located regarding 1,2-dichloroethene toxicity in animals after dermal exposure. Additional studies regarding 1,2-dichloroethene toxicity after inhalation exposure are necessary, with a specific need for inhalation studies using the cis isomer. Because people living near hazardous waste sites may be exposed for longer periods of time, more dose-response data for intermediate-duration exposures by all routes are important. The target organs—Iliver, blood, and lungs—should be emphasized. 1,2-DICHLOROETHENE 67 2. HEALTH EFFECTS Chronic-Duration Exposure and Cancer. No human or animal data were located regarding health effects of long-term (chronic) exposure to 1,2-dichloroethene by inhalation, oral, or dermal routes. Therefore, no chronic MRLs could be derived. There is a need to conduct chronic animal studies with the isomers of 1,2-dichloroethene by inhalation, oral and dermal routes. These studies could provide information on subtle toxicological changes in organs/systems and on dose-response relationships associated with 1,2-dichloroethene toxicity. Furthermore, there are communities around hazardous sites that may be exposed to low levels of 1,2-dichloroethene for long periods of time. No studies were located regarding the carcinogenic potential of 1,2-dichloroethene in humans and animals following inhalation, oral, or dermal exposure. However, genotoxicity studies revealed mutagenic activity of the cis isomer in the host-mediated assay (Cantelli-Forti and Bronzetti 1988; Cerna and Kypenova 1977; Galli et al. 1982; Greim et al. 1975; Sawada et al. 1987). Furthermore, a 60-day oral study of trans-1,2-dichloroethene in rats, which was available in abstract form, indicated a high incidence of lymphosarcoma in the lungs (see Section 2.10.3). Although this study has not yet been published, it raises a concern about the carcinogenicity of 1,2-dichloroethene, which should be further investigated in long-term oral and inhalation studies of both isomers. In humans, dermal exposure is less likely than oral or inhalation exposure; however, dermal studies could add valuable insights about 1,2-dichloroethene toxicity. Genotoxicity. No study was located regarding 1,2-dichloroethene genotoxicity in humans. Neither isomer of 1,2-dichloroethene was mutagenic in in vitro experiments with E. coli, S. typhimurium, and S. cerevisiae (Cantelli-Forti and Bronzetti 1988; Cerna and Kypenova 1977; Galli et al. 1982; Greim et al. 1975). Neither isomer produced chromosomal aberrations or sister chromatid exchanges in Chinese hamster cells (Sawada et al. 1987). Reductions in numbers of convertants and revertants (positive results) were obtained with the cis isomer, but not the trans isomer, in host-mediated assays in mice (Cantelli-Forti and Bronzetti 1988). Furthermore, repeated intraperitoneal injections of the cis isomer induced chromosomal aberrations in mouse bone marrow cells (Cerna and Kypenova 1977); thus, cis-1,2-dichloroethene may be a potential mutagen in animals. The weight of evidence of genotoxicity is still small; additional studies would help to confirm the existing information or uncover unknown genetic effects. Chronic animal studies might elucidate the potential for, or isomeric differences in, cancer development. If an appropriate group of exposed workers could be identified, cytogenetic testing might help determine 1,2-dichloroethene's genotoxic potential in humans. 1,2-DICHLOROETHENE 68 2. HEALTH EFFECTS Reproductive Toxicity. No studies were located regarding reproductive toxicity of 1,2-dichloro- ethene in humans by inhalation, oral, or dermal exposure. No studies were located regarding reproductive toxicity of 1,2-dichloroethene in animals following dermal exposure. An inhalation study published in 1993 (Hurtt et al. 1993) is the sole report to address the reproductive effects of 1,2-dichloroethene. In this study, maternal weight gain was reduced, proportional to dose, and possible increases in resorption were reported. In other studies, histopathological examination of the reproductive organs of animals exposed orally for 90 days to 1,2-dichloroethene has not shown effects on reproductive organs (Hayes et al. 1987; McCauley et al. 1990). Further investigation of reproductive effects, including results of dermal exposure, are necessary for understanding possible effects suggested by the existing evidence on the reproductive system. Developmental Toxicity. No studies were located regarding developmental effects in humans after inhalation, oral, or dermal exposure to cis- or trans-1,2-dichloroethene. No data are available on developmental effects in animals after oral or dermal exposure to 1,2-dichloroethene. Fetal weights appear to be reduced after exposure to 1,2-dichloroethene, as shown in an inhalation study (Hurtt et al. 1993). During critical developmental stages (days 7-16 in rats), trans-1,2-dichloroethene exposure was associated with reduced weight gain in rat pups at a level of 12,000 ppm. Additional developmental toxicity studies in animals by inhalation, oral, and dermal exposure may provide relevant information for humans exposed near hazardous waste sites. Immunotoxicity. No information about 1,2-dichloroethene toxicity to the human immune system was located. Findings of fatty degeneration of Kupffer cells, decreased numbers of white blood cells, and pneumonic infiltration in rats after inhalation exposure to trans-1,2-dichloroethene (Freund et al. 1977), and of suppressed humoral immune status in male mice exposed to trans-1,2-dichloroethene in drinking water for 90 days, as measured by mouse spleen cell antibody production (Shopp et al. 1985), suggest that 1,2-dichloroethene may be immunotoxic. Immunological studies of cis-1,2-dichloroethene and additional studies of trans-1,2-dichloroethene would help determine more definitely the immunotoxic potential and possible differences between the isomers. No immunotoxicity data in animals were located for the dermal route of exposure. New dermal studies would be valuable, both because no such studies have been reported and because of the potential immuno-dermal effects of dermal exposure. 1,2-DICHLOROETHENE 69 2. HEALTH EFFECTS Neurotoxicity. Symptoms of central nervous system depression (vertigo, drowsiness, intracranial pressure, nausea) were observed in two human volunteers during a 30-minute inhalation exposure to 1,2-dichloroethene. The symptoms disappeared after discontinuation of exposure (Lehmann and Schmidt-Kehl 1936). No information was located regarding neurotoxicity after exposure by other routes of exposure in humans. In animals, inhalation exposure to 1,2-dichloroethene was associated with behavioral changes, narcosis, and lethargy at levels ranging from 1,700 to 12,000 ppm (De Caurriz et al. 1983; Hurtt et al. 1993). Similarly, symptoms of central nervous system depression were observed in rodents after acute oral exposure to 1,2-dichloroethene (Barnes et al. 1985; Hayes et al. 1987; McCauley et al. 1990; Munson et al. 1982). The observations were restricted to behavioral tests. Further information regarding 1,2-dichloroethene neurotoxicity in animals after exposure by inhalation, oral, and dermal routes would be valuable. Animal studies of the effects of 1,2-dichloro- ethene on the morphology of neurons, glial and myelinated cells, and on the synthesis and degradation of neurotransmitters would permit more accurate assessment of neurotoxic potential of this chemical. Epidemiological and Human Dosimetry Studies. No epidemiologic studies of populations exposed to 1,2-dichloroethene were located. The general population might be exposed to low levels of 1,2-dichloroethene in contaminated urban air or in contaminated drinking water, or possibly by dermal contact. The occupationally exposed population is relatively small (285 individuals) (NIOSH 1988). The confounding exposure to other related compounds makes it difficult to perform an epidemiological study for 1,2-dichloroethene. Animal studies suggest that hematological, hepatic, neurological and reproductive effects would be the end points of concern (Barnes et al. 1985; Freundt et al. 1977; Hurtt et al. 1993; McCauley et al. 1990; McMillan 1986). Therefore, if a worker or a population with appropriate exposure can be identified, epidemiological studies could be designed to study the possibility that similar effects may be observed in humans. Studies that correlate exposure with blood or urine levels of biomarkers and/or with effects would be useful in establishing causality. The knowledge of a dose-effect relationship would be useful for monitoring individuals near hazardous waste sites for preventive purposes. Biomarkers of Exposure and Effect. Exposure. Methods exist for determining 1,2-dichloroethene in blood and biological tissues (Ashley et al. 1992; Hara et al. 1980; Lin et al. 1982; Raymer et al. 1990; Streete et al. 1992; Uehori et al. 1987), but specific levels of 1,2-dichloroethene have not been correlated with exposure. Exhalation of 1,2-DICHLOROETHENE 70 2. HEALTH EFFECTS acetone and the presence of acetone in blood have been noted in rats after inhalation exposure to cis- and trans-1,2-dichloroethene, but the amounts exhaled or the levels in blood have not been correlated with exposure levels (Freundt et al. 1977). Furthermore, acetonemia is not specific for 1,2-dichloro- ethene; increased acetone levels were found after exposure to other chemicals (e.g., vinyl chloride and perchlorethylene) and in patients with diseases such as diabetes (Filser and Bolt 1980). Studies focusing on correlating blood or urine levels of 1,2-dichloroethene or its metabolites with exposure levels would be useful to facilitate future medical surveillance that can lead to early detection. Effect. No known biomarkers are currently used to characterize effects caused by 1,2-dichloroethene. Rats exposed by inhalation to halogenated ethylenes, including cis- and trans-1,2-dichloroethene, were shown to exhale acetone (Filser et al. 1978, 1980; Freundt et al. 1977). Based on these studies, a possible mechanism for the production of acetone was suggested, whereby a metabolite (dichloroacetate for 1,2-dichloroethene) inhibits the enzymes of the citric acid cycle, which would lead to an increase in mitochondrial acetyl-coenzyme A and, consequently, to an alteration in lipid and fatty acid metabolism to form ketone bodies (Filser et al. 1982). Further studies that support this hypothesis might determine whether acetone exhalation could serve as a biomarker for such effects as fatty degeneration of the liver, which was observed in rats exposed by inhalation to trans-1,2-dichloroethene (Freundt et al. 1977). Absorption, Distribution, Metabolism, and Excretion. The absorption, distribution, metabolism and excretion of a chemical can influence its toxicity. Several inhalation studies have examined the absorption of 1,2-dichloroethene, and they indicate that 1,2-dichloroethene vapors can be absorbed through the lung (Filser and Bolt 1979; Gargas et al. 1988, 1989; Lehmann and Schmidt- Kehl 1936). Studies by Gargas et al. (1988, 1989) and Sato and Nakajima (1979) determined 1,2-dichloroethene partition coefficients between a number of body tissues and show differences between the cis and trans isomers. The cis isomer has higher partition coefficients (tissue:air) and, therefore, greater affinity or absorption in biological tissue: These are important properties that influence toxicological effects. Absorption by the dermal route has not been investigated, although the lipophilic properties of this chemical make it likely. According to an ongoing study, trans-1,2-dichloroethene was quickly absorbed from the gastrointestinal tract of rats after oral exposure (see Section 2.10.3). No other studies on the absorption of 1,2-dichloroethene following oral exposure were located. The few oral toxicity studies support this conclusion (McCauley et al. 1990; McMillan 1,2-DICHLOROETHENE 71 2. HEALTH EFFECTS 1986). No studies were located regarding the distribution and excretion of 1,2-dichloroethene after inhalation, oral, or dermal exposure. Cytochrome P-450 has been implicated in the initial step of metabolism of 1,2-dichloroethene in the liver. Subsequent steps are believed to be catalyzed by cytosolic and/or mitochondrial aldehyde and alcohol dehydrogenases or related enzymes (Costa and Ivanetich 1982, 1984). Differences in the metabolism rate and the metabolite profile have been reported for the cis and trans isomers, for example, the cis isomer had a 4-fold greater turnover rate in hepatic microsomes in vitro than the trans isomer (Bonse et al. 1975; Costa and Ivanetich 1982, 1984). The metabolism of 1,2-dichloroethene has not been extensively studied in tissues other than the liver. Distribution studies of cis- and trans-1,2-dichloroethene and metabolites would help identify those tissues, if any, that accumulate them. Excretion studies of 1,2-dichloroethene and its breakdown products would be useful for understanding the metabolic fate of this chemical and determining major routes and rates of excretion. One important question to be addressed is the difference in metabolism and excretion at low and high exposure levels. Comparative Toxicokinetics. Although there are relatively few existing studies for comparative purposes, some general conclusions can be drawn. The human exposure studies consist of two inhalation studies from the 1930s, one of which is too sketchy to use in making any comparisons (Hamilton 1934; Lehmann and Schmidt-Kehl 1936). When two volunteers were exposed for 30 minutes to an unknown ratio of cis:trans 1,2-dichloroethene (Lehmann and Schmidt-Kehl 1936), their neurological responses were consistent with animal studies that show lethargy and drowsiness. No human toxicokinetic or dosimetry data were located. Among the animal species there is general consistency for both inhalation and oral exposure routes in the end points identified. Hepatic, hematological, and neurological end points are found in both rats and mice (Barnes et al. 1985; De Ceaurriz et al. 1983; McCauley et al. 1990; McMillan 1986). Investigation of 1,2-dichloroethene toxicokinetics in different animal species and comparison of detected metabolites with those detected in occupationally exposed individuals would be useful for determining an appropriate animal model for studying the toxicokinetics of 1,2-dichloroethene. Methods for Reducing Toxic Effects. General recommendations for reducing the absorption and metabolic responses to 1,2-dichloroethene are based on limited mitigation studies and reports found in the primary and review/consensus literature. Few individuals have received intense exposure 1,2-DICHLOROETHENE 72 2. HEALTH EFFECTS to 1,2-dichloroethene, whether accidental, clinical or occupational. Its neurological, hepatic, hematic, and respiratory effects are similar to those of other solvents, and therefore, generalized interventions have been drawn from experience with these other solvents. Supportive measures to combat the effects of central nervous system, respiratory depression, and cardiac irritability are the clinical recommendations (TOMES 1994). There is no specific treatment for 1,2-dichloroethene exposure, partly because its mechanisms of action are not well defined and the numbers of exposed individuals needing treatment are small. 2.10.3 Ongoing Studies Several abstracts of studies in progress were located. A high incidence of lymphosarcoma in the lungs and histopathological lesions in the spleen and kidneys was reported in rats after 60 days of oral treatment with 1/2, 1/20, and 1/200 of the reported LDgy, for trans-1,2-dichloroethene (Witmer et al. 1990). Absorption of trans-1,2-dichloroethene has been studied in rats after intravenous and oral applications (Manning et al. 1990). In these studies, trans-1,2-dichloroethene was quickly absorbed from the gastrointestinal tract reaching peak blood concentrations in 2-6 minutes after exposure. 1,2-DICHLOROETHENE 73 3. CHEMICAL AND PHYSICAL INFORMATION 3.1 CHEMICAL IDENTITY Information regarding the chemical identity of 1,2-dichloroethene is located in Table 3-1. 3.2 PHYSICAL AND CHEMICAL PROPERTIES Information regarding the physical and chemical properties of 1,2-dichloroethene is located in Table 3-2. There are two isomers of 1,2-dichloroethene, the cis form and the trans form. Some important characteristics of the two forms are that they possess a high vapor pressure and the vapor is heavier than air (HSDB 1995). The trans form is sufficiently volatile that 50% evaporates from water in 22 minutes when stirred at 25 °C; the cis form is similarly volatile (HSDB 1995). Experiments have shown that the degradation of the trans form is relatively slow due to ultraviolet irradiation, unless lamps of approximately 15-20 watts are used (Guertler et al. 1994) to allow greater relative stability of the vapor form in the environment. Table 3-1. Chemical Identity of 1,2-Dichloroethene Characteristic Information? mixture cis trans Chemical name Synonym(s) Registered trade name(s) Chemical formula Chemical structure Identification numbers: CAS registry NIOSH RTECS EPA hazardous waste OHM/TADS DOT/UN/NA/IMO shipping HSDB NCI 1,2,-Dichloroethene Acetylene dichloride;2'P 1,2-dichloroethene; 2: 1,2-dichloroethylene; sym-1,2-dichloroethylene 1,2-DCE Dioformd C,H,Cl,2® 540-59-02-¢ KV93600002:9 uo79* 8300194" UN 1150; dichloroethylene IMO 3.2; dichloroethylene 149 C560312:¢ cis-1,2-Dichloroethene (2)-1,2-dichloroethene;2:P (2)-1,2-dichloroethylene; 2° cis-acetylene dichloride; cis-1,2-dichloroethylene; cis-dichloroethylene Not available C,H,Cl,2¢ 156-59-22:¢ KV9420000%9 Not available 8300194" UN 1150; dichloroethylene IMO 8.2; dichloroethylene 5656 Not available trans-1,2-Dichloroethene (E)-1,2-dichloroethene;2P (E)-1,2-dichloroethylene; trans-acetylene dichloride; trans-1,2-dichloroethylene; trans-dichloroethylene Not available C,H,Cl,2€ Cl H 156-60-52:¢ KV94000002-9 uo79 8300194" UN 1150; 1,2-dichloroethylene IMO 3.2; 1,2-dichloroethylene 6361 Not available *This number, U079, applies to trans-1,2-dichloroethene and to the generic 1,2-dichloroethene (HSDB 1995). In effect, the hazardous waste number UO79 refers to a mixture containing tr. All information obtained from HSDB 1995, except where noted. PSANSS 1994 CChemline 1988 Bennett 1981 Environmental Protection Agency; HSDB = Hazardous Substances Data Bank; NCI = and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data €CAS 1994 Merck 1989 IRTECS 1994 POHM/TADS 1988 CAS = Chemical Abstracts Service; DOT/UN/NA/IMO = Dept. of Transportation/United Nations/ North America/International Maritime Dangerous Goods Code; EPA = ; 1,2-dichloroethene is a mixture containing trans-1,2-dichloroethene ans-1,2-dichloroethene. National Cancer Institute; NIOSH = National Institute for Occupational Safety System; RTECS = Registry of Toxic Effects of Chemical Substances NOILYWHOSNI TVOISAHd ANY TYOINIHD '€ INIHLIOHOTHOIQ-2't ve Table 3-2. Physical and Chemical Properties of cis- and trans-1,2-Dichloroethene Information Property cis trans Reference Molecular weight 96.95 96.95 Weast 1983; Merck 1989 Color Colorless Colorless Hawley 1981; HSDB 1995 Physical state Liquid Liquid Hawley 1981; HSDB 1995 Melting point -81.5°C -49.4 °C Weast 1983; Merck 1989 -80.5 °C -50.0 °C HSDB 1995 Boiling point 59.6 °C @ 745 mm Hg 47.2 °C 745 mm Hg Weast 1983; Merck 1989 Density at 20/4 °C Odor Odor threshold: Water Air Solubility: Water at 25 °C Organic solvents Partition coefficients: Log Kyw Log Kc Vapor pressure at 20 °C Vapor pressure at 30 °C 60.3 °C @ 760 mm Hg 1.2837 Ethereal, slightly acrid Sweet pleasant No data No data 3.5¢g/lL Soluble in ether, alcohol, benzene, acetone, chloroform 1.86 1.69 (estimated) 180 mm Hg 273 mm Hg; 250 mm Hg 48.0-48.5 °C @ 760 mm Hg 1.2565 Ethereal, slightly acrid Sweet pleasant 0.26 ppm 17 ppm v/v 0.084 ppm 6.3 g/L Soluble in ether, alcohol, benzene, acetone, chloroform 2.09 (recommended value) 2.06 1.56 (estimated) 265 mm Hg 395 mm Hg; 410 mm Hg Weast 1983; HSDB 1995 Merck 1989; HSDB 1995 HSDB 1995 HSDB 1995 Amoore and Hautala 1983 HSDB 1995 Horvath 1982; HSDB 1995 Weast 1983; HSDB 1995 Hansch and Leo 1985; HSDB 1995 HSDB 1995 Stevens 1979 HSDB 1995; Stevens 1979 NOILYWHOLNI TVOISAHd NV TvOIW3HO € 3INIHLIOHOTHOIa-2't SL TABLE 3-2. Physical and Chemical Properties of cis- and trans-1,2-Dichloroethene (continued) Information Property cis trans Reference Henry's law constant 4.08x10°3 9.38x103 Gossett 1987 at 24.8 °C atm-m3/mol atm-m%/mol 3.37x10°3 6.72x103 HSDB 1995 atm-m3/mol atm-m¥mol Autoignition temperature 460 °C 460 °C Sax 1979 Flashpoint 6 °C 2-4 °C Stevens 1979; HSDB 1995 Flammability limits in air 9.7-12.8 9.7-12.8 HSDB 1995 volume % volume % Conversion factors: ppm (V/V) to mg/m? 1 ppm i) = 1 ppm Vi) = in air at 25 °C 3.96 mg/m 3.96 mg/m 3 3_ 3 _ mg/m* to ppm (v/v) 1 mg/m” = 1 mg/m” = in air at 25 °C Explosive limits 0.25 ppm (V/V) 9.7-12.8% in air 0.25 ppm (v/v) 9.7-12.8% in air HSDB = Hazardous Substances Data Bank; v/v = volume per volume HSDB 1995; Stevens 1979 NOILVIWHO4NI TVOISAHd GNV TVOINIHO ‘€ 3IN3IHL3OHOTHOIg-2' + 9. 1,2-DICHLOROETHENE 77 4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 4.1 PRODUCTION 1,2-Dichloroethene has been produced as a commercial end product by the direct chlorination of acetylene at about 40 °C or by a technique involving the dehydrochlorination of 1,1,2-trichloroethane at 500 °C (HSDB 1995). Such commercial preparations are mixtures of cis- and trans-1,2-dichloro- ethene. The trans isomer is preferred in most industrial applications, which has tended to limit sales of the commercially available mixtures (HSDB 1995). 1,2-Dichloroethene is highly flammable and extremely corrosive, and yields the explosive compound chloroacetylene in the presence of copper or heated alkaline solutions (HSDB 1995). Industrial quantities of 1,2-dichloroethene are produced for on-site use in the production of other chlorinated compounds, which are the final commercial product. Columbia Organics of South Carolina, and Aldrich Chemical of Milwaukee, Wisconsin, sell research quantities of 1,2-dichloro- ethene (cis, trans, and mixture); Columbia Organics also sells cis-1,2-dichloroethene in 55-gallon drums (Kuney 1988; Van 1988). Complete data about the volume and trends of 1,2-dichloroethene production in the United States are not available (HSDB 1995). As with many chemicals, especially those whose production or use involves proprietary information, quantitative estimates of production are virtually impossible to obtain (Bason and Colborn 1992). Table 4-1 lists the facilities in each state that manufacture or process 1,2-dichloroethene, the intended use, and the range of maximum amount of 1,2-dichloroethene that is stored at the site. The data listed in Table 4-1 are derived from the Toxics Release Inventory (TRI93 1995). Only certain types of facilities were required to report and therefore this is not an exhaustive list. Twelve facilities were identified as producers or processors of 1,2-dichloroethene, with most of the producers located in Gulf Coast states (Louisiana and Texas). 4.2 IMPORT/EXPORT No data were found on U.S. imports or exports of 1,2-dichloroethene (HSDB 1995). Table 4-1. Facilities That Manufacture or Process 1,2-Dichloroethene Range of maximum amounts Facility Location ® on site in pounds Activities and uses VULCAN CHEMICALS WICHITA, KS 10,000-99,999 Produce; As a by-product; As a reactant WESTLAKE MONOMERS CORP. CALVERT CITY, KY 100,000-999,999 Produce; For on-site use/processing; As a reactant VULCAN MATERIALS CO. GEISMAR, LA 1,000-9,999 Produce; For on-site use/processing; As a by-product; As an impurity; As a reactant NA LA 100,000-999,999 Produce; As a by-product PPG IND. INC. LAKE CHARLES, LA 100,000-999,999 Produce; For sale/distribution; As a by-product; As an impurity NA LA 100,000-999,999 Produce; As a by-product DOW CHEMICAL CO. LA 10,000-99,999 Produce; As a by-product; As an impurity DOW CHEMICAL CO. FREEPORT, TX 100,000-999,999 Produce; For on-site use/processing; As a by-product; As an impurity; As a chemical processing aid UNION CARBIDE CORP. TEXAS CITY, TX No Data Produce; As a by-product OCCIDENTAL PETROLEUM CORP. TX 10,000-99,999 Produce; As a by-product GEON CO. LA PORTE, TX 1,000-9,999 Produce OCCIDENTAL PETROLEUM CORP. TX 10,000-99,999 Produce; As a by-product Source: TRI93 1995 a Post office state abbreviations used NA = not available IVYSOdSIA ANY ‘3SN ‘LHOdX3/1HOdWI ‘NOILONAOHd 3IN3IHL3OHOHOIa-2't 8L 1,2-DICHLOROETHENE 79 4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 4.3 USE 1,2-Dichloroethene is used primarily as a chemical intermediate in the synthesis of chlorinated solvents and compounds. It has also been used as a solvent for waxes, resins, acetylcellulose, perfumes, dyes, lacquers, thermoplastics, fats, and phenols. It is used in the extraction of rubber, as a refrigerant, in the manufacture of pharmaceuticals and artificial pearls, and in the extraction of oils and fats from fish and meat (HSDB 1995). It has also been used as a low-temperature extraction solvent for organic materials such as decaffeinated coffee (HSDB 1995). No information is available about how much, if any, 1,2-dichloroethene is currently used for solvent purposes. The trans isomer is more widely used in industry than either the cis isomer or the commercial mixture (Gosselin et al.1984). 4.4 DISPOSAL 1,2-Dichloroethene may be released from industries in waste water streams; however, these compounds can be removed from waste water by air stripping (Dilling 1977; Gossett 1987; Shen 1982a). Improved waste water treatment methods at publicly owned treatment works (POTWs) now use air stripping processes to remove most 1,2-dichloroethene and other volatile organic compounds (VOCs) from final effluents and deposit them in sludges or release them in air emissions (Bennett 1989). Product residues and sorbent media containing 1,2-dichloroethene may be packaged in epoxy-lined drums and disposed of at an EPA-approved landfill (OHM/TADS 1988). 1,2-Dichloroethene is a potential candidate for rotary kiln incineration at 820-1,600 °C with residence times of seconds for liquids and gases, and longer for solids; fluidized bed incineration at 450-980 °C with residence times of seconds for liquids and gases, and longer for solids; and liquid injection incineration at 650-1,600 °C with residence times of 0.1-2 seconds (HSDB 1995). Care must be exercised to assure complete combustion to prevent the formation of phosgene. Acid scrubbers are required to control air emissions. Information regarding the amount disposed of by each method is not available. Experiments using a vacuum-ultraviolet excimer flow-through reactor to degrade chloro-organic compounds in water have had promising results (Baum and Oppenldnder 1995). After 60 minutes of irradiation at 172 nm, the level of 1,2-dichloroethene in contaminated groundwater was reduced from 25 mg/L to below the detection limit of 0.1 mg/L. After 180 minutes of irradiation, more than 93% of the originally organic- bound chlorine atoms were converted to inorganic chloride ions. 1,2-DICHLOROETHENE 80 4. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL The EPA has identified trans-1,2-dichloroethene as a hazardous waste; its disposal is regulated under the Resource Conservation and Recovery Act (RCRA). Cis-1,2-dichloroethene has not been identified as a hazardous waste by the EPA. Specific information on federal regulations concerning hazardous waste disposal by land treatment, landfilling, incineration, thermal treatment, chemical/physical/biological treatment, underground injection and deep sea injection appears in the Code of Federal Regulations (40 CFR 190 to 399). Release of trans-1,2-dichloroethene in waste water is regulated under the Clean Water Act by the National Pollutant Discharge Elimination System (NPDES). Information regarding effluent guidelines and standards for trans-1,2-dichloroethene can be found in 40 CFR 122, 40 CFR 125, 40 CFR 413.02(i), 40 CFR 414, and 40 CFR 433.11(e). Pursuant to RCRA Section 3004(g)(5), EPA has restricted the land disposal of trans-1,2-dichloroethene (EPA 1988b). It may be disposed on land only if prior treatment standards have been met, or if disposal occurs in units that satisfy the statutory no-migration standard (EPA 1988b). Proper guidelines and standards are outlined in the Code of Federal Regulations (EPA 1988b). Current criteria for land treatment or burial are subject to significant revision; prior to implementing land disposal of waste residue (including waste sludge) environmental regulatory agencies should be consulted for guidance on acceptable disposal practices (HSDB 1995; OHM/TADS 1988). Rules and regulations regarding disposal practices are discussed in Chapter 7. 1,2-DICHLOROETHENE 81 5. POTENTIAL FOR HUMAN EXPOSURE 5.1 OVERVIEW 1,2-Dichloroethene is a compound produced by human industrial activities. Sources of environmental exposure to 1,2-dichloroethene include: process and fugitive emissions from its production and use as a chemical intermediate; evaporation from waste water streams, landfills, and solvents; emissions from combustion or heating of polyvinyl chloride and some vinyl copolymers; formation via anaerobic biodegradation of some chlorinated solvents; and leaching from landfills. Most of the 1,2-dichloro- ethene released in the environment will eventually enter the atmosphere or groundwater, where it may be subject to further biotic or abiotic degradation processes. 1,2-Dichloroethene is removed from the atmosphere chiefly through reaction with photochemically- generated oxygenated species (e.g., hydroxyl radicals). The estimated atmospheric lifetimes for cis- and trans-1,2-dichloroethene due to this removal process are 12 and 5 days, respectively (Goodman et al. 1986). Precipitation may also remove it; however, most 1,2-dichloroethene thus removed will probably reenter the atmosphere by volatilization. When released to surface water, volatilization is expected to be the primary fate process, with an estimated half-life of about 3—6 hours in a model river (Thomas 1982). When released to soil, 1,2-dichloroethene volatilizes rapidly from moist soil surfaces and leaches through subsurface soil, where it could become a groundwater contaminant. In groundwater, 1,2-dichloroethene is susceptible to anaerobic biodegradation. Experimental data indicate that the anaerobic biodegradation half-life of 1,2-dichloroethene is about 13-48 weeks (Barrio-Lage et al. 1986). Aerobic or facultative biodegradation processes have also been documented (Vannelli et al. 1990). Since 1,2-dichloroethene will often be found in mixtures with other chlorinated solvents, half-lives for degradation processes can be estimated only approximately. The general population may be exposed to low levels (0.013-0.076 ppb) of 1,2-dichloroethene through inhalation of contaminated air in urban areas (EPA 1983a). These exposure levels correspond to an average daily intake of 1-6 pg/day assuming an average daily intake of 20 m? of air. Additional exposure may occur from contaminated tap water, through consumption, inhalation during showering, and dermal contact. Occupational exposure may occur by inhalation and/or dermal contact. According to a 1981-1983 NIOSH survey, an estimated 215 workers in the United States are 1,2-DICHLOROETHENE 82 5. POTENTIAL FOR HUMAN EXPOSURE potentially exposed to 1,2-dichloroethene in the workplace (NIOSH 1988). This figure does not include firefighters and landfill workers. Cis-1,2-dichloroethene has been identified in at least 146 of the 1,430 current or former EPA National Priorities List (NPL) hazardous waste sites and trans-1,2-dichloroethene has been identified in at least 563 of the current or former NPL sites. In 336 of the NPL sites, 1,2-dichloroethene was identified but the isomer was not specified (HazDat 1996). However, the number of sites evaluated for 1,2-dichloro- ethene is not known. The frequency of these sites can be seen in Figures 5-1, 5-2, and 5-3, for cis, trans, and unspecified, respectively. Two of the sites where trans-1,2-dichloroethene was found are located in the Commonwealth of Puerto Rico (not shown) and all other sites are located in the United States. 5.2 RELEASES TO THE ENVIRONMENT 5.2.1 Air 1,2-Dichloroethene may be released to the atmosphere in emissions from production facilities, contaminated waste waters, contaminated waste disposal sites, and the pyrolysis and combustion of polyvinyl chloride and some vinyl copolymers. It may also be released during its use as a solvent and extractant, in organic synthesis, and in the manufacture of perfumes, lacquers, and thermoplastics. (HSDB 1995; Michal 1976; Shen 1982b). Not enough data are currently available to estimate the total amount of 1,2-dichloroethene released to the atmosphere. According to the Toxics Release Inventory (TRI), an estimated total of 29,478 pounds of 1,2-dichloro- ethene representing >99.9% of the total environmental release was discharged to air from manufacturing and processing facilities in the United States in 1993 (TRI93 1995). Table 5-1 lists the amounts released from each of these identified facilities. The TRI data should be used with caution since only certain types of facilities are required to report. Therefore, this is not an exhaustive list. There is a potential for atmospheric release of 1,2-dichloroethene from hazardous waste sites. Cis-1,2-dichloroethene has been detected in air samples from 3 of the 146 NPL sites where cis-1,2-dichloroethene has been identified in some medium (HazDat 1996). Trans-1,2-dichloroethene Figure 5-1. Frequency of Sites with cis-1,2-Dichloroethene Contamination EZ 6 - 10 EE 11-15 +0 | 16 - 20 Derived from HazDat 1996 3FHNSOdX3 NYIWNH HOH TVILN31O0d 'S 3N3HLIOHOTHOIa-2 + £8 Figure 5-2. Frequency of Sites with trans-1,2-Dichloroethene Contamination 3NIHL30HOTHOIa-C'} cee) YR ad xe lili Yes iE Ma jadwlsl 2f-orlelee tated Th trate Loeneriiiiliiggileliiilille ll EX rd Redan dl EE bacgiitiadticislel tel ini 3 SAT hateful Te eller ee FTE] Rann) aidsdadad] 00 ITT cee a TT — fire le let et KALL BPRSSe ananenany 0 Jor omg nll ep Tee Ll LL IN pede aay . eleletetete renee vel ill IRESIA fanaa Larne, es st LT tes tat taal le ore MHL HE EGO HEH TH Dada, JiaEa ies teil als Je sat eal ta tae atte ta ta BR ta tt a Taal OE phen "en Ys ay JalErelars sma mie ay ele Tm tara WBgRR SR + [ev se tela Jew erate cadet etal Te tele ees SITES NA OCCIDENTAL PETROLEUM CORP. TX NA OCCIDENTAL 190 190 PETROLEUM CORP. TX TEXAS CITY UNION CARBIDE CORP. 1,613 1,613 Totals 29,478 28 29,506 2,623 Source: TRI93 1995 2 post office state abbreviations used The sum of all releases of the chemical to air, land, water, and underground injection wells by a given facility NA = not available; POTW = publicly owned treatment works 34NSOdX3 NVWNH HOH TVILN3ILOd 'S 3IN3IHLIOHOHOIa-2't 98 1,2-DICHLOROETHENE 87 5. POTENTIAL FOR HUMAN EXPOSURE has been detected in air samples from 17 of the 563 NPL sites where trans-1,2-dichloroethene has been identified in some medium (HazDat 1996). 1,2-Dichloroethene (isomer unspecified) has been detected in air samples from 15 of the 336 NPL sites where 1,2-dichloroethene has been identified, without specifying the isomer, in some medium (HazDat 1996). While there is disagreement in the literature on the persistence of 1,2-dichloroethene released to the atmosphere, the half-lives would likely be measured in days, allowing for transport over large regional or even continental areas (Hall et al. 1989; Winer and Atkinson 1987). However, areas like southern California, where 1,2-dichloroethene is not commonly used as an end product or a chemical intermediate, have not shown detectable levels of 1,2-dichloroethene in ambient air. 5.2.2 Water 1,2-Dichloroethene may be released to surface waters via surface runoff from contaminated waste disposal sites, waste water from a variety of industrial sources, and from some publicly owned treatment works (POTWs). 1,2-Dichloroethene may be found in effluents from manufacturing and processing sites and from industries involved in its use as a solvent and extractant, in its use in organic synthesis, and in its use in the manufacture of perfumes, lacquers, and thermoplastics (Hawley 1981). As part of a comprehensive EPA survey of industrial facilities and POTWs, 4,000 samples of waste water were analyzed. The findings indicate that cis- or trans-1,2-dichloroethene is sometimes found in waste water from: petroleum refining; coal mining; foundries; nonferrous metal manufacture; POTWs; paint and ink formulation; rubber processing; steam electricity generation; leather tanning; iron and steel manufacture; textile mills; auto and other laundries; explosives factories; and production of inorganic chemicals, mechanical products, plastics and synthetics, electrical components and electronics, pharmaceuticals, organic chemicals and plastics, and transportation equipment (EPA 1980b; Shackelford et al. 1983). Effluents from iron, steel, and nonferrous metal manufacturing; and organics, plastics, and rubber processing exceeded 100 ppb of cis-1,2-dichloroethene. Effluents of iron and steel manufacturing, electronics, and POTWs also contained trans-1,2-dichloroethene (see Section 5.4.2) (Shackelford et al. 1983). It has been estimated that between 1982 and 1984, trans-1,2-dichloro- ethene was loaded into the Niagara River at an average of 13.6 pounds per day (Spagnoli 1986). Insufficient data are available to estimate the amount of 1,2-dichloroethene released to other surface waters in the United States. 1,2-DICHLOROETHENE 88 5. POTENTIAL FOR HUMAN EXPOSURE During the 1980s, as steady progress was made in negotiating final discharge permits for POTWs under EPA's National Pollutant Discharge Elimination System (NPDES) permitting program, the incidence of 1,2-dichloroethene inputs to surface waters from point source discharges may have substantially decreased. Improved levels of waste treatment have the potential to remove virtually all VOCs from final effluents. These materials will become air emissions or become immobilized in sludges (Bennett 1989). According to TRI93 (TRI93 1995), an estimated total of only 28 pounds of 1,2-dichloroethene, representing <0.1% of the total environmental release, was discharged to water from manufacturing and processing facilities in the United States in 1993. Table 5-1 lists the amounts released to water from each of the identified facilities. The TRI data should be used with caution since only certain types of facilities are required to report; therefore, this is not an exhaustive list. 1,2-Dichloroethene may be released to groundwater as a result of leaching from contaminated waste disposal sites, and by anaerobic degradation of other more highly chlorinated ethenes and ethanes present in groundwater (Cline and Viste 1985; HSDB 1995; Parsons et al. 1984; Smith and Dragun 1984). Barber et al. (1988) reported 280 ppb of 1,2-dichloroethene (isomer unspecified) in groundwater under a sandy rapid infiltration site that had received secondary sewage effluent since 1936. 1,2-Dichloroethene in drinking water may result from raw water source contamination (Otson et al. 1982). There is very little documentation of direct 1,2-dichloroethene contamination of groundwater. Research suggests that most 1,2-dichloroethene detections in groundwater involve biodegradation processes related to primary pollution from trichloroethylene (TCE) or tetrachloroethylene (PCE) (see Section 5.3). In addition to spills or leachates from waste disposal sites, groundwater may be contaminated by cracked sewer interceptors carrying industrial wastes. Especially after rains, substantial loadings may leave the interceptor system through infiltration and inflow (I&I) processes and enter groundwater supplies. Such phenomena have been documented in Europe (Milde et al. 1988) and similar 1&I problems are common in most older U.S. cities. 1,2-DICHLOROETHENE 89 5. POTENTIAL FOR HUMAN EXPOSURE There is also a potential for release of 1,2-dichloroethene to water from hazardous waste sites. Cis-1,2-dichloroethene has been detected in groundwater samples collected at 130 of the 146 NPL sites, in surface water samples collected at 14 of the 146 NPL sites, and in leachate samples collected at 8 of the 146 NPL sites where cis-1,2-dichloroethene has been identified in some medium (HazDat 1996). Trans-1,2-dichloroethene has been detected in groundwater samples collected at 487 of the 563 NPL sites, in surface water samples collected at 137 of the 563 NPL sites, and in leachate samples collected at 48 of the 563 NPL sites where trans-1,2-dichloroethene has been identified in some medium (HazDat 1996). 1,2-Dichloroethene (isomer unspecified) has been detected in groundwater samples collected at 263 of the 336 NPL sites, in surface water samples collected at 57 of the 336 NPL sites, and in leachate samples collected at 29 of the 336 NPL sites where 1,2-dichloroethene (isomer unspecified) has been identified in some medium (HazDat 1996). ~ 5.2.3 Soil Cis- and trans-1,2-dichloroethene are released to soil from the disposal of waste materials containing these compounds (Barber et al. 1988; Fain et al. 1987). They also may be formed in landfills, aquifers, or sediments as anaerobic biodegradation products of tetrachloroethene, trichloroethene, 1,1,1-trichloroethane, and 1,1,2,2-tetrachloroethane, solvents commonly found in municipal and industrial landfills (Parsons et al. 1984; Smith and Dragun 1984). In muck and sediment microcosms, tetrachloroethylene is converted to 1,2-dichloroethene with a preponderance of the cis isomer (Parsons et al. 1984). Cis-1,2-dichloroethene apparently is the more common isomer found, although it may be mistakenly reported as the trans isomer. Because it is a priority pollutant, the trans isomer is more commonly analyzed for, and the analytical procedures used generally do not distinguish between isomers (Cline and Viste 1995). Insufficient data are available to estimate the amount of 1,2-dichloro- ethene released to soil. According to TRI93 (TRI93 1995), no 1,2-dichloroethene was released to land from manufacturing and processing facilities in the United States in 1993. Table 5-1 lists the amounts released from these facilities. The TRI data should be used with caution since only certain types of facilities are required to report; therefore, this is not a comprehensive list. Available information for aquatic sediments is also very limited. Some researchers feel that the subsurface behavior of 1,2-dichloroethene would be similar in groundwater, soils, and sediments (Yeh 1,2-DICHLOROETHENE 90 5. POTENTIAL FOR HUMAN EXPOSURE and Kastenberg 1991). Most empirical information, however, derives from groundwater remediation studies, usually involving controlled laboratory microcosm studies. For some highly polluted waterbodies, for instance the Delaware and Raritan Canal, 1,2-dichloroethene detections in the water column probably reflect extensive contamination with chlorinated toxics in the sediments (Granstrom et al. 1984). Analyzing cause-source pathways in such complicated systems can be extremely difficult. There is also a potential for release of 1,2-dichloroethene to soils and sediments from hazardous waste sites. Cis-1,2-dichloroethene has been detected in soil samples collected at 12 of the 146 NPL sites, in sediment samples collected at 1 of the 146 NPL sites where cis-1,2-dichloroethene has been identified in some medium (HazDat 1996). Trans-1,2-dichloroethene has been detected in soil samples collected at 179 of the 563 NPL sites, in sediment samples collected at 61 of the 563 NPL sites, in sludge samples collected at 14 of the 563 NPL sites where trans-1,2-dichloroethene has been identified in some medium (HazDat 1996). 1,2-Dichloroethene (isomer unspecified) has been detected in soil samples collected at 76 of the 336 NPL sites, in sediment samples collected at 30 of the 336 NPL sites where 1,2-dichloroethene (isomer unspecified) has been identified in some medium (HazDat 1996). 5.3 ENVIRONMENTAL FATE 5.3.1 Transport and Partitioning Occurrence of 1,2-dichloroethene in rainwater samples (Kawamura and Kaplan 1983) indicates that this compound may be removed from the atmosphere by precipitation; however, most of the 1,2-dichloroethene so removed is likely to reenter the atmosphere by volatilization. Organics with a vapor pressure of >107 mmHg should exist almost entirely in the vapor phase in the atmosphere (Eisenreich et al. 1981). Thus, cis- and trans-1,2-dichloroethene, which have vapor pressures of 215 and 336 mmHg at 25 °C, respectively (Stevens 1979), are not expected to partition from the vapor phase to particulates in the atmosphere. Because it is relatively long-lived in the atmosphere, significant transport from source areas should occur (HSDB 1995). The dominant removal mechanism for 1,2-dichloroethene in surface waters is volatilization (EPA 1979). Henry's Law constants are 4.08x10"3 atm-m3/mol at 24.8 °C for cis-1,2-dichloroethene and 9.38x1072 atm-m3/mol at 24.8 °C for trans-1,2-dichloroethene (Gossett 1987). Based on these values, the volatilization half-life from a model river 1 m deep, flowing 1 m/second with a wind speed of 1,2-DICHLOROETHENE 91 5. POTENTIAL FOR HUMAN EXPOSURE 3 m/second is estimated to be 3 hours, using the method of Thomas (1982). Dilling (1977) experimentally determined that the volatilization half-life in an open beaker containing 1 ppm of test compound at a solution depth of 6.5 cm under continuous stirring (200 rpm) was 19 minutes for the cis isomer and 24 minutes for the trans isomer. These values correspond to volatilization half-lives of 5.0 and 6.2 hours, respectively, from a body of water 1 m deep. In fish, bioconcentration factors (BCFs) ranging between 5 and 23 have been estimated for the 1,2-dichloroethene isomers using linear regression equations based on log K and water solubility data (Bysshe 1982; Hansch and Leo 1985; Horvath 1982; Lyman et al. 1982). A BCF value of 6 for the fathead minnow (Pimephales promelas) was estimated in ASTER (1994) using the method of Veith and Kosian (1983). These estimated BCFs suggest that 1,2-dichloroethene does not bioconcentrate significantly in aquatic organisms. Based on this information, there is little potential for biomagnification within aquatic food chains. Soil adsorption coefficients (K.) of 32-49 were estimated for the 1,2-dichloroethene isomers using a linear regression equation based on water solubility data (Lyman 1982) and the structure-activity relationship developed by Sabljic (1984). These K . values suggest that adsorption of the 1,2-dichloroethene isomers to soil, sediment, and suspended solids in water is not a significant fate process. Without significant adsorption to soil, 1,2-dichloroethene can leach into groundwater where very slow biodegradation should occur (HSDB 1995). The presence of 1,2-dichloroethene in groundwater, especially under sandy soil (Barber et al. 1988), substantiates its leachability. The relatively low K . and high vapor pressure of 1,2-dichloroethene indicate that this compound should also readily volatilize from moist soil surfaces (Swann et al. 1983). 5.3.2 Transformation and Degradation 5.3.2.1 Air The dominant atmospheric removal process for 1,2-dichloroethene is predicted to be reaction with photochemically generated oxygenated species (e.g., hydroxyl radicals) in the troposphere. The estimated atmospheric lifetimes for cis- and trans-1,2-dichloroethene due to this removal process are 12 and 5 days, respectively (Goodman et al. 1986). These estimates are based on experimentally 0-12 determined hydroxyl reaction rate constants of 2.0x1 cm3/molecules-sec at 25 °C for the cis 1,2-DICHLOROETHENE 92 5. POTENTIAL FOR HUMAN EXPOSURE isomer and 4.5x10"12 cm3/molecules-sec at 25 °C for the trans isomer. Formyl chloride has been positively identified as a product of this reaction. Experimental data indicate that the reaction of cis- and trans-1,2-dichloroethene with ozone, nitrate radicals, or singlet oxygen in the troposphere is too slow to be environmentally significant (Atkinson and Carter 1984; Sanhueza and Heicklen 1975a, 1975b). The half-life resulting from ozone attack of the double bond is 44 days for the trans isomer and 129 days for the cis isomer (Tuazon et al. 1984). There also is evidence that cis-1,2-dichloro- ethene will be scavenged by rain (HSDB 1995) The primary ultraviolet (UV) absorption band for cis-1,2-dichloroethene is at 190 nm, which extends to about 240 nm (Ausbel and Wijnen 1975). The primary UV absorption band for the trans isomer also extends to about 240 nm (Dahlberg 1969). A minute amount of light is absorbed in the environmentally significant range (wavelengths greater than 290-380 nm). However, such absorption is insufficient for direct photolysis to be a significant fate process in the atmosphere. Giirtler et al. (1994) investigated the photochemical decomposition and oxidation of the chloroethenes in the gas phase by irradiation with a low-pressure mercury lamp in an oxygen atmosphere. Trans-1,2-dichloroethene slowly disappears after several hours of irradiation at 254 nm. After a period of restrained degradation, sudden decomposition is observed, probably resulting from the start of a chain mechanism. Trans-1,2-dichloroethene decomposes more slowly at low concentrations than at high ones. The primary photooxidation products are formyl chloride and, in small amounts, monochloro-acetyl chloride and dichloroacetaldehyde. Further photooxidation leads to the formation of phosgene, additional formyl chloride, formaldehyde, carbon monoxide, carbon dioxide, and hydrochloric acid. In polluted urban airsheds, photolytic processes are a major factor in generating free radicals. Several studies summarized in Hall et al. (1989) emphasize that 1,2-dichloroethene degradation will proceed 2—4 times faster in polluted urban air exposed to UV radiation than with "pure air" contained no free radical precursors. Tuazon et al. (1988) and Jeffers et al. (1989) provide other convenient summaries of the reaction chemistry of chloroethenes and OH radicals. 1,2-DICHLOROETHENE 93 5. POTENTIAL FOR HUMAN EXPOSURE 5.3.2.2 Water There is relatively little literature dealing with 1,2-dichloroethene fate and transport in surface waters. Since 1,2-dichloroethene is appreciably volatile, the usual assumption is that 1,2-dichloroethene introduced into surface waters will rapidly be transferred to the atmosphere (see Section 5.3.1). Chemical hydrolysis and oxidation are probably not environmentally important fate processes for 1,2-dichloroethene (EPA 1979, 1981a, 1984). Kinetic data pertaining specifically to the abiotic degradation of the 1,2-dichloroethene isomers in the environment were not located. Direct photolysis of 1,2-dichloroethene is also not likely to be important in sunlit natural waters (EPA 1979) (see Section 5.3.2.1). When dealing with surface waters, 1,2-dichloroethene and other chlorinated ethenes generally resist biodegradation under aerobic conditions (Fogel et al. 1986; Mudder 1981; Mudder and Musterman 1982). However, in one study, the 1,2-dichloroethene isomers were susceptible to aerobic biodegradation. In this study (Tabak et al. 1981), settled domestic waste water was used as the inoculum with 5 ppm each of the cis and trans isomers. Losses in 7 days were 54% of the cis isomer and 67% of the trans isomer. Losses due to volatilization over a 10-day period were 34 and 33% for the cis and trans isomers, respectively. The inoculum may have contained a facultative methanotroph capable of degrading the dichloroethenes (Fogel et al. 1986). No information was found regarding biodegradation in biological waste treatment plants. There is a growing body of literature dealing with fate and transport processes in groundwater. These studies are related to programs under the EPA Safe Drinking Water Act that address health risks from VOC contaminants in community drinking water systems, and to efforts to mitigate pollution at older waste disposal sites and remediate areas showing smaller-scale spills. While work through the early 1980s focussed on the biodegradation of 1,2-dichloroethene itself, it quickly became apparent that 1,2-dichloroethene contamination at many sites was part of a complicated series of biotransformations where such solvents as trichloroethylene or tetrachloroethylene were the principle driving forces (Vogel et al. 1987). 1,2-Dichloroethene undergoes slow reductive dechlorination under anaerobic conditions (Barrio-Lage et al. 1986; Fogel et al. 1986). In one study, anoxic microcosms containing uncontaminated organic sediment and water to simulate the groundwater environment were spiked with 5S mg/L of test 1,2-DICHLOROETHENE 94 5. POTENTIAL FOR HUMAN EXPOSURE compound. First-order rate constants were obtained that correspond to half-lives of 88-339 and 132-147 days for the cis and trans isomers, respectively. No degradation occurred in sterile microcosms; thus, loss of the compounds was assumed to be due entirely to anaerobic biodegradation. The cis isomer degraded to chloroethane and vinyl chloride (a human carcinogen), while the trans isomer degraded to vinyl chloride only (Barrio-Lage et al. 1986). When cis- and trans-1,2-dichloro- ethene were incubated with methanogenic aquifer material from a site near a landfill, at least 16 weeks passed before trans isomer degradation began (Wilson et al. 1986). During the same time, the cis isomer was reduced to <2% of the concentration in the autoclaved control, and vinyl chloride appeared after only 1-2 weeks incubation; therefore, the cis isomer degrades more rapidly. After 40 weeks, the trans isomer concentration fell to 18% of that in the autoclaved control containing the trans isomer. Trace amounts of the cis isomer remained in the unsterilized microcosm beyond 40 weeks. Tandoi et al. (1994) found that an anaerobic enrichment culture, using methanol as an electron donor, rapidly metabolized cis-1,2-dichloroethene to vinyl chloride with near zero-order kinetics and apparent inhibition of subsequent vinyl chloride dechlorination. Trans-1,2-dichloroethene was converted to vinyl chloride more slowly with first order kinetics and an estimated half-life of 9.5 hours and did not inhibit vinyl chloride dechlorination. Hopkins and McCarty (1995) performed an evaluation of the aerobic cometabolism of dichloroethene isomers, using phenol and toluene as the primary substrates, in a shallow aquifer at a pilot test facility. In an earlier study, a methane substrate was highly successful at transforming trans-1,2-dichloroethene in groundwater, but removal efficiency was rather low for cis-1,2-dichloroethene. Phenol was found to be superior to methane for in situ degradation of cis-1,2-dichloroethene, providing up to 90% removal in one pass at concentrations up to 1 mg/L. Removal of trans-1,2-dichloroethene was 74% when phenol was used. Semprini (1995) also demonstrated in pilot scale field studies of aerobic cometabolic transformations that indigenous microbes grown on phenol are more effective at degrading cis-1,2-dichloroethene than are microbes grown on methane. A study was performed on a sand aquifer at an industrial site near the town of St. Joseph, Michigan, to improve the understanding of the distribution of chlorinated aliphatic hydrocarbons (CAHs) years after contamination occurred (Semprini 1995). Groundwater concentrations varied significantly with depth. Relatively high concentrations of CAHs existed at all locations within 20 m of the center of the plume. The dominant dichloroethene isomer present was the cis isomer, with maximum 1,2-DICHLOROETHENE 95 5. POTENTIAL FOR HUMAN EXPOSURE concentrations of the cis and trans isomers of 133 and 3.9 mg/L, respectively. Cis-1,2-dichloroethene was observed in a transition zone between high and decreasing trichloroethene concentrations. Anaerobic biotransformation by methanogenic bacteria was the earliest documented research on the biodegradation of 1,2-dichloroethene. In addition to studies in the United States (Barrio-Lage at al. 1986; Ehlke et al. 1992; Parsons et al. 1984; Silka and Wallen 1988), there has been good documentation of similar phenomena in sandy aquifers near Berlin, Germany (Kastner 1991; Leschber et al. 1990) and in groundwater supplies near a landfill in Ottawa, Canada (Lesage et al. 1990). In addition to anaerobic pathways, laboratory studies suggest that ammonia-oxidizing aerobic bacteria (Vannelli et al. 1990) and facultative sulfur-bacteria (Bagley and Gossett 1990) can biodegrade chlorinated aliphatic hydrocarbons. Burback and Perry (1993) demonstrated that 1,2-dichloroethene, when added singly to groundwater, is catabolized by Mycobacterium vaccae. At 100 ppm, 1,2-dichloroethene was catabolized <50%. A wide range of estimates for reaction rates and pollutant half-lives have been reported. The biodegradation processes appear to be highly site specific, and influenced by the types of bacteria present, the presence of aerobic or anaerobic conditions, the presence of other substrates such as methane or sulfide, and the toxicity impacts from the various metabolites (Janssen et al. 1988). 5.3.2.3 Sediment and Soil Studies showing that cis- and trans-1,2-dichloroethene degrade in nonsterile groundwater microcosms (Barrio-Lage et al. 1986; Wilson et al. 1986) suggest that these compounds undergo anaerobic biodegradation in soil and that this process may be the sole mechanism by which 1,2-dichloroethene degrades in soil. Hallen et al. (1986) found that when cis- and trans-1,2-dichloroethene were incubated in a system inoculated with anaerobic sludge from a municipal digester to simulate anaerobic conditions in a landfill, vinyl chloride appeared within 6 weeks. Biodegradation of trans-1,2-dichloroethene was studied in microcosms containing uncontaminated organic sediment from the Everglades and allowed to stand to ensure oxygen depletion. Under these anoxic conditions, 50% of the chemical was lost within 6 months (Barrio-Lage et al. 1986). The fact that ethyl chloride as well as vinyl chloride are produced indicates that there are different pathways in the sequential dechlorination of cis-1,2-dichloroethene. 1,2-DICHLOROETHENE 96 5. POTENTIAL FOR HUMAN EXPOSURE There are no transformation and degradation studies dealing with sediments. 1,2-Dichloroethene does not show significant bioconcentration or bioaccumulation tendencies, and outside groundwater would tend to volatilize and move to the atmosphere. Some researchers feel that the behavior of 1,2-dichloroethene in sediments would be similar to patterns documented for soils or groundwater (Yeh and Kastenberg 1991). 5.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 5.4.1 Air 1,2-Dichloroethene has been frequently detected in air samples from urban locations throughout the United States and in landfill gas. Data in Table 5-2 represent available air monitoring data for 1,2-dichloroethene. Only one rural air monitoring study was located (Grimsrud and Rasmussen 1975). Maximum 1,2-dichloroethene concentrations detected in landfill gas ranged from 3,260 ppb (Vogt and Walsh 1985) in a municipal landfill simulator to 75,600 ppb at two Long Island landfills (Lipsky and Jacot 1985). In 1986, EPA carried out an update to its National Ambient Database, with a focus on updating the coverage for VOCs (Shah and Singh 1988). Based on information from 161 data points, outdoor 1,2-dichloroethene daily ambient air concentrations averaged 0.326 ppb, with a median of 0.037 ppb and with 75% of the values falling below a concentration of 0.113 ppb. With steady improvements in the efficiency of waste water treatment plants, the loadings of various toxics to receiving waters has substantially decreased over the last decade (Bennett 1989). However, reductions to surface water loadings have often resulted in increased emission to the atmosphere as volatile constituents of the waste influents are removed through techniques such as air stripping. Wastes, including organics like 1,2-dichloroethene, will also be transferred to sludges generated from biotic digestion processes or the use of chemical coagulants. Where sludge drying beds are located close to waste water plants, volatile constituents in the residuals will be vented to the air. These phenomena can present toxic exposure risks to workers at the treatment plants and to populations living close to these facilities. Table 5-2. Air Monitoring Data for 1,2-Dichloroethene Concentration Media Location Sampiing date isomer (ppb)? Comments Reference Ambient air Houston, TX cis 0.071 (mean) General urban EPA 1983a St. Louis, MO May 1980 0.039 (mean) atmosphere Denver, CO May-June 1980 0.076 (mean) Riverside, CA June 1980 0.060 (mean) Staten Island, NY July 1980 0.018 (mean) Pittsburgh, PA March-April 1981 0.013 (mean) Chicago, IL April-May 1981 0.019 (mean) Edison, NJ NS NS 1.3 (max.) Kin-Buc disposal site Pellizzari 1978 Tulsa, OK NS NS <0.1 Pellizzari 1978 Kanawha Valley, WV 0.08 Front Royal, VA 0.1 So. Charleston, WV <0.08 Birmingham, AL <0.1 Baton Rouge, LA <0.1 Upland, CA <0.1 Magna, VT 0.08 Grand Canyon, AZ 0.065 Geismar, LA 2.6 (max.) Niagara Falls, NY 1978 NS trace Detected in air outside 3 Barkley et al. of homes in Old Love 1980 Canal hazardous waste site (detection limit not stated) New Jersey NS NS NS 4 NPL sites and 1 muni- LaRegina et al. cipal landfill; detected in air samples collected at 3 of 5 sites; occurred in 75 to 100% of samples col- lected at these sites (de- tection limit >0.1 ppb) 1986 3HNSOdX3 NVWNH HOH TVILNILOd °S 3IN3IHLIOHOHOIa-2't 16 Table 5-2. Air Monitoring Data for 1,2-Dichloroethene (continued) Concentration Media Location Sampling date Isomer (ppb)? Comments Reference Ambient Air Edison, NJ NS trans 0.93 Brodzinsky and Singh 1982 Urban/suburban NS cis 0.068 (median) (669 sites) 3.5 (max) Source areas NS cis 0.3 (median) (101 sites) 6.7 (max) Pullman, WA December 1974 NS ND Detection limit 5 ppt Grimsrud and (rural area) to February 1975 Rasmussen 1975 Indoor air Niagara Falls, NY 1978 NS 0.015 Air in a basement of a Barkley et al. home in Old Love Canal 1980 Knoxville, TN Winter 1982 NS 8.1 (mean) Detected in 16 of 16 Gupta et al. 1984 samples (detection limit not stated) Landfill gas Selected U.S. landfills NS NS 70 (mean) Secondary source Vogt and Walsh 3,600 (max.) 1985 Municipal landfill February 1983to NS 210 (mean) Simulation Vogt and Walsh simulator February 1984 3,260 (max.) 1985 Long Island, NY NS trans 75,600 (max.) Air samples collected Lipsky and Jacot from methane vents at 2 1985 sanitary landfills California NS trans 59,000 (max.) 20 class Il landfills Wood and Porter 1987 8 Unless otherwise specified. ND = Not detected; NS = Not stated IHNSOdX3 NYWNH HO4 TVILNILOd °S 3N3IHL30HOTHOIa-2'+ 86 1,2-DICHLOROETHENE 99 5. POTENTIAL FOR HUMAN EXPOSURE 5.4.2 Water 1,2-Dichloroethene has been detected in surface, ground, and drinking waters, as well as in industrial and municipal effluents, urban runoff, and leachate from landfills throughout the United States. Table 5-3 shows the available monitoring data for 1,2-dichloroethene in these media. In some of the studies, only one of the 1,2-dichloroethene isomers was monitored; while in several of the studies the authors did not mention the specific isomer monitored. Concentrations of 1,2-dichloroethene detected in surface water ranged from 0.43 ppb in the Quinipiac River in Connecticut (Hall 1984) to 1,307.5 ppb in New Jersey (Table 5-3). 1,2-Dichloroethene has been detected in groundwater in several states and U.S. territories including Colorado, Connecticut, Florida, Maryland, Michigan, Nebraska, New Jersey, Pennsylvania, Puerto Rico, Washington, and Wisconsin (Table 5-3). Concentrations of 1,2-dichloroethene isomers detected in groundwater ranged from 0.25 to 0.28 ppb (range of average concentrations) from 6 areas near Miami, Florida (Singh and Orban 1987) to a maximum of 500,000 ppb in Southington, Connecticut (Hall 1984). Groundwater contamination has been reported at numerous waste disposal sites in the United States. In a detailed study, the Wisconsin Department of Natural Resources sampled groundwater at 20 municipal and 6 industrial landfills in Wisconsin. 1,2-Dichloroethene was detected in samples from 5 of 26 landfills at a maximum concentration of 3,900 ppb, and in leachate from 8 of 26 landfills at a maximum concentration of 310 ppb (Friedman 1988). Since 1,2-dichloroethene can be produced from biodegradation of a variety of VOCs, screening tests for VOCs or tests for such widely used solvents as TCE or PCE can provide useful screening tools for follow-up testing for 1,2-dichloroethene. For instance, a study of 19 landfill sites in Wisconsin showed that while the incidence of 1,2-dichloroethene in all test wells was 19%, approximately two-thirds of the wells showing detectable VOCs also showed detectable 1,2-dichloroethene (Battista and Connelly 1989). In a study of a western Connecticut manufacturing plant that used large quantities of high quality trichloroethylene for degreasing, it was found that 7 of 9 monitoring wells contained 1.2-320.9 ppb of trans-1,2-dichloroethene (Stuart 1983). More localized problems from leaking underground storage tanks or chemical spills may also show up in screens for VOCs (Stenzel and Gupta 1985). Where pollution levels are not excessive, remediation or permanent treatment technologies involving combinations of granular activated carbon or air stripping can remove over Table 5-3. Water Monitoring Data for 1,2-Dichloroethene Concentration Media Location Sampling Isomer (ppb) Comments Reference date Surface water ~~ Hylebos Waterway in the 1979 NS 0.8-2.4 Riley et al. 1980 Puget Sound Potomac River in Quantico, Spring 1986 trans <2 1 sample analyzed (detection limit Hall et al. 1987 VA not reported) 12 sites in the Delaware August 1979to NS ND Detection limit not reported Granstrom et al. and Raritan Canal in New January 1980 1984 Jersey Indian River in Vero Beach, May 1981 to NS ND 13 samples (detection limit 4.0 pg/L) Wang et al. FL May 1982 1985b Drainage canal discharging May 1981 to NS 4.0-48.1 Canal receiving contaminated Wang et al. into the Indian River in Vero May 1982 15.7 (mean) groundwater; detected in 23 of 39 1985b Beach, FL samples (detection limit 4.0 pg/L) New Jersey 1977-1979 trans 1307.5 (max.) Detected in 172 of 273 samples Page 1981 (detection limit not reported) Quinipiac River in 1980 trans 0.43 (mean) Detected in 4 of 5 samples Hall 1984 Southington, CT (detection limit not reported) Wilson Creek (adjacent to February 1979 NS 75 (max.) Stonebraker and hazardous waste site in Smith 1980 Bullit County, KY Groundwater 178 CERCLA sites 1981-1984 trans NS Frequency of detection = 29.1% Plumb 1987 (Comprehensive Environmental Repose, Compensation, and Liability Act) New Jersey 1977-1979 trans 818.6 (max.) Detected in 193 of 378 samples Page 1981 Wisconsin Sampling NS NS Detected in 5 of 1174 community Krill and Sonzogni results as of wells and 12 of 617 private wells 1986 June 30, 1984 (detection limit 1.0-5.0 pg/L) Wausau, Wi NS cis 83.3 Raw well water Hand et al. 1986 3HNSOdX3 NYIWNH HOA TVILN3LOd °S 3N3IHL30HOTHOIg-2't 00} Table 5-3. Water Monitoring Data for 1,2-Dichloroethene (continued) Concentration Media Location Sampling Isomer (ppb) Comments Reference date Wisconsin 1985-1987 NS 3,900 (max.) Detected at 5 of 26 sites Friedman 1988 Groundwater Montgomery County, MO 1983 trans 27-320 Detected in 4 samples Dever 1986 (cont.) 158 (mean) Southington, CT 1980 trans 50,000 (max.) Detected in 29 of 35 samples Hall 1984 16 (median) (detection limit not reported) Potomac-Raritan-Mogathy 1980-1982 trans NS Detected in 12 of 179 wells in the Fusillo et al. 1985 aquifer system (adjacent to outcrop area and not detected in 115 the Delaware River wells in the downdip of the outcrop (detection limit 1 pg/L) Nebraska Summer 1982 NS 2.1 (max.) Detected in 3 of 63 samples Goodenkauf and 0.50 (median) (detection limit 0.2 pg/L); private Atkinson 1986 wells Nebraska 1983-1984 NS 2.9 Detected in 1 of 97 samples; Goodenkauf and sources for public water system Atkinson 1986 Western CT manufacturing NS trans 1.2 to 320.9 Detected in 7 of 9 monitoring wells Stuart 1983 plant Biscayne aquifer, Miami, FL November 1982 trans 0.25-28 (range 12 total samples from 6 geographical Singh and Orban and March of average con- areas defined within the study area 1987 1983 centration fron the mix areas) Miami Drum Services in 1981 cis 839 (max.) Hazardous waste site Myers 1983 Miami, FL Biscayne aquifer in vicinity 1983 NS 19 (mean) Detected in 2 of 3 samples Myers 1983 of Miami Drum site (detection limit not reported) Piper Aircraft Corp. in Vero ~~ April 1981 to NS 1000-4000 At site of a leaking subsurface Wang et al. Beach, FL December 1983 trichloroethylene storage tank 1985a Lakewood, WA December 1983 trans 250-435 Detected in 11 of 11 samples; in the ~~ Wolf and Gorelik 330 (mean) vicinity of an NPL site 1984 3YNSOdX3 NVWNNH HOH VILN3LOd 'S INIHLIOHOTHOIa-2'+ 10} Table 5-3. Water Monitoring Data for 1,2-Dichloroethene (continued) Concentration Media Location Sampling Isomer (ppb) Comments Reference date Western Processing, Kings ~~ November 1982 trans Qualitatively Hazardous waste site Aldis et al. 1983 County, WA identified Groundwater Marshall landfill in Boulder NS trans 530 (onsite) NPL site EPA 1986f (cont.) County, CO 66 (offsite) Minnesota NS cis 0.5 - 20000 Detected in contaminated Sabel and Clark groundwater from 7 of 13 sites 1984 trans 0.6 to 98 Detected in contaminated groundwater from 3 of 13 sites Forest Waste Disposal site NS trans 100 (max.) NPL site EPA 1986b in Otisville, MI Lang Property site in NS trans 942 (mean) NPL site EPA 1987a Pemberton Township, NJ 2,500 (max.) Vega Alta Public Supply NS NS 74 (max.) NPL site; detected in 89 of 168 EPA 1988a Wells in Puerto Rico samples (detection limit not reported) Ponders Corner in Pierce 1984-1985 trans 85 (max.) NPL site EPA 1986¢ County, WA Hollinsworth Solderless 1983 NS 2,160 (max.) NPL site; level of dichloroethene EPA 1986d Terminal Co. in Fort (there was no indication whether this Lauderdale, FL was 1,1- or 1,2-dichloroethene) Lakewood Utility District NS trans 200 Production wells near a commercial Boateng et al. near Tacoma, WA facility 1984 Drinking water ~~ United States NS NS 2.0 (max.) Detected in samples collected from Westrick et al. (using ground- 16 of 466 randomly selected sites 1984 water sources) using groundwater as a raw water source (detection limit 0.2 pg/L) Drinking water ~~ Miami, FL NS trans 1 EPA 1980d JHNSOdX3 NYWNH HOH TVILN3ILOd 'S 3IN3H1L30HOIHOIg-2't colt Table 5-3. Water Monitoring Data for 1,2-Dichloroethene (continued) Concentration Media Location Sampling Isomer (ppb) Comments Reference date Drinking water Winnebago Co., IL NS trans ND - 64 5 homes tested Wehrmann 1985 (Private wells) (8 median) Drinking water ~~ Philadelphia, PA February 1975 NS NS Detected in 1 of 17 samples Suffet et al. 1980 (Private wells) to January (detection limit not reported) (cont.) 1977 5 U.S. cities 1975 cisand NS U.S. EPA National Organics EPA 1975a trans Reconnaissance Survey; cis isomer positively identified in samples from Miami, FL, Philadelphia, PA, and Cincinnati, OH; trans isomer positively identified in samples from Miami, FL Raw and 10 potable water treatment ~~ July 1982 to NS trace Positively identified in 3 raw and 3 Otson 1987 treated plants in Canada July 1983 treated water samples (detection drinking water limit not reported) Leachate 30 potable water treatment ~~ August 1979to NS raw water - 23 Positively identified in 2 raw and 11 Otson et al. 1982 plants in Canada December 1979 (max.) treated treated water samples water - 32 (max.) NS (landfill containing NS trans 45 - 800 Detected in 2 of 8 leachates Ghassemi et al. mixed industrial waste) (average (detection limit not reported) 1984 concentration of leachates) Minnesota NS cis 1.4 - 470 Detected in leachate from 5 of 6 Sabel and Clark sites (detection limit not reported) 1984 trans 3.8-88 Detected in leachate from 3 of 6 Sabel and Clark sites (detection limit not reported) 1984 Lyon, MN, municipal landfill NS trans 3.8 (mean) Brown and Donnelly 1988 34NSOdX3 NVYWNH HO4 TVILN3ILOd 'S 3INIHL3I0HOTHOIAZ €0l Table 5-3. Water Monitoring Data for 1,2-Dichloroethene (continued) Concentration Media Location Sampling Isomer (ppb) Comments Reference date Meeker, MN, municipal NS cis 190 (mean) Brown and landfill Donnelly 1988 Leachate trans 170 (mean) Brown and (cont.) Donnelly 1988 Rochester, MN, municipal NS cis 470 (mean) Brown and landfill Donnelly 1988 Rochester, MN, municipal NS trans 88 (mean) Brown and landfill Donnelly 1988 Wisconsin, 20 municipal 1985-1987 NS 310 Detected in leachate from 8 of 26 Friedman 1988 and industrial landfills sites Aqueous Forest Waste Disposal site NS trans 50 NPL site; estimate level (compound EPA 1986b lagoon in Otisville, MI detected below quantification limit) Urban storm 15 U.S. cities as of July 1982 trans 1-3 (in positive Detected in runoff from Little Rock, Cole et al. 1984 water runoff samples) AR, and Eugene, OR Waste water Los Angeles, CA NS NS 5.2 (mean) Effluent from a county sewage Gossett et al. treatment plant 1983 NS 1980/1981 trans untreated: 52-60 Municipal sewage treatment plant; Lao et al. 1982 effluent: 31-43 detected in 5 of 5 samples Chicago, IL NS trans <50 Effluent from a municipal sewage Lue-Hing et al. treatment plant 1981 NS NS trans 20 (max.) Treated effluent from a petroleum Snider and refinery Manning 1982 Owensboro, KY August 1975 cis NS Chemical plant effluent EPA 1976 Calvert City, KY October 1975 cis NS Chemical plant effluent EPA 1976 3HNSOdX3 NYIWNH HOH VILN3LOd °S 3N3H1304HO0THOIQ-2 vOol Table 5-3. Water Monitoring Data for 1,2-Dichloroethene (continued) Concentration Media Location Sampling Isomer (ppb) Comments Reference date United States NS Industry: EPA 1980d trans 10 (max.) coal mining trans 46 (max.) electrical electronic components trans 10 (max.) foundries trans 10 (max.) pharmaceutical manufacturing Waste water trans 75 (max.) nonferrous metals manufacturing (cont.) organic chemicals and trans 12 (mean) plastics manufacturing trans 190 (max.) paint and ink formulation trans <10 (max.) petroleum refining trans 290 (max.) rubber processing cis 1.6 steam electric (detected in 1 sample) Shackelford et al. 1983 cis 33 leather tanning (detected in 1 sample) cis 1400.8 (median) iron and steel manufacturing Shackelford et al. trans 2265.9 (median) (detected in 2 samples) 1983 cis 314.6 nonferrous metal (detected in 1 sample) United States NS cis 121.5 (median) organics and plastics [(detected in Shackleford et al. trans 14.6 (median) 2 samples) (cis) and 3 samples 1983 trans 3.9 (trans)] inorganic chemicals (detected in 2 samples) cis 8.3 textile mill (detected in 1 sample) cis 20.1 (median) plastics and synthetics (detected in 3 samples) cis 712.0 rubber processing 3HNSOdX3 NYWNH HOH TVILN3LOd 'S 3IN3IHL30HOTHOIa-2 tL Sol Table 5-3. Water Monitoring Data for 1,2-Dichloroethene (continued) Concentration Media Location Sampling Isomer (ppb) Comments Reference date trans 19.0 (median) [detected in 1 sample (cis) and 2 samples (trans)] trans 60.6 auto and other laundries (detected in 1 sample) Waste water cis 1.5 explosives (detected in 1 sample) (cont.) trans 3.9 trans 140.7 (medium) electronics (detected in 7 samples) trans 13.7 (median) mechanical products (detected in 2 Shackelford et al. samples) 1983 trans 29.3 transportation equipment (detected in 1 sample) trans 16.3 (median) publicly owned treatment works Shackelford et al. (POTW)(detected in 63 samples) 1983 NS NS trans 260 (mean) metal finishing EPA 1980b 1700 (max) trans 2200 (max) photographic equipment/supplies trans 75 (mean) non-ferrous metal manufacturing 260 (max) trans 150 (mean) rubber processing 290 (max) Rain water UCLA campus, Los 3/26/82 NS 0.230 1 sample Kawamura and Angeles, CA Kaplan 1983 ND = Not detected; NS = Not stated 3HNSOdX3 NVIWNH HO4 IVILNILOd 'S 3IN3HL30HOTHOIg-2'L 901 1,2-DICHLOROETHENE 107 5. POTENTIAL FOR HUMAN EXPOSURE 96% of VOCs such as cis-1,2-dichloroethene (Clark et al. 1988; Lee et al. 1988; Stenzel and Gupta 1985). In a comprehensive survey of United States drinking water derived from groundwater, 16 of 466 randomly selected sites and 38 of 479 purposely selected sites contained 1,2-dichloroethene. The maximum concentration was 2 ppb at random sites and 120 ppb at the nonrandom sites (Westrick et al. 1984). Trans-1,2-dichloroethene was found in Miami, Florida, drinking water at 1 ppb. Cis-1,2-dichloroethene was found in Miami drinking water at 16 ppb; and in Cincinnati, Ohio, and Philadelphia, Pennsylvania, drinking water at 0.1 ppb; but was not detected in 7 other drinking waters surveyed (EPA 1980d). In a four-city study (Cincinnati, Ohio; St. Louis, Missouri; Atlanta, Georgia; Hartford, Connecticut) to determine the major source type of priority pollutants in tap water and POTW influents, it was found that 43, 38, and 28% of commercial sources, industrial sources, and POTW influents, respectively, contained trans-1,2-dichloroethene (EPA 1981c). The average concentrations from the industrial sources were between 10 and 100 ppb while the others were <10 ppb. Industrial effluent monitoring data from Shackelford et al. (1983) was obtained from a database of a comprehensive EPA survey of 4,000 effluent samples from industries and POTWs. This survey was conducted in response to the consent decree between the National Resources Defense Council and the EPA on June 7, 1976. Data from this study are presented in Table 5-3. Over the last decade, the Safe Drinking Water Act has focussed attention on improved controls over VOC contamination (including 1,2-dichloroethene) of community drinking water systems. Based on available national statistics, 1,2-dichloroethene has been found in detectable concentrations at less than 5% of the community systems using surface water sources. The figures jumped to 21%, however, for community systems relying on groundwater (Coniglio et al. 1980). No comparable figures are available for noncommunity systems, such as truck stops or highway convenience stores in rural areas, or for domestic groundwater wells. 5.4.3 Sediment and Soil Available data on 1,2-dichloroethene in soil are limited to those obtained through hazardous waste site monitoring (Aldis et al. 1983; EPA 1986c, 1987a; Pennington 1983; VIAR 1987). Soil gas pollutants 1,2-DICHLOROETHENE 108 5. POTENTIAL FOR HUMAN EXPOSURE in a shallow, unconfined aquifer receiving waste water from metal-plating operations at Picattinny Arsenal in Morris County, New Jersey, were found to have a maximum cis-1,2-dichloroethene concentration of 33 ppb in the vadose zone (Smith 1988). 1,2-Dichloroethene has been detected, but not quantified, in sediment samples at Love Canal, New York (HSDB 1995). Recent summaries related to data on 1,2-dichloroethene in sediments have not been located. In the early 1980s, 1,2-dichloroethene was found at a concentration of >5 ppb (wet weight) in sediment at 4% of 361 stations reported in EPA's STORET database (Staples et al. 1985). No further summary information was located on the occurrence of 1,2-dichloroethene in sediments. EPA is in the process of consolidating all available information on toxics in sediments to comply with provisions of the Water Resources Development Act of 1992. This will lead to the creation of a National Sediment Inventory, which should eventually facilitate custom data retrievals and encourage research studies to analyze available sediment monitoring results (EPA 1993). 5.4.4 Other Environmental Media Trans-1,2-dichloroethene concentrations ranging from 22 to 55 g/L have been detected in municipal sludge from various treatment plants throughout the United States (Feiler et al. 1980: Naylor and Loehr 1982). Few reports exist of 1,2-dichloroethene in biota from U.S. waters. This is because 1,2-dichloroethene is not a typical biota contaminant (Staples et al. 1985). Nicola et al. (1987) reported mean and maximum 1,2-dichloroethene levels of 0.04 and 0.05 ppm, respectively, in fish tissue from Commencement Bay in Tacoma, Washington. No fish obtained at the 95 stations in EPA's STORET database contained detectable levels of 1,2-dichloroethene (Staples et al. 1985). A BCF of 6 was estimated for fathead minnows (ASTER 1995) using the method of Veith and Kosian (1983). Using a log octanol/water partition coefficient of 2.06 for trans-1,2-dichloroethene and a recommended regression equation (Lyman et al. 1982), a BCF of 22 has been estimated (HSDB 1995). Based on these estimated BCFs, 1,2-dichloroethene is not expected to bioaccumulate to any appreciable extent. 1,2-DICHLOROETHENE 109 5. POTENTIAL FOR HUMAN EXPOSURE 5.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE The general population is exposed to 1,2-dichloroethene in urban air and drinking water, with higher possibilities of exposure in community systems relying on groundwater supplies. Contaminated tap water can cause exposure via ingestion, inhalation, and dermal contact during showering and bathing. Inhalation is the most probable route of exposure. 1,2-Dichloroethene has been detected in urban air at average concentrations of 0.013-0.076 ppb (0.052-0.30 Ls) (EPA 1983a). These exposure levels correspond to an average daily intake of 1-6 pg 1,2-dichloroethene, assuming an average daily intake of 20 m> of air. Risks from inhalation exposures may be of more concern to populations in regions such as Gulf Coast states that have substantial production facilities for chlorinated polymers (Hall et al. 1989). An average daily intake of 0.5-5.4 ug from water is calculated assuming a concentration of 0.23-2.7 ppb (HSDB 1995). Data are insufficient for estimating 1,2-dichloroethene intake via other routes of exposure. Ashley et al.(1994) determined the internal dose of 32 volatile organic compounds in 600 or more people in the United States who participated in the Third National Health and Nutrition Survey (NHANES III). Detectable concentrations of cis- and trans-1,2-dichloroethene were found in fewer than 10% of the samples examined. Their detection limits were 0.013 and 0.014 ppb, respectively. According to a National Occupational Exposure Survey (NOES) conducted by NIOSH between 1981 and 1983, an estimated 215 workers in the United States are potentially exposed to 1,2-dichloroethene (mixture of cis and trans isomers); an estimated 61 workers in the United States are potentially exposed to cis-1,2-dichloroethene (NIOSH 1988). These tentative estimates will be updated as additional information on trade name compounds containing 1,2-dichloroethene becomes available. There was no NOES estimate for the trans isomer. Occupational exposure is by dermal contact with the vapor and liquid or by inhalation (HSDB 1995). Common operations in which there is potential industrial exposure to 1,2-dichloroethene include: use as a low-temperature solvent for heat-sensitive substances in extraction of caffeine, perfume oils, and fats from animal flesh; in rubber and dye industries in extraction and application; as a direct solvent in gums, waxes, etc.; in solvent mixtures for ester and ether derivatives, lacquers, resins, thermoplastics, and artificial fibers; in organic synthesis for polymers and telomeres; and in miscellaneous applications as a liquid dry cleaning agent, cleaning agent for printed circuit boards, food packaging adhesive, and germicidal fumigant (NIOSH/OSHA 1978). The extent of continuing use of 1,2-dichloroethene in these operations is unknown. 1,2-DICHLOROETHENE 110 5. POTENTIAL FOR HUMAN EXPOSURE Firefighters and workers at landfill sites may also be exposed to 1,2-dichloroethene (Michal 1976; NIOSH/OSHA 1978; Vogt and Walsh 1985). No information was located on exposure levels in other occupational settings. 5.6 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES Other than individuals who are occupationally exposed, populations with potentially high exposure include those living near production and processing facilities, hazardous waste sites, municipal waste water treatment plants, and municipal landfills. Near production and processing facilities, certain hazardous waste sites, and municipal landfills, potential exists for exposure to elevated levels of dichloroethene in air downwind of the sites and in contaminated drinking water from groundwater downgradient of the sites. Potential exposure levels cannot be estimated with the data available. 5.7 ADEQUACY OF THE DATABASE Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether adequate information on the health effects of 1,2-dichloroethene is available. Where adequate information is not available, ATSDR, in conjunction with the NTP, is required to assure the initiation of a program of research designed to determine the health effects (and techniques for developing methods to determine such health effects) of 1,2-dichloroethene. The following categories of possible data needs have been identified by a joint team of scientists from ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would reduce the uncertainties of human health assessment. This definition should not be interpreted to mean that all data needs discussed in this section must be filled. In the future, the identified data needs will be evaluated and prioritized, and a substance-specific research agenda will be proposed. 5.7.1 Identification of Data Needs Physical and Chemical Properties. The physical and chemical properties of both cis- and trans-1,2-dichloroethene are well characterized (see Table 3-2) and allow prediction of the transport 1,2-DICHLOROETHENE 111 5. POTENTIAL FOR HUMAN EXPOSURE and transformation of the chemicals in the environment. Therefore, no data needs have been identified at this time. Current production and import/export volumes and usage data are presently unavailable in the literature. Much of the information regarding 1,2-dichloroethene may be difficult to obtain because many manufacturing companies maintain confidentiality. In 1977, the estimated production of cis-1,2-dichloroethene was 500 metric tons. No information was available for the trans isomer or for the mixture (HSDB 1995). Also, information about future domestic production, and past, present and future imports and exports is lacking. Furthermore, determining the percentage of 1,2-dichloroethene that is used as a captive intermediate (i.e., the 1,2-dichloroethene consumed in closed proces$es in which the compound is not isolated), as opposed to its use as a solvent, is critical to estimating the amount released to the environment. Differences in toxicity and environmental fate also suggest that isomer-specific information on use and consumption is important. Determination of the levels of 1,2-dichloroethene in consumer products is essential for estimating the exposure of the general population. With up-to-date and accurate production, import/export, and use data, the extent of release into the environment and the potential for human exposure could be more realistically determined. Disposal methods have been described and appear to be satisfactory. Because the EPA identified trans-1,2-dichloroethene as a hazardous waste, its disposal is regulated under the Resource Conservation and Recovery Act (RCRA). Specific information on federal regulations concerning hazardous waste disposal by land treatment, landfilling, incineration, thermal treatment, chemical/physical/biological treatment, underground injection, and deep sea injection appears in the Code of Federal Regulations (40 CFR 190 to 399). Release of trans-1,2-dichloroethene in waste water is regulated under the Clean Water Act by the National Pollutant Discharge Elimination System (NPDES). Information regarding effluent guidelines and standards for trans-1,2-dichloroethene can be found in 40 CFR 122, 40 CFR 125, 40 CFR 413.02(i), 40 CFR 414, and 40 CFR 433.11(e). Environmental Fate. 1,2-Dichloroethene released to the environment partitions mainly to the atmosphere (Eisenreich et al. 1981; Swann et al. 1983; Thomas 1982). It is primarily found in the atmosphere and groundwater (HSDB 1995; TRI93 1995). Important sources of 1,2-dichloroethene include industrial releases and degradation products from other solvents such as trichloroethene, 1,2-DICHLOROETHENE 112 5. POTENTIAL FOR HUMAN EXPOSURE tetrachlorethene, and vinyl chloride (Parsons et al. 1984; Shen 1982b; Smith and Dragun 1984; Vogel et al. 1987). 1,2-Dichloroethene isomers have predicted atmospheric half-lives of 12 days (cis) and 5 days (trans) (Goodman et al. 1986). Both isomers react with hydroxyl radicals in the atmosphere, forming formyl chloride, but atmospheric ozone, nitrate radicals and singlet oxygen have little environmental effect (Atkinson and Carter 1984). In surface waters, the isomers of 1,2-dichloroethene are rapidly volatized; half-lives of 5-6.2 hours are estimated for water 1 m deep (Dilling 1977). The compound is not significantly bound to soils or sediments (Barber et al. 1988). Soil-groundwater degradation processes are anaerobic and may involve multiple pathways. Additional information about the long-term atmospheric fate would be useful, because of the importance of this pathway and the uncertainty of atmospheric degradation processes. Bioavailability from Environmental Media. No specific information is available regarding human inhalation, oral, or dermal absorption of 1,2-dichloroethene from air, water, food, or soil. Exposure via contaminated drinking water is particularly relevant to humans. Since 1,2-dichloroethene is a neutral lipophilic chemical with a low molecular weight, it probably is readily absorbed through the lungs and gastrointestinal tract. The few available toxicity studies of animals exposed to 1,2-dichloroethene support this contention (Filser and Bolt 1979; Gargas et al. 1988, 1989). No information about human exposure to 1,2-dichloroethene in the environment and the resulting concentrations in human tissue was located. Studies of absorption of 1,2-dichloroethene from air, water, food, and soil in contaminated environments near hazardous waste sites would allow for determination of the rate and extent of absorption from each of these media and for comparison of the potential hazards posed by 1,2-dichloroethene within these media. Food Chain Bioaccumulation. Few data are available describing the food chain bioaccumulation of 1,2-dichloroethene. Experimental data are unavailable; therefore, it is not known if the bioconcentration potential is consistent with estimated values obtained from regression equations. The estimated BCF of 6 for fathead minnows (ASTER 1995; Veith and Kosian 1983) suggests that the potential for 1,2-dichloroethene to bioconcentrate is low for aquatic organisms. Therefore, further studies on bioaccumulation are not recommended. However, biomagnification studies would enable scientists to assess the dangers of human exposure to 1,2-dichloroethene from fish and seafood. Data describing exposure levels in air, surface water, drinking water, groundwater, and soil are limited. 1,2-Dichloroethene has been detected in urban and rural air, air near hazardous waste sites, and indoor 1,2-DICHLOROETHENE 113 5. POTENTIAL FOR HUMAN EXPOSURE air (Grimsrud and Rasmussen 1975; Lipsky and Jacot 1985; Shah and Singh 1988; Vogt and Walsh 1985). Where it is used as a dry cleaning agent and in the manufacture of other chemicals, indoor air concentrations of 1,2-dichloroethene are likely to be greater than concentrations in outdoor air. Information concerning the number of persons potentially exposed to 1,2-dichloroethene near waste sites, manufacturing and production facilities, and use facilities, however, is not available. In these areas and in areas of widespread use, the potential for human exposure is high. Monitoring data that showed the existence of 1,2-dichloroethene in food could not be located. 1,2-Dichloroethene has been detected infrequently in drinking water supplies. Reliable estimates of human intake of 1,2-dichloro- ethene via air, water, and food are not available. Therefore, it is recommended that further studies on human intake of 1,2-dichloroethene from air, water, and food, particularly around hazardous waste sites, be undertaken. Exposure Levels in Humans. 1,2-Dichloroethene is not a naturally occurring substance. Monitoring data pertaining to the presence of 1,2-dichloroethene in human urine, breast milk, blood, or adipose tissue were not located in the available literature. Information on biological media monitoring of the general populations, particularly populations near waste sites, is necessary for assessing the need to conduct health studies on these populations. Exposure Registries. No exposure registries for 1,2-dichloroethene were located. This substance is not currently one of the compounds for which a subregistry has been established in the National Exposure Registry. The substance will be considered in the future when chemical selection is made for subregistries to be established. The information that is amassed in the National Exposure Registry facilitates the epidemiological research needed to assess adverse health outcomes that may be related to exposure to this substance. Production, Import/Export, Use, Release, and Disposal. According to the Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C. Section 11023, industries are required to submit substance release and off-site transfer information to the EPA. The Toxics Release Inventory (TRI), which contains this information for 1993, became available in 1995. This database will be updated yearly and should provide a list of industrial production facilities and emissions. Exposure Levels in Environmental Media. Reliable monitoring data for the levels of 1,2-dichloroethene in contaminated media at hazardous waste sites are needed so that the information 1,2-DICHLOROETHENE 114 5. POTENTIAL FOR HUMAN EXPOSURE obtained on levels of 1,2-dichloroethene in the environment can be used in combination with the known body burden of 1,2-dichloroethene to assess the potential risk of adverse health effects in populations living in the vicinity of hazardous waste sites. 5.7.2 Ongoing Studies As part of the Third National Health and Nutrition Evaluation Survey (NHANES III), the Environmental Health Laboratory Sciences Division of the National Center for Environmental Health, Centers for Disease Control and Prevention, will be analyzing human blood samples for 1,2-dichloro- ethene and other volatile organic compounds. These data will give an indication of the frequency of occurrence and background levels of these compounds in the general population. No studies on the environmental fate of 1,2-dichloroethene are in progress. NIOSH is now updating its occupational exposure estimates with additional information about exposure to trade name compounds. No other ongoing studies that would address data needs on general population and worker exposure to 1,2-dichloroethene were found. 1,2-DICHLOROETHENE 115 6. ANALYTICAL METHODS The purpose of this chapter is to describe the analytical methods that are available for detecting, and/or measuring, and/or monitoring 1,2-dichloroethene, its metabolites, and other biomarkers of 1,2-dichloro- ethene exposure and effect. The intent is not to provide an exhaustive list of analytical methods. Rather, the intention is to identify well-established methods that are used as the standard methods of analysis. Many of the analytical methods used for environmental samples are the methods approved by federal agencies and organizations such as EPA and the National Institute for Occupational Safety and Health (NIOSH). Other methods presented in this chapter are those that are approved by groups such as the Association of Official Analytical Chemists (AOAC) and the American Public Health Association (APHA). Additionally, analytical methods are included that modify previously used methods to obtain lower detection limits, and/or to improve accuracy and precision. To determine dichloroethenes in various matrixes, most approaches involve purge procedures. Since these analytes are volatile (bp: 60.3 °C cis; 48.0-48.5 °C trans), removing them from an often complex matrix has very distinct advantages, particularly for biological and environmental samples. Virtually all standard methods use purge and trap procedures, in which the compounds are volatilized by passing an inert gas through a sample solution or suspension and the purged components are trapped on a solid sorbent for subsequent removal and analysis by gas chromatography (GC). Because of the presence of halogens, dichloroethenes can be selectively detected using devices such as electron capture, Hall electrolytic conductivity, or photoionization detectors. The most common detection technique specified by the standard methods is mass spectrometry (MS), which can readily achieve a high degree of selectivity and sensitivity. 6.1 BIOLOGICAL SAMPLES Methods of analysis for 1,2-dichloroethene in biological materials are presented in Table 6-1. The purge and trap method of Lin et al. (1982) is a suitable method for extraction and measurement of cis- and trans-1,2-dichloroethene in body tissues. However, recovery of trans-1,2-dichloroethene varies with the type of body tissue. This finding generally agrees with those of the investigators who have attempted to measure levels of volatile halocarbons in body tissues. In addition to purge and trap, the headspace analysis methods of Hara et al. (1980) and Uehori et al. (1987) allow qualitative Table 6-1. Analytical Methods for Determining 1,2-Dichloroethene in Biological Samples Sample Analytical detection Percent Sample matrix Preparation method method limit recovery Reference Adipose, kidney, and Mince and purge tissue at 60 °C; GC/HECD 50 pg 93.3+12.4% (adipose) Lin et al. 1982 brain tissue trap on Tenax; thermal desorption 53.4+2.43 (kidney) 62.6+2.62 (brain) Blood Heat in a closed vial GC/FID No data No data Uehori et al. 1987 Blood Mix with water; heat in a closed GC/MS 10-20 pg No data Hara et al. 1980 vial at 40 °C; headspace analysis Blood Purge and trap with antifoaming GC/MS 20 ppt ~ 125 Ashley et al. 1992 agent; thermal desorption Blood, urine, solid tissue ~~ Sample in sealed vial heated to GC/FID No data No data Streete et al. 1992 65 °C; headspace analysis GC/ECD Body tissue Homogenize and mix tissue with GC/MS 10-20 pg No data Hara et al. 1980 water; heat in a closed vial at 40 °C; headspace analysis Breath Portable spirometer into canisters GC/MS No data 99 (trans) Raymer et al. 90 (cis) 1990 For trans-1,2-dichloroethene ECD = electron capture detector; FID = flame ionization detector; GC = gas chromatography; HECD = Hall electroconductivity detection; MS = mass spectrometry : 3IN3IHL30HOTHOIa-2 + SAOHL3NW TVOILATVNY ‘9 9Ll 1,2-DICHLOROETHENE 117 6. ANALYTICAL METHODS identification of 1,2-dichloroethene in biological materials. A combination of detectors enabled Streete et al. (1992) to determine dichloroethenes in the headspace of blood, urine, and solid tissues. Dichloroethenes in breath can be determined by GC/MS after collection with a portable spirometer (Raymer et al. 1990). In this approach, recoveries exceeded 90% for the dichloroethene isomers. The detection limit for dichloroethenes in human blood has been extended to part-per-trillion levels by Ashley et al. (1992), using an automated purge and trap technique that suppresses sample foaming with an antifoaming agent. High resolution GC/MS can be used to enhance the contaminant separation abilities of gas chromatography on blood samples (Ashley et al. 1992; Bonin et al. 1992). 6.2 ENVIRONMENTAL SAMPLES Analytical methods for determining cis- and trans-1,2-dichloroethene in environmental samples are presented in Table 6-2. Analysis of 1,2-dichloroethene in workplace air samples can be determined by NIOSH method 1003 (NIOSH 1987). Methodologies appearing in the literature for sampling 1,2-dichloroethene in air are essentially the same with minor variations. Capillary columns are versatile in separating contaminants of interest, and usually offer superior resolution and limits of detection (Oxenford et al. 1989). Various detectors are used, such as flame ionization detectors (FID), electron capture detectors (ECD), Hall electroconductivity detectors (HECD), and mass spectrometers. Multiple detectors are often employed in series or in parallel to increase the number and types of compounds detectable by purge and trap methods (Ho 1989; Kessels et al. 1992). Of the four listed, the FID is the least sensitive to halogenated hydrocarbons, yet it is sensitive enough for environmental samples. For 1,2-dichloroethene, adsorption to the solid sorbent is a significant analytical concern because of its volatility. It may be difficult to completely remove highly volatile compounds such as 1,2-dichloro- ethene from the air stream. Solid sorbents other than charcoal appear in some analytical methods; the most popular is the resin, Tenax® GC. In addition to Tenax, Mehran et al. (1990) used Carbosieve® with capillary chromatography to decrease the analysis time for EPA method 502.2. Pollack and co- workers (1991) provide for automating the collection and analysis of cis-1,2-dichloroethene by focusing the sample on a trap consisting of Carbopack-B and Carbosieve S-III instead of on glass beads. Substituting spray and trap for purge and trap enhances extraction efficiencies by a factor of 2-5 and eliminates difficulties associated with sample foaming (Matz and Kesners 1993). Table 6-2. Analytical Methods for Determining 1,2-Dichloroethene in Environmental Samples Sample Analytical method detection Percent Sample matrix Preparation method limit recovery Reference Air Charcoal tube collection and CS, GC/FID 16 ppm No data NIOSH 1987 desorption Air Stainless steel canister (modified =~ GC/MS 0.3 ppb (cis) No data McClenny et al. 1991 EPA method TO-14) Air Gas sampling loop" Fast GC/FID 4.3 ppb (cis) No data Ke et al. 1992b Drinking water Purge and trap onto adsorbent; GC/HECD 0.002 pg/L 8017 EPA 1986e backflush to cryogenically-cooled trap Drinking water Automated purge and trap; GC/PID; No data No data Ho et al. 1989 thermal desorption GC/HECD (capillary) Drinking water Purge and trap (modified EPA GC/ITD <0.2 pg/L 100 (cis) Eichelberger et al. 1990 method 524.2) (capillary) 92 (trans) Drinking water Purge and trap (modified EPA GC/FID; 0.01 pg/L 100 (trans) Kessels et al. 1992 method 524.2) GC/ECD (trans)® 99 (cis) (capillary) 0.03 pg/L (cis)? Water Purge and trap; thermal GC/MS (method 1.6 pg/L 1.05C+0.03P APHA/AWWA/WEF desorption 6210) (trans) (trans) 1992 (Standard Methods) Water Purge and trap onto adsorbent; GC/HECD 0.10 pg/L 0.97C-0.16 (trans) APHA/AWWA/WEF thermal desorption (method 6230) (trans) 1992 (Standard Methods) Water Flow injection MIMS (uses ion 0.5 ppt (trans) No data Bauer and Solyom 1994; trap MS) Soni et al. 1995 Groundwater, soil, Purge and trap onto adsorbent; GC/MS (Sws46 5 pg/L 1.05C+0.03 EPA 1986 sediment, solid waste thermal desorption method 8240B) (trans) Groundwater, soil, Purge and trap onto adsorbent; GC/MS (SW846 60 ng/L (trans), 120 9315.2 (trans), EPA 1986 sediment, solid waste thermal desorption method 8260A) ng/L (cis) 1016.7 (cis) SAOHL3W TVOILATYNY 9 IN3IHL3OHOTHOIQ-2'L gli Table 6-2. Analytical Methods for Determining 1,2-Dichloroethene in Environmental Samples (continued) Sample Analytical method detection Percent Sample matrix Preparation method limit recovery Reference Groundwater, soil, Purge and trap onto adsorbent; GC/HECD 2 ng/L (optimum 0.97C-0.16 (trans) EPA 1986 sediment, solid waste thermal desorption (SW846 method conditions for trans) 8010B) Groundwater, soil, Purge and trap onto adsorbent; GC/PID 50 ng/L (trans) 93+3.7 (trans) EPA 1986 sediment, solid waste thermal desorption GC/HECD 60 ng/L (trans) 9913.7 (trans) (SW846 method 8021A) Wastewater Purge and trap onto adsorbent; GC/HECD 0.1 pg/L 91+19 EPA 1982 backflush to cryogenically-cooled (EPA 601) trap Wastewater Purge and trap onto adsorbent; GC/MS 1.6 pg/L 99112 EPA 1982 backflush to cryogenically-cooled (EPA 624) trap Wastewater Purge and trap (EPA Master GC/MS ~1 ppb No data Michael et al. 1991 Analytical Scheme) (capillary) Landfill leachate Homogenized sample; heated at GC/MS (qual.) ~1 ppb No data Forst et al. 1989 40 °C; headspace sampled GC/FID (quant.) Soil Purge and trap onto adsorbent; GC/MS 5 pg/kg No data EPA 1987b rapid heating desorption Food Headspace with solid-phase GC/HECD ~100 pg/kg No data Page and Lacroix 1993 microextraction Food Homogenize sample in alcohol GC/MCD No data No data AOAC 1990a 38eCD bThis formula has concentration entered as pg/L in place of C (true concentration) then calculated as a percentage. Example: For 0.97C-0.16 at a concentration of 10 pg/L: (0.97x10) - 0.16 = 9.54. 9.54 of 10 is equivalent to 95.4% recovery. AOAC = Association of Official Analytical Chemists; APHA = American Public Health Association; AWWA = American Water Works Association; ECD = electron capture detection; EPA = Environmental Protection Agency; FID = flame ionization detection; GC = gas chromatography; HECD = Hall electrolytic conductivity detection; ITD = ion trap detection; MCD = microcoulometric detection; MIMS = membrane introduction mass spectrometry; MS = mass spectrometry; NIOSH = National Institute of Occupational Safety and Health; PID = photoionization detection; WEF = Water Environment Federation SAOHL3N TVOILATVYNY 9 3N3HL30HOHOIa-2 + 611 1,2-DICHLOROETHENE 120 6. ANALYTICAL METHODS EPA method 601 (purgeable halocarbons) and EPA method 524 (purgeables) describe analysis of 1,2-dichloroethene in municipal and industrial waste water (EPA 1982). In both methods, a 5 mL grab sample of water is connected to a purging chamber. This chamber allows an inert gas to bubble through the water sample; the gas flow is directed through an adsorbent tube. In EPA method 601, nitrogen or helium is the purging gas, and the adsorbent column consists of two different adsorbents and a drying agent. In EPA method 624, helium is the purging gas, and the adsorbent column is made up of one adsorbent and a drying agent. The collected organics are liberated from the sorbent by heating the sorbent column while backflushing with an inert gas; these organics are then introduced into the gas chromatograph. EPA methods 601 and 624 were developed to analyze volatile priority pollutants. In EPA method 601, analysis by GC uses a Carbopack B column, a Poracil C column, and a HECD detector. In EPA method 624, analysis by GC uses a Carbopack B column and a mass spectrometer. Since trans-1,2-dichloroethene is a priority pollutant and cis-1,2-dichloroethene is not, only the trans isomer is mentioned in this method. EPA method 502.1 is used to analyze 1,2-dichloroethene in finished or raw source water (EPA 1986¢). This method is similar to EPA method 601. However, once the compound has been purged from the water sample to the adsorbent tube, the compound is introduced to the gas chromatograph by rapidly heating the adsorbent tube, with no intermediate cryogenic trapping. Numerous researchers have applied modifications of the EPA methods to environmental samples. EPA's Master Analytical Scheme (Michael et al. 1991) incorporates automated purge and trap and capillary chromatography into method 624 to achieve sensitivity of 1 ppb. Method 624 was compared to purgeable organic chloride analysis by Barber et al. (1992) and found to be superior by virtue of its contaminant identification capabilities. Eichelberger et al. (1990) modified method 524 by using a capillary column and an ion trap detector (ITD) to achieve detection levels below 200 ppt. Headspace sampling coupled with capillary GC/MS offers a promising screening tool since it requires minimal sample preparation (Gryder-Boutet and Kennish 1988). Headspace GC/MS can also been used for determining dichloroethenes in landfill leachate (Forst et al. 1989). Purge and trap methodology sometimes involves direct trapping of the bubbled compound cryogenically. Water contamination can become a problem in this method. The cryogenic trap described in EPA methods 601 and 624 is a specialized item and may not be adaptable to all gas 1,2-DICHLOROCETHENE 121 6. ANALYTICAL METHODS chromatographs. The considerations discussed above regarding use of different columns and detectors also apply here. The EPA guidelines for contract laboratories include methodology for water and soil sample analysis (EPA 1987c). The method listed in Table 6-2 is identical to EPA method 502.1 for the purpose of this discussion (except for the use of a mass spectrometer as the detector). The procedure for analyzing low-level contamination in soil is also similar to EPA method 502.1, except that the purging gas passes through a soil sample rather than a water sample. For higher-level soil contamination, the soil sample is first extracted with methanol. An aliquot of the extract is diluted with water; then the purge and trap methodology is followed. With respect to dichloroethene recoveries, Hewitt et al. (1991) found a headspace technique that is comparable to EPA SW-846 method 8240 for soil. It is practical for sample screening where contaminant identities were not required. The various SW-846 methods for 1,2-dichloroethene presented in Table 6-2 are similar except for detection method. EPA method TO-14 uses an evacuated stainless steel canister to collect ambient air samples. Sample aliquots are analyzed by GC/MS. McClenny et al. (1991) report a method detection limit of 0.3 ppb for this method. A method which represents a significant departure from more traditional methods for environmental samples is solid-phase microextraction (SPME). Solid phase microextraction uses a coated fused-silica fiber to collect contaminants from air and water samples. Chai et al. (1993) describe a simple non-purge and trap technique for determining dichloroethenes in air and water using this approach. The contaminants on the coated fused-silica fiber can then be thermally desorbed directly into the gas chromatograph for analysis. Page and Lacroix (1993) show the utility of headspace sampling coupled with fused-silica fiber adsorption in determining dichloroethenes at the 100 ppt level in foods. Their method satisfies the detection limit requirements of EPA method 524.2 for chloroethenes. Bauer and Solyom (1994) have developed a method to directly analyze waters in an ion trap mass spectrometer and have achieved a limit of detection for trans-1,2-dichloroethene of 0.5 ppt using single ion monitoring of m/z 96 (Soni et al. 1995). 6.3 ADEQUACY OF THE DATABASE Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the Administrator of EPA and agencies and programs of the Public Health Service) to assess whether adequate information on the health effects of 1,2-dichloroethene is available. Where adequate 1,2-DICHLOROETHENE 122 6. ANALYTICAL METHODS information is not available, ATSDR, in conjunction with the NTP, is required to assure the initiation of a program of research designed to determine the health effects (and techniques for developing methods to determine such health effects) of 1,2-dichloroethene. The following categories of possible data needs have been identified by a joint team of scientists from ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would reduce the uncertainties of human health assessment. This definition should not be interpreted to mean that all data needs discussed in this section must be filled. In the future, the identified data needs will be evaluated and prioritized, and a substance-specific research agenda will be proposed. 6.3.1 Identification of Data Needs Methods for Determining Biomarkers of Exposure and Effect. The available database provides several analytical methods adequate for the measurement of cis- and trans-1,2-dichloroethene in body tissue (see Section 6.1). Accuracy measurements for 1,2-dichloroethene by Lin et al. (1982) show excellent recovery from adipose tissue but marginal recoveries from kidney and brain tissues. 1,2-Dichloroethene was recovered at 88—150% from blood (Ashley et al. 1992). Limits of detection for all biological matrices ranged from 10 to 50 pg. Additional recovery data in all condensed biological media are needed. Other than the parent compounds, there are no known biomarkers of exposure or the effects of exposure that are unique to 1,2-dichloroethene. Consequently, biomarkers of exposure or the effect of exposure should be identified; standardized analytical methods for their determination should be identified or developed in response. These biomarkers could allow an easier route for identification of exposure, especially for some tissues where bioconcentration of 1,2-dichloroethene does not occur. Methods for Determining Parent Compounds and Degradation Products in Environmental Media. Numerous analytical methods exist for analysis of cis- and trans-1,2-dichloroethene in environmental matrices (see Section 6.2). These analytical methods may be used to identify areas of 1,2-dichloroethene contamination, and to determine the potential threat to human health of 1,2-dichloroethene in the environment. Standardized methods exist for the analysis of drinking water, waste water, soil and air (APHA 1992; EPA 1986, 1987b; NIOSH 1987). Standardized methods for analyzing other media such as sediments and surface water will aid in establishing levels of human exposure to 1,2-dichloroethene. Inhalation is the most probable route of 1,2-DICHLOROETHENE 123 6. ANALYTICAL METHODS exposure, and atmospheric exposure is likely to be of greatest concern to humans. However, the standardized methods for detecting 1,2-dichloroethene in air appear to be weak. For example, its detection limit of 16 ppm, outlined by the NIOSH technique (NIOSH 1987), is relatively high. Conversely, the stainless steel canister method of McClenny et al. (1991) purports to have a detection limit of 0.3 ppb and although not rigorously standardized, shows promise in detecting ambient background levels of 1,2-dichloroethene. Information regarding the recovery efficiencies of the NIOSH (1987), McClenny (1991), and Ke et al. (1992b) procedures for detecting 1,2-dichloroethene in air were lacking. Additional data is needed to assess both accuracy and precision in the analysis of 1,2-dichloroethene in air. Contamination of surface water, groundwater, and foods in the vicinity of waste sites poses a threat to humans through oral exposure to 1,2-dichloroethene. Near quantitative recoveries and <0.02 ppb detection limits were reported by Eichelberger et al. (1990). Low part-per-trillion detection limits were reported by Kessels et al. (1992) and an 0.5 ppt detection limit was reported by Soni et al. (1995). These recoveries and detection limits for 1,2-dichloroethene in water, coupled with the specificity offered by capillary gas chromatography and selective detection used by these researchers provide a means for determining 1,2-dichloroethene at very low levels in water. Currently, no viable method exists for determining 1,2-dichloroethene in food. The detection limit of 100 pg/kg reported by Page and Lacroix (1993) is at least two orders of magnitude higher than what is required to be comparable to existing air and water methods for 1,2-dichloroethene. Appreciable additional work is needed in this area. 6.3.2 Ongoing Studies The Environmental Health Laboratory Sciences Division of the National Center for Environmental Health, Centers for Disease Control and Prevention, is developing methods for the analysis of both cis- and trans-1,2-dichloroethene and other volatile organic compounds in blood. These methods use purge and trap methodology, high resolution gas chromatography, and magnetic sector mass spectrometry which gives detection limits in the low parts per trillion (ppt) range. Ongoing studies for developing new analytical methods for 1,2-dichloroethene in environmental matrices could not be located. 1,2-DICHLOROETHENE 125 7. REGULATIONS AND ADVISORIES The international, national, and state regulations and guidelines regarding 1,2-dichloroethene in air, water, and other media are summarized in Table 7-1. ATSDR has derived an MRL of 0.2 ppm for both acute-duration inhalation exposure (14 days or less) and intermediate-duration inhalation exposure (15-365 days) to trans-1,2-dichloroethene based on a study by Freundt et al. (1977) that found fatty degeneration of the liver. The acute MRL is based on an LOAEL of 200 ppm over an 8-hour period, and the intermediate MRL is based on an LOAEL of 200 ppm for 8 hours per day, 5 days per week for 8 or 16 weeks. ATSDR has derived oral MRLs for both acute- and intermediate-duration exposure. For acute oral exposure, data supported the derivation of an MRL for cis-1,2-dichloroethene of 1 mg/kg/day; however, no acute-duration MRL was derived for trans-1,2-dichloroethene. The acute oral MRL for cis-1,2-dichloroethene is based on a study by McCauley et al. (1990) that found hematological effects at 290 mg/kg/day and reported a NOAEL of 97 mg/kg/day. Intermediate-duration oral exposure MRLs were derived for both the cis and trans isomers. The intermediate duration oral MRL for cis-1,2-dichloroethene is 0.3 mg/kg/day based on a hematological study (McCauley et al. 1990). For trans-1,2-dichloroethene, the intermediate oral MRL is 0.2 mg/kg/day, based on hepatic effects (Barnes et al. 1985). EPA has given cis-1,2-dichloroethene a non-cancer rating or a “not classifiable” rating (D) (IRIS 1995). No National Toxicology Program (NTP) or IARC classifications exists. OSHA requires employers of workers who are occupationally exposed to a mixture of trans- and cis-1,2-dichloroethene (CAS No. 540-59-0) to institute engineering controls and work practices to reduce exposure to and maintain employee exposure at or below permissible exposure limits (PEL). The employer must use engineering and work practice controls, if feasible, to reduce exposure to or below an 8-hour time-weighted average (TWA) of 200 ppm (790 mg/md). Respirators must be provided during the time period necessary to install or implement feasible engineering and work practice controls (OSHA 1989). 1,2-DICHLOROETHENE 126 7. REGULATIONS AND ADVISORIES 1,2-Dichloroethene is regulated by the Clean Water Effluent Guidelines as stated in Title 40, Section 400-475, of the Code of Federal Regulations. The point source category for which 1,2-dichloroethene is controlled as a Total Toxic Organic is electroplating (EPA 1981). The Resource Conservation and Recovery Act (RCRA) identifies 1,2-dichloroethene as a hazardous waste when it is discarded as a commercial chemical product, off-spec species, container residue, or spill residue (EPA 1980a). 1,2-DICHLOROETHENE 7. REGULATIONS AND ADVISORIES 127 Table 7-1. Regulations and Guidelines Applicable to trans- and cis-1,2-Dichloroethene Agency Description Information Reference trans cis INTERNATIONAL WHO NAp NAp IARC Group (cancer ranking) None None NATIONAL Regulations: a. Water: . EPA/OW Ambient Water Quality Criterion 1.16x10*4 3.3x102 ug/L IRIS 1995 pg/L (human 45 FR 79318 (aquatic health) (11/28/80) organisms) Method 601-Purgeable Halocarbons Yes NAp 40 CFR 136 EPA 1973 Method 624-Purgeables Yes NAp 40 CFR 136 EPA 1973 Method 1624 Revision B - Volatile Organic Yes NAp 40 CFR 136 Compounds by Isotope Dilution GC/MS EPA 1973 Hazardous Waste Injection Restrictions Yes NAp 40 CFR 148 (Proposed rule) 60 FR 11702 EPA 1995 EPA-ODW Public Notification Yes NAp 40 CFR 141.32 EPA 1975a Maximum Contaminant Levels for Organic 0.1 mg/L 0.1 mg/L 40 CFR 141.61 Contaminants EPA 1975a b. Other: CPSC Consumer product limits Nap NAp EPA/OERR Reportable Quantity 1,000 Ib. NAp 40 CFR 302.4 EPA 1985 EPA/OSW Municipal Solid Waste Landfills: Appendix | - Yes Yes 40 CFR 258 Constituents for Detection Monitoring EPA 1991 Municipal Solid Waste Landfills: Appendix Il - ~~ 0.5-5 pg/L same 40 CFR 258 List of Hazardous Inorganic and Organic (Practical EPA 1991 Constituents Quantitation Limits for 3 Methods) Discarded Commercial Chemical Products, Yes NAp 40 CFR 261.33 Off-specification Species, Container EPA 1980a Residues, and Spill Residues Thereof Identification and Listing of Hazardous Yes NAp 40 CFR 261 Wastes: Appendix VIII - Hazardous EPA 1980a Constituents Standards for Owners and Operators of 1-5 ug/L NAp 40 CFR 264 Hazardous Waste Treatment, Storage, and (Practical EPA 1980 Disposal Facilities: Appendix IX - Ground- Quantitation water Monitoring List Limits for 2 Methods) 1,2-DICHLOROETHENE 128 7. REGULATIONS AND ADVISORIES Table 7-1. Regulations and Guidelines Applicable to trans- and cis-1,2-Dichloroethene (continued) Agency Description Information Reference trans cis NATIONAL (cont.) Treatment Standards - Applicability Yes Nap 40 CFR 268.40 EPA 1987 Treatment Standards Expressed as Waste 0.054 mg/L NAp 40 CFR 268.43 Concentrations (waste EPA 1988 waters); 33 mg/kg (non- waste waters) Land Disposal Restrictions: Appendix III - Yes NAp 40 CFR 268 List of Halogenated Organic Compounds EPA 1986 Regulated Under 268.32 Universal Treatment Standards (proposed) 0.054 mg/L Nap 40 CFR 268.48 EPA 1995b 60 FR 242 Guidelines: a. Air: ACGIH Ceiling Limit for Occupational Exposure 200 ppm (790 mg/m3) ACGIH 1994 (TLV-TWA) (CAS No. 540-59-0) NIOSH Recommended Exposure Limit for 200 ppm (790 mg/m3) NIOSH 1992 Occupational exposure (TWA) TWA (CAS No. 540-59-0) b. Water: EPA 1-d Health Advisory 20 mg/L 4 mg/L EPA 1995¢ (child) (child) 10-d Health Advisory 2 mg/L 3 mg/L EPA 1995¢ (child) (child) Lifetime Health Advisory 0.1 mg/L 0.07 mg/L EPA 1995¢c (adult) (adult) Longer-term Health Advisory 6 mg/L 11 mg/L EPA 1995¢ (adult) (adult) 2 mg/L 3 mg/L (child) (child) Maximum Contaminant Level 0.1 mg/L 0.07 mg/L EPA 1995¢ Maximum Contaminant Level Guideline 0.1 mg/L 0.07 mg/L EPA 1995¢ c. Other: EPA Cancer classification None Df IRIS 1995 NTP Cancer classification None None 1,2-DICHLOROETHENE 129 7. REGULATIONS AND ADVISORIES Table 7-1. Regulations and Guidelines Applicable to trans- and cis-1,2-Dichloroethene (continued) Agency Description Information Reference trans cis STATE Regulations and Guidelines a. Air: Acceptable Ambient Air Concentration NATICH 1992 Guidelines or Standards® AZ 1 hr avg. time 238x104 pg/m® (6.00 ppm) 24 hr avg. time 6.30x10*3 pg/m® (1.60 ppm) CT 8 hr avg. time 1.58x10%4 pg/m® (3.99 ppm) FL-PINELLA 8 hr avg. time 2.90x10*3 pg/m® (0.731 ppm) 24 hr avg. time 6.96x10+2 ug/m® (0.176 ppm) MA 24 hr avg. time 2.16x10+2 pg/m® (0.054 ppm) Annual avg. time 1.08x10+2 pg/m® (0.027 ppm) ND 8 hr avg. time 7.93 mg/m3 (2.00 ppm) NV 8 hr avg. time 1.88x10+! mg/m® (4.74 ppm) NY Annual avg. Time 3.6x10° 1.9x10% Sittig 1994 pg/m3 g/m? (0.091 ppm) (0.479 ppm) OK 24 hr avg. time 7.93x10%4 NATICH 1992 pg/m® (20.00 ppm) 1p 30 min avg. time 7.93x10+3 pg/m® (2.00 ppm) 1,2-DICHLOROETHENE 130 7. REGULATIONS AND ADVISORIES Table 7-1. Regulations and Guidelines Applicable to trans- and cis-1,2-Dichloroethene (continued) Agency Description Information Reference trans cis STATE (Cont.) Annual avg. time 7.90x10*2 pg/m3 (0.199 ppm) 30 min avg. time 7.90x10*3 pg/m® (2.00 ppm) Annual avg. time 7.90x10*2 ug/m® (0.199 ppm) VA 24 hr avg. time 1.30x10*4 pg/m® (3.28 ppm) vT 8 hr avg. time 7.90x10*4 pg/m® (19.93 ppm) WA-SWEST 24 hr avg. time 2.63x10*3 ug/m® (0.663 ppm) b. Water: Water Quality: Human Health CELDs 1993 AZ Domestic water source 100 ug/L 70 ug/L Fish consumption 13,000 ug/L CA Drinking water guideline 10 ug/L 6 ug/L FSTRAC 1990 CT Listed but no values CELDs 1993 DE Freshwater fish ingestion only 130.0 mg/L Freshwater fish & water ingestion 700 ug/L Marine, estuarine fish/shellfish 19.0 mg/L ingestion . FL Domestic/Drinking water 100 ug/L 70 ug/L Sittig 1994 KS Drinking water guideline 70 ug/L 70 ug/L FSTRAC 1990 MA Drinking water guideline 70 ug/L 70 ug/L ME Drinking water guideline 70 ug/L 70 ug/L Mi Domestic/Drinking water 120 ug/L 77 ug/L Sittig 1994 MN Drinking water guideline 70 ug/L 70 ug/L FSTRAC 1990 1,2-DICHLOROETHENE 131 7. REGULATIONS AND ADVISORIES Table 7-1. Regulations and Guidelines Applicable to trans- and cis-1,2-Dichloroethene (continued) Agency Description Information Reference trans cis STATE (Cont) MO Fish consumption 140,000 CELDs 1993 Hg/L Drinking water supply 700 pg/L NH Drinking water guideline 100 ug/L 70 ug/L FSTRAC 1990 NJ Drinking water standard: generic 100 ug/L 10 ug/L Sittig 1994 NY Domestic/Drinking water 5 pg/L OR Generic: Water & fish ingestion 0.033 ug/L CELDs 1993 Domestic/Drinking water 100 ug/L 70 ug/L Sittig 1994 Fish consumption only 1.85 ug/L CELDs 1993 RI Drinking water guideline 70 ug/L FSTRAC 1990 TN Domestic/Drinking water 100 ug/L 70 ug/L Sittig 1994 TX Domestic/Drinking water 70 ug/L vT Drinking water guideline: generic 70 ug/L FSTRAC 1990 wi Drinking water guideline 100 ug/L 100 ug/L Water Quality: Aquatic CELDs 1993 AL Listed but no value AZ Acute-cold water fishery 68,000 ug/L Acute-warm water fishery 68,000 ug/L Acute-effluent dominated water 68,000 ug/L Chronic-cold water fishery 3,900 ug/L Chronic-warm water fishery 3,900 ug/L Chronic-effluent dominated water 3,900 ug/L NJ Generic "Dichloroethylenes” (1,2 11,600 dce listed as subset but no value) - Acute-freshwater (max) Acute-saltwater (max) 224,000 OH Exceptional modified, & seasonal 7000 ug/L warm water; outside mixing zone; ‘ max Exceptional modified, & seasonal 310 ug/L warm water; outside mixing zone; max; 30-d avg. Exceptional modified, & seasonal 14,000 ug/L warm water; outside mixing zone; inside mixing zone; maximum 1,2-DICHLOROETHENE 132 7. REGULATIONS AND ADVISORIES Table 7-1. Regulations and Guidelines Applicable to trans- and cis-1,2-Dichloroethene (continued) Agency Description Information Reference trans cis STATE (Cont.) Cold water & limited resource 7,000 ug/L warmwater; outside mixing zone; maximum Coldwater & limited resource 310 ug/L warmwater; 30-d avg. Cold water & limited resource 14,000 ug/L warmwater; inside mixing zone; max OR Generic: Acute-freshwater 11,600 ug/L Acute-marine 224,000ug/L Water Quality: Recreational Use CELDs 1993 AZ Full body contact 2,800 ug/L Partial body contact 2,800 ug/L Groundwater Quality Standards CELDs 1993 MO 700 ug/L NC Class GS 0.07 mg/L Class GS 0.07 mg/L wi Enforcement standard 100 ug/L Preventive action limit 10 ug/L Enforcement standard 100 ug/L Preventive action limit 20 ug/L Groundwater Monitoring Parameter CELDs 1993 co Generic Yes IL Yes LA Yes MN Yes VA Yes Wi Yes MCLG'’s = MCLs or Action Levels Wi 0.1 mg/L 0.07 mg/L SD Surfacewater Discharge Permit Application Yes Requirements: Testing Requirements for Organic Toxic Pollutants NJ NPDES Permits: Testing Requirements for Yes Organic Toxic Pollutants 1,2-DICHLOROETHENE 133 7. REGULATIONS AND ADVISORIES Table 7-1. Regulations and Guidelines Applicable to trans- and cis-1,2-Dichloroethene (continued) Agency Description Information Reference trans cis STATE (Cont.) WI Toxic Discharge Yes c. Other: Hazardous Waste CELDs 1993 co Yes (LDR) IL Yes Generic Yes LA Yes MA Yes (LDR) Hazardous Waste Constituents CELDs 1993 CO Yes IL Yes LA Yes Generic Yes Generic Yes MN Generic Yes ND Generic Yes wv Generic Yes (App. Vill) wi Generic Yes (App. IV) NOTE: Update of drinking water guidelines and other areas in progress. Units in table reflect values and units of measure designated by each agency in its regulations or advisories. 2 Not classifiable as to human carcinogenicity b additional Guidelines or Standards for a mixture of cis- and trans-1,2-dichloroethene (CAS No. 540-59-0) ACGIH = American Conference of Governmental and Industrial Hygienists; CAS = Chemical Abstracts Services; CELDs = Computer-aided Environmental Legislative Database; CFR = Code of Federal Regulations; CPSC = Consumer Product Safety Commission; EPA = Environmental Protection Agency; FR = Federal Register; FSTRAC = Federal State Toxicology and Regulatory Alliance Committee; GC/MS = Gas Chromatography/Mass Spectrometry; IARC = International Agency for Research on Cancer; IRIS = Integrated Risk Information System; LDR = Land Disposal Restrictions; MCL = Maximum Contaminant Level; MCLG = Maximum Contaminant Level Goal; NA = Not available at the present time; NAp = Not applicable; NATICH = National Air Toxics Information Clearinghouse; NIOSH = National Institute of Occupational Safety and Health; NPDES = National Pollutant Discharge Elimination System; ODW = Office of Drinking Water ;OERR = Office of Emergency and Remedial Response; OSW = Office of Solid Waste; OW = Office of Water; TLV = Threshold Limit Value; TWA = Time Weighted Average; WHO = World Health Organization 1,2-DICHLOROETHENE 135 8. 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TOMES (Toxicology, Occupational Medicine and Environment Series), electronic data base Vol 78, Micromedex, Inc. *TRI91. 1993. Toxic Chemical Release Inventory. National Library of Medicine, National Toxicology Information Program, Bethesda, MD. 1,2-DICHLOROETHENE 154 8. REFERENCES *TRI93. 1995. Toxic Chemical Release Inventory. National Library of Medicine, National Toxicology Information Program, Bethesda, MD. *Tuazon EC, Atkinson R, Aschmann SM, et al. 1988. Atmospheric reactions of chloroethenes with the OH radical. International Journal of Chemical Kinetics. 20:241-265. *Tuazon EC, Atkinson R, Winer AM, et al. 1984. A study of the atmospheric reaction of 1,3 dichloropropene and other selected organochlorine compounds. Arch Environ Contam Toxicol 13:691-700. *Uehori R, Nagata T, Kimura K, et al. 1987. Screening of volatile compounds present in human blood using retention indices in gas chromatography. J Chrom 411:251-257. *Van H. 1988. OPD chemical buyers directory. 76th ed. New York, NY: Shnell Publishing Co., 239. *Vannelli T, Logan M, Arciero DM, et al. 1990. Degradation of halogenated aliphatic compounds by the ammonia-oxidizing bacterium Nitrosomonas europaea. Appl Env Micro 56(4):1169-1171. *Veith GD, Kosian P. 1983. Estimating bioconcentration potential from octanol/water partition coefficients. In: MacKay, et al. eds. Physical behavior of PCBs in the Great Lakes. Ann Arbor, MI: Ann Arbor Science Publishers, 269-282. *VIAR. 1987. Contract laboratory statistical database. Output Date: April 13, 1987. VIEW Database. 1989. Agency for Toxic Substances and Disease Registry (ATSDR), Office of External Affairs, Exposure and Disease Registry Branch, Atlanta, GA. November 8, 1989. Villalobos R, Annino R. 1991. Computer-aided design and optimization of an on-line gas chromatographic procedure for the analysis of purgeable compounds in waste water. J High Res Chrom 14:681-685. *Vogel TM, Criddle CS, McCarty PL. 1987. Transformations of halogenated aliphatic compounds. Environ Sci Technol 2(8):722-736. *Vogt WG, Walsh JJ. 1985. Volatile organic compounds in gases from landfill simulators. In: Proc Apca Annu Meet 78:17. *Wang T, Lenahan R, Kanik M. 1985b. Impact of trichloroethylene contaminated groundwater discharged to the main canal and Indian River Lagoon. Vero Beach, Florida. Bull Environ Contam Toxicol 34:578-586. *Wang T, Lenahan R, Kanik M, et al. 1985a. The removal of trichloroethylene contaminated groundwater at Vero Beach, Florida. Arch Environ Contam Toxicol 14:719-723. Ware GW ed. 1988. Cis and trans-1,2-dichloroethylene. In: Reviews of Environmental Contamination and Toxicology. U.S. Environmental Protection Agency, Office of Drinking Water, Health Advisories 106:93-112. 1,2-DICHLOROETHENE 155 8. REFERENCES *Weast RC. 1983. CRC handbook of chemistry and physics. 72nd ed. Boca Raton, FL: CRC Press, Inc., C295. *Westrick JJ, Mello JW, Thomas RF. 1984. The groundwater supply survey. J Amer Water Works Assoc 76:52-59. Williams DT, Coburn JA, Bancsi JJ. 1984. Study of total organic halogen as a means to detect groundwater contamination. Environ Int 10:39-44. *Wilson BH, Smith GB, Rees JF. 1986. Biotransformations of selected alkylbenzenes and halogenated aliphatic hydrocarbons in methanogenic aquifer material: A microcosm study. Environ Sci Technol 20:997-1002. *Winer AM, Atkinson R. 1987. Lifetimes and fates of toxic chemicals in California's atmosphere. Riverside, CA: California University. *Witmer C, Cooper K, Jowa L, et al. 1990. Oral toxicity of trans-1,2-dichloroethylene (DCE) and 1,1,1-trichloroethane (TCE) given alone and in combination to rats [Abstract]. Toxicologist 10:51. *Wolf F, Gorelik L. 1984. Persistence of synthetic solvent contaminants in a glacial outwash. Aquifer, Washington State. Munic Ind Waste, 7th Annu Madison Waste Conf, 116-131. *Wood JA, Porter ML. 1987. Hazardous pollutants in class II landfills. J Air Pollut Control Assoc 37:609-615. *Wylie PL. 1988. Comparing headspace with purge and trap for analysis of volatile priority pollutants. J Am Water Works Assoc 80:65-72. *Yeh and Kastenberg. 1991. Health risk assessment of biodegradable volatile organic chemicals: a case study of PCE, TCE, DCE, and VC. Journal of Hazardous Materials. 27:111-126. *Zhang Z. 1991. A gas-phase reactivity study of OH radicals with 1,1-dichloroethene and cis- and trans-1,2-dichloroethene over the temperature range 240-400° K. J Phys Chem 95:194-196. 1,2-DICHLOROETHENE 157 9. GLOSSARY Acute Exposure -- Exposure to a chemical for a duration of 14 days or less, as specified in the Toxicological Profiles. Adsorption Coefficient (K,.) -- The ratio of the amount of a chemical adsorbed per unit weight of organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. Adsorption Ratio (Kd) -- The amount of a chemical adsorbed by a sediment or soil (i.e., the solid phase) divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or sediment. Bioconcentration Factor (BCF) -- The quotient of the concentration of a chemical in aquatic organisms at a specific time or during a discrete time period of exposure divided by the concentration in the surrounding water at the same time or during the same period. Cancer Effect Level (CEL) -- The lowest dose of chemical in a study, or group of studies, that produces significant increases in the incidence of cancer (or tumors) between the exposed population and its appropriate control. Carcinogen -- A chemical capable of inducing cancer. Ceiling Value -- A concentration of a substance that should not be exceeded, even instantaneously. Chronic Exposure -- Exposure to a chemical for 365 days or more, as specified in the Toxicological Profiles. Developmental Toxicity -- The occurrence of adverse effects on the developing organism that may result from exposure to a chemical prior to conception (either parent), during prenatal development, or postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point in the life span of the organism. Embryotoxicity and Fetotoxicity -- Any toxic effect on the conceptus as a result of prenatal exposure to a chemical; the distinguishing feature between the two terms is the stage of development during which the insult occurred. The terms, as used here, include malformations and variations, altered growth, and in utero death. EPA Health Advisory -- An estimate of acceptable drinking water levels for a chemical substance based on health effects information. A health advisory is not a legally enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. Immediately Dangerous to Life or Health (IDLH) -- The maximum environmental concentration of a contaminant from which one could escape within 30 min without any escape-impairing symptoms or irreversible health effects. Intermediate Exposure -- Exposure to a chemical for a duration of 15-364 days, as specified in the Toxicological Profiles. 1,2-DICHLOROETHENE 158 9. GLOSSARY Immunologic Toxicity -- The occurrence of adverse effects on the immune system that may result from exposure to environmental agents such as chemicals. In Vitro -- Isolated from the living organism and artificially maintained, as in a test tube. In Vivo -- Occurring within the living organism. Lethal Concentration LO) (LCyLo) -- The lowest concentration of a chemical in air which has been reported to have cause Dn in humans or animals. Lethal Concentration sg, (LCs) -- A calculated concentration of a chemical in air to which exposure for a specific length of time is expected to cause death in 50% of a defined experimental animal population. Lethal Dosey (LD) -- The lowest dose of a chemical introduced by a route other than inhalation that is expected to have caused death in humans or animals. Lethal Doses) (LDgg) -- The dose of a chemical which has been calculated to cause death in 50% of a defined experimental animal population. Lethal Time 5, (LT5g) -- A calculated period of time within which a specific concentration of a chemical is expected to cause death in 50% of a defined experimental animal population. Lowest-Observed-Adverse-Effect Level (LOAEL) -- The lowest dose of chemical in a study, or group of studies, that produces statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control. Malformations -- Permanent structural changes that may adversely affect survival, development, or function. Minimal Risk Level -- An estimate of daily human exposure to a dose of a chemical that is likely to be without an appreciable risk of adverse noncancerous effects over a specified duration of exposure. Mutagen -- A substance that causes mutations. A mutation is a change in the genetic material in a body cell. Mutations can lead to birth defects, miscarriages, or cancer. Neurotoxicity -- The occurrence of adverse effects on the nervous system following exposure to chemical. No-Observed-Adverse-Effect Level (NOAEL) -- The dose of chemical at which there were no statistically or biologically significant increases in frequency or severity of adverse effects seen between the exposed population and its appropriate control. Effects may be produced at this dose, but they are not considered to be adverse. Octanol-Water Partition Coefficient (K,) -- The equilibrium ratio of the concentrations of a chemical in n-octanol and water, in dilute solution. Permissible Exposure Limit (PEL) -- An allowable exposure level in workplace air averaged over an 8-hour shift. 1,2-DICHLOROETHENE 159 9. GLOSSARY q;* -- The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the multistage procedure. The q;* can be used to calculate an estimate of carcinogenic potency, the incremental excess cancer risk per unit of exposure (usually pg/L for water, mg/kg/day for food, and ng/m> for air). Reference Dose (RfD) -- An estimate (with uncertainty spanning perhaps an order of magnitude) of the daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious effects during a lifetime. The RfD is operationally derived from the NOAEL (from animal and human studies) by a consistent application of uncertainty factors that reflect various types of data used to estimate RfDs and an additional modifying factor, which is based on a professional judgment of the entire database on the chemical. The RfDs are not applicable to nonthreshold effects such as cancer. Reportable Quantity (RQ) -- The quantity of a hazardous substance that is considered reportable under CERCLA. Reportable quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation either under CERCLA or under Sect. 311 of the Clean Water Act. Quantities are measured over a 24-hour period. Reproductive Toxicity -- The occurrence of adverse effects on the reproductive system that may result from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of this system. Short-Term Exposure Limit (STEL) -- The maximum concentration to which workers can be exposed for up to 15 min continually. No more than four excursions are allowed per day, and there must be at least 60 min between exposure periods. The daily TLV-TWA may not be exceeded. Target Organ Toxicity -- This term covers a broad range of adverse effects on target organs or physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited exposure to those assumed over a lifetime of exposure to a chemical. Teratogen -- A chemical that causes structural defects that affect the development of an organism. Threshold Limit Value (TLV) -- A concentration of a substance to which most workers can be exposed without adverse effect. The TLV may be expressed as a TWA, as a STEL, or as a CL. Time-Weighted Average (TWA) -- An allowable exposure concentration averaged over a normal 8-hour workday or 40-hour workweek. Toxic Dose (TDg) -- A calculated dose of a chemical, introduced by a route other than inhalation, which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. Uncertainty Factor (UF) -- A factor used in operationally deriving the RfD from experimental data. UFs are intended to account for (1) the variation in sensitivity among the members of the human population, (2) the uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using LOAEL data rather than NOAEL data. Usually each of these factors is set equal to 10. 1,2-DICHLOROETHENE A-1 APPENDIX A ATSDR MINIMAL RISK LEVEL The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99-499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological profiles for each substance included on the priority list of hazardous substances; and assure the initiation of a research program to fill identified data needs associated with the substances. The toxicological profiles include an examination, summary, and interpretation of available toxicological information and epidemiologic evaluations of a hazardous substance. During the development of toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are used by ATSDR health assessors to identify contaminants and potential health effects that may be of concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or action levels. MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will occur. 1,2-DICHLOROETHENE A-2 APPENDIX A MRLs are intended only to serve as a screening tool to help public health professionals decide where to look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health principle of prevention. Although human data are preferred, MRLs often must be based on animal studies because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes that humans are more sensitive to the effects of hazardous substance than animals and that certain persons may be particularly sensitive. Thus, the resulting MRL may be as much as a hundredfold below levels that have been shown to be nontoxic in laboratory animals. Proposed MRLs undergo a rigorous review process: Health EffectssMRL Workgroup reviews within the Division of Toxicology, expert panel peer reviews, and agencywide MRL Workgroup reviews, with participation from other federal agencies and comments from the public. They are subject to change as new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs in the most recent toxicological profiles supersede previously published levels. For additional information regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road, Mailstop E-29, Atlanta, Georgia 30333. 1,2-DICHLOROETHENE A-3 MINIMAL RISK LEVEL (MRL) WORKSHEET Chemical name: trans-1,2-dichloroethene CAS number: 156-60-5 Date: August 1996 Profile status: Final Route: [x] Inhalation [ ] Oral Duration: [x] Acute [ JIntermediate [ ] Chronic Key to figure: 2 Species: Rat MRL: 0.2 [ ] mg/kg/day [x] ppm [] mg/m’ Reference: Freundt, KJ, Liebaldt, GP, and Lieberwirth, E. 1977. Toxicity Studies on Trans-1,2-Dichloroethylene. Toxicology, 7, pp. 141-153. Experimental design Female, mature SPF Wistar Rats; 180-200 g. Exposure for 8 hours; 0, 200, 1,000, and 3,000 ppm of trans-1,2-dichloroethene by inhalation. 6 rats/group. Animals were sacrificed immediately following exposure and examined for gross pathology including lung, heart, liver, kidney, spleen, brain, quadriceps muscle and sciatic nerve. Standard hematological tests, clinical chemistry tests, and tests of clearance of bromosulphthalein in bile were carried out. ted in d i 0 e Slight to severe fatty degeneration of the hepatic lobules and Kupffer cells was seen in all dosing groups (except controls). At 200 ppm fatty degeneration and fatty accumulation in Kupffer cells was seen in 1/6 rats; at 1,000 and 3,000 ppm 1 or 2/6 rats showed similar liver and Kupffer cell changes. e Slight increases in capillary hyperaemia and alveolar septum distention were noted. ® Fibrous swelling, hyperemia and modified muscular striation were found in the cardiac muscles at 3,000 ppm in 2/6 rats. ® No pathological changes were seen in the kidneys, spleen, brain, or peripheral nerves. No central nervous system depression was seen. Dose endpoint used for MRL derivation: Fatty degeneration of liver cells: LOAEL = 200 ppm [1 NOAEL [x] LOAEL 1,2-DICHLOROETHENE A-4 APPENDIX A Uncertainty factors used in MRL derivation: [11 [13 [x] 10 (for use of a LOAEL) [11 [13 [x] 10 (for extrapolation from animals to humans) [11 [13 [x] 10 (for human variability) Was a conversion factor used from ppm in food or water to a mg/body weight dose? No. If so, explain: If an inhalation study in animals, list conversion factors used in determining human equivalent dose: The NOAEL (HEC) Was calculated for a gas:extrarespiratory effect in rats assuming periodicity was attained, using the following equation: NOAEL HEC) = NOAEL ii) x A 5/Ay;, where: NOAEL HEC) = the NOAEL human equivalent concentration; NOAEL (adj) = the NOAEL adjusted for continuous exposure (e.g., adjusted for exposure regimen by h hours/24 hours and d days/7 days); A,/Ay = the ratio of the blood to air partition coefficient of the chemical for the animal species to the human value, used only if A, >A. For the situation in which A, >A}; and in the case where A values are unknown, the default value of A Ary = 1 is recommended. For 1,2-dichloroethene, An =9.58 and Ay = 6.04, therefore 'N >A; and a default value of 1 was used. Was a conversion used from intermittent to continuous exposure? No. If so, explain: Other additional studies or pertinent information that lend support to this MRL: McCauley et al. (1990), Barnes et al. (1985), and McMillan (1986) also reported hepatic effects, from oral exposure to cis- or trans-1,2-dichloroethene. Agency Contact (Chemical Manager): Carolyn Harper 1,2-DICHLOROETHENE A-5 APPENDIX A MINIMAL RISK LEVEL WORKSHEET Chemical name: trans-1,2-dichloroethene CAS number: 156-60-5 Date: August 1996 Profile status: Final Route: [x] Inhalation [ ] Oral Duration: [ 1 Acute [x] Intermediate [ ] Chronic Key to figure: 11 Species: Rat MRL: 0.2 [ ] mg/kg/day [x] ppm [] mg/m’ Reference: Freundt, KJ, Liebaldt, GP, and Lieberwirth, E. 1977. Toxicity Studies on Trans-1,2-Dichloroethylene. Toxicology, 7, pp. 141-153. Experimental design ® Female, mature SPF Wistar Rats; 180-200 g. e Exposure for 8-hour periods, 5 days per week, for either 8 or 16 weeks, at or 200 ppm of trans-1,2-dichloroethene by inhalation. ® 6 rats/group. ® Animals were sacrificed immediately following exposure and examined for gross pathology including lung, heart, liver, kidney, spleen, brain, quadriceps muscle and sciatic nerve. Effects noted in study and corresponding doses: ® In the 8-week experiment, slight fatty degeneration of the hepatic lobules was observed in 3/6 exposed rats and severe fatty accumulation in the Kupffer cells was seen in 3/6 exposed rats (200 ppm). In the 16-week experiment, slight (2/6 exposed) and severe (3/6 exposed) fatty accumulation in the liver lobule was seen and slight fatty accumulation in the Kupffer cells was seen in 5/6 exposed rats (200 ppm). e Slight increases in capillary hyperaemia and alveolar septum distention were seen. ® No pathological changes were seen in the kidneys, spleen, brain, striated muscle, or peripheral nerves. No central nervous system depression was seen. Dose endpoint used for MRL derivation: Fatty degeneration of liver cells: LOAEL = 200 ppm [ 1 NOAEL [x] LOAEL Uncertainty factors used in MRL derivation: [11 [13 [x] 10 (for use of a LOAEL) [11 [13 [x] 10 (for extrapolation from animals to humans) [11 [13 [x] 10 (for human variability) 1,2-DICHLOROETHENE A-6 APPENDIX A If an inhalation study in animals, list conversion factors used in determining human equivalent dose: The NOAEL (HEC) Was calculated for a gas:extrarespiratory effect in rats assuming periodicity was attained, using the following equation: NOAEL mec) = NOAEL (4 x A, /Ay, where: NOAEL HEC) = the NOAEL human equivalent concentration; NOAEL , dj) = the NOAEL adjusted for continuous exposure (e.g., adjusted for exposure regimen by h hours/24 hours and d days/7 days); A p/Ay = the ratio of the blood to air partition coefficient of the chemical for the animal species to the human value, used only if Ap >A. For the situation in which A, >A}; and in the case where A values are unknown, the default value 4) Vy, = 1 is recommended. For 1 2 dichloroethene, A, = 9.58 and A; = 6.04, therefore A, >A; and a default value of 1 was used. Was a conversion used from intermittent to continuous exposure? No. If so, explain: Other additional studies or pertinent information that lend support to this MRL: McCauley et al. (1990), Barnes et al. (1985), and McMillan (1986) also reported hepatic effects, from oral exposure to cis- or trans-1,2-dichloroethene. Agency Contact (Chemical Manager): Carolyn Harper 1,2-DICHLOROETHENE A-7 APPENDIX A MINIMAL RISK LEVEL WORKSHEET Chemical name: cis-1,2-dichloroethene CAS number: 156-60-5 Date: August 28, 1996 Profile status: Final Route: [ ] Inhalation [x ]Oral Duration: [x ] Acute [ Intermediate [ ] Chronic Key to figure: 8 Species: rat MRL: 1 [x] mg/kg/day []ppm [] mg/m’ Reference: McCauley et al. 1990. The effects of subacute and subchronic oral exposure to cis-1,2-dichloroethylene in rats. Health Effects Research Laboratory, U.S. EPA, Cincinnati, OH and Air Force Aerospace Medical Research Laboratory, Wright-Patterson AFB, OH. Experimental design : Male and female Sprague-Dawley-derived Charles River rats. Doses: 1.0, 3.0, 10.0, 20.0 mM/kg/day (97, 290, 970, 1,900 mg/kg/day) Administration was in corn oil via gavage for 14 days. 10 rats/sex/group. Food and water were available ad libitum, body weights were taken weekly. At the end of the exposure period, all animals were sacrificed and specimens were collected for clinical chemistry, hematology, and histopathology studies. Effects noted in study and corresponding doses: Mortality was observed in rats treated with 970 mg/kg/day (2/20) and 1,900 mg/kg/day (5/20). CNS depression was observed at 1,900 mg/kg/day. Increased absolute and relative liver weights in treated males and female rats at 97 mg/kg/day. Increased absolute and relative kidney weights in females at doses greater than or equal to 970 mg/kg/day. Decreased blood urea nitrogen at 290 mg/kg/day and increased serum cholesterol in females at 1,900 mg/kg/day. ® Decreased hematocrit levels and erythrocyte counts in females at doses greater than or equal to 290 mg/kg/day. ® Increased serum calcium levels in males at doses greater or equal to 970 mg/kg/day. Dose endpoint used for MRL derivation: Decreased hematocrit in females NOAEL = 97 mg/kg/day. [x 1 NOAEL [ JLOAEL 1,2-DICHLOROETHENE A-8 APPENDIX A ncertainty f i ivation: [11 [13 []10 (for use of a LOAEL) [11 [13 [x] 10 (for extrapolation from animals to humans) [11 [13 [x] 10 (for human variability) Was a conversion factor used from ppm in food or water to a mg/body weight dose? If so, explain: No If an inhalati i i i i d in determining human equivalent dose: If so, explain: No ther addition i i i i n rt to this MRL: Hematological effects have also been noted in other oral studies. Barnes et al. (1985) reported a 12% decrease in fibrinogen levels and a 7% decrease in prothrombin time in mice exposed to 210 mg/kg/day trans-1,2-dichloroethene. Agency Contact (Chemical Manager): Carolyn Harper 1,2-DICHLOROETHENE A-9 APPENDIX A MINIMAL RISK LEVEL WORKSHEET Chemical name: cis-1,2-dichloroethene CAS number: 156-60-5 Date: August 28, 1996 Profile status: Final Route: [ ] Inhalation [x ]Oral Duration: [ 1 Acute [x ]Intermediate [ ] Chronic Key to figure: 15 Species: rat MRL: 0.3 [x ] mg/kg/day []ppm [] mg/m Reference: McCauley et al. 1990. The effects of subacute and subchronic oral exposure to cis-1,2-dichloroethylene in rats. Health Effects Research Laboratory, U.S. EPA, Cincinnati, OH and Air Force Aerospace Medical Research Laboratory, Wright-Patterson AFB, OH. Experimental design: Male and female Sprague-Dawley-derived Charles River rats. Doses: 0.33, 1.0, 3.0, and 9.0 mM/kg/day (32, 97, 290, 870 mg/kg/day) Administration was in corn oil via gavage for 90 days. 10 rats/sex/group. Food and water were available ad libitum, body weights were taken weekly. At the end of the exposure period, all animals were sacrificed and specimens were collected for clinical chemistry, hematology, and histopathology studies. Effects noted in study and corresponding doses: ® Mortality was observed in the control group and all four treatment groups within the first week: 1/20, 1/20, 1/20, 3/20, 4/20 respectively. ® Increased relative kidney weight in male rats at 870 mg/kg/day and increased relative liver weights in male and female rats given greater than or equal to 97 mg/kg/day were observed. ® Increased relative thymus weights were observed in females treated at 870 mg/kg/day. ® A dose related decrease in blood urea nitrogen and serum creatinine was observed at 870 mg/kg/day. ® Decreased hematocrit levels in males at doses greater than or equal to 97 mg/kg/day and in females at doses greater than or equal to 290 mg/kg/day was observed. ® Decreased hemoglobin levels in males at doses greater than or equal to 290 mg/kg/day and in females at 290 mg/kg/day was noted. ® A 27% decrease in body weight was observed in males at 290 mg/kg/day and a 10% decrease in body weight was observed in males at 97 mg/kg/day. 1,2-DICHLOROETHENE A-10 APPENDIX A Dose endpoint used for MRL derivation: Decreased hematocrit and hemoglobin: NOAEL = 32 mg/kg/day. [x I NOAEL [ JLOAEL Uncertainty factors used in MRL derivation: [11 [13 []10 (for use of a LOAEL) [11 [13 [x]10 (for extrapolation from animals to humans) [11 []3 [x]10 (for human variability) Was a conversion factor used from ppm in food or water to a mg/body weight dose? If so, explain: No If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Was a conversion used from intermittent to continuous exposure? If so, explain: No ther additional studies or pertinent in ation that lend su his MRL: Hematological effects have also been noted in other oral studies. Barnes et al. (1985) reported a 12% decrease in fibrinogen levels and a 7% decrease in prothrombin time in mice exposed to 210 mg/kg/day trans-1,2-dichloroethene. Agency Contact (Chemical Manager): Carolyn Harper 1,2-DICHLOROETHENE A-11 APPENDIX A MINIMAL RISK LEVEL WORKSHEET Chemical name: trans-1,2-dichloroethene CAS number: 156-60-5 Date: August 28, 1996 Profile status: Final Route: [ ] Inhalation [x] Oral Duration: [ ] Acute [x] Intermediate [ ] Chronic Key to figure: 17 Species: Mouse MRL: 0.2 [x] mg/kg/day []ppm [] mg/m’ Reference: Barnes DW, Sanders VM, White KL Jr, Shopp GM, and Munson AE. 1985. Toxicology of trans-1,2-Dichloroethylene in the Mouse. Drug and Chemical Toxicology 8(5):373-392. Experimental design: ® 90-day study with 260 male and 260 female mice in the control group and 140 mice of each sex in groups exposed to drinking water with 0.1, 1.0, or 2.0 mg trans-1,2-dichlorethene/mL (males: 0, 17, 175, 387 mg/kg/day; females: 0, 23, 224, 452 mg/kg/day). e Exposure was averaged over the 90 days. ® Trans-1,2-dichloroethene was maintained in solution using a 1% emulphor (vegetable oil) and deionized water. Effects noted in study and corresponding doses: ® No trans-1,2-dichloroethene-induced changes in terminal body weight or gross pathology. ® Male mice showed an increase in relative liver weights (8%) and increased serum alkaline phosphatase at 175 mg/kg/day. e Glucose levels were elevated in all exposure groups for both sexes and males showed decreased glutathione levels at 387 mg/kg/day. ® An 11% decrease in relative lung weight was seen in female mice at 452 mg/kg/day. e No effects were noted on hematocrit, hemoglobin, or erythrocyte and platelet counts. Dose endpoint used for MRL derivation: Increased serum alkaline phosphatase NOAEL = 17 mg/kg/day [x] NOAEL [ ]LOAEL 1,2-DICHLOROETHENE A-12 APPENDIX A Uncertainty factors used in MRL derivation: [11 [13 []10 (for use of a LOAEL) [11 [13 [x] 10 (for extrapolation from animals to humans) [11 [13 [x] 10 (for human variability) Was a conversion factor used from ppm in food or water to a mg/body weight dose? Author provided. If so, explain: If an inhalation study in animals, list conversion factors used in determining human equivalent dose: Was a conversion used from intermittent to continuous exposure? No. If so, explain: Other additional studies or pertinent information that lend support to this MRL: McCauley et al. (1990) and McMillan (1986) also reported hepatic effects from oral exposure to trans-1,2-dichloroethene. Agency Contact (Chemical Manager): Carolyn Harper 1,2-DICHLOROETHENE B-1 APPENDIX B USER'S GUIDE Chapter 1 Public Health Statement This chapter of the profile is a health effects summary written in non-technical language. Its intended audience is the general public especially people living in the vicinity of a hazardous waste site or chemical release. If the Public Health Statement were removed from the rest of the document, it would still communicate to the lay public essential information about the chemical. The major headings in the Public Health Statement are useful to find specific topics of concern. The topics are written in a question and answer format. The answer to each question includes a sentence that will direct the reader to chapters in the profile that will provide more information on the given topic. Chapter 2 Tables and Figures for Levels of Significant Exposure (LSE) Tables (2-1, 2-2, and 2-3) and figures (2-1 and 2-2) are used to summarize health effects and illustrate graphically levels of exposure associated with those effects. These levels cover health effects observed at increasing dose concentrations and durations, differences in response by species, minimal risk levels (MRLs) to humans for noncancer endpoints, and EPA's estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to locate data for a specific exposure scenario. The LSE tables and figures should always be used in conjunction with the text. All entries in these tables and figures represent studies that provide reliable, quantitative estimates of No-Observed-Adverse- Effect Levels (NOAELSs), Lowest-Observed-Adverse-Effect Levels (LOAELSs), or Cancer Effect Levels (CELs). The legends presented below demonstrate the application of these tables and figures. Representative examples of LSE Table 2-1 and Figure 2-1 are shown. The numbers in the left column of the legends correspond to the numbers in the example table and figure. LEGEND See LSE Table 2-1 (1) Route of Exposure One of the first considerations when reviewing the toxicity of a substance using these tables and figures should be the relevant and appropriate route of exposure. When sufficient data exists, three LSE tables and two LSE figures are presented in the document. The three LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, and dermal (LSE Table 2-1, 2-2, and 2-3, respectively). LSE figures are limited to the inhalation (LSE Figure 2-1) and oral (LSE Figure 2-2) routes. Not all substances will have data on each route of exposure and will not therefore have all five of the tables and figures. 1,2-DICHLOROETHENE B-2 (2) 3) 4) 5) (6) (7 (8) ©) APPENDIX B Exposure Period Three exposure periods - acute (less than 15 days), intermediate (15-364 days), and chronic (365 days or more) are presented within each relevant route of exposure. In this example, an inhalation study of intermediate exposure duration is reported. For quick reference to health effects occurring from a known length of exposure, locate the applicable exposure period within the LSE table and figure. Health Effect The major categories of health effects included in LSE tables and figures are death, systemic, immunological, neurological, developmental, reproductive, and cancer. NOAELs and LOAELSs can be reported in the tables and figures for all effects but cancer. Systemic effects are further defined in the "System" column of the LSE table (see key number 18). Key to Figure Each key number in the LSE table links study information to one or more data points using the same key number in the corresponding LSE figure. In this example, the study represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL (also see the 2 "18r" data points in Figure 2-1). Species The test species, whether animal or human, are identified in this column. Section 2.5, "Relevance to Public Health," covers the relevance of animal data to human toxicity and Section 2.3, "Toxicokinetics," contains any available information on comparative toxicokinetics. Although NOAELs and LOAELSs are species specific, the levels are extrapolated to equivalent human doses to derive an MRL. Exposure Frequency/Duration The duration of the study and the weekly and daily exposure regimen are provided in this column. This permits comparison of NOAELs and LOAELSs from different studies. In this case (key number 18), rats were exposed to toxaphene via inhalation for 6 hours per day, 5 days per week, for 3 weeks. For a more complete review of the dosing regimen refer to the appropriate sections of the text or the original reference paper, i.e., Nitschke et al. 1981. System This column further defines the systemic effects. These systems include: respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and dermal/ocular. "Other" refers to any systemic effect (e.g., a decrease in body weight) not covered in these systems. In the example of key number 18, 1 systemic effect (respiratory) was investigated. NOAEL A No-Observed-Adverse-Effect Level (NOAEL) is the highest exposure level at which no harmful effects were seen in the organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system which was used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see footnote "b"). LOAEL A Lowest-Observed-Adverse-Effect Level (LOAEL) is the lowest dose used in the study that caused a harmful health effect. LOAELSs have been classified into "Less Serious" and "Serious" effects. These distinctions help readers identify the levels of exposure at which adverse health effects first appear and the gradation of effects with increasing dose. A brief description of the specific endpoint used to quantify the adverse effect accompanies the LOAEL. The respiratory effect reported in key number 18 (hyperplasia) is a Less serious LOAEL of 10 ppm. MRLs are not derived from Serious LOAELSs. (10) Reference The complete reference citation is given in chapter 8 of the profile. 1,2-DICHLOROETHENE B-3 an) 12) APPENDIX B CEL A Cancer Effect Level (CEL) is the lowest exposure level associated with the onset of carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious effects. The LSE tables and figures do not contain NOAELSs for cancer, but the text may report doses not causing measurable cancer increases. Footnotes Explanations of abbreviations or reference notes for data in the LSE tables are found in the footnotes. Footnote "b" indicates the NOAEL of 3 ppm in key number 18 was used to derive an MRL of 0.005 ppm. LEGEND See Figure 2-1 LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the reader quickly compare health effects according to exposure concentrations for particular exposure periods. (13) (14) (15) (16) a7) (18) (19) Exposure Period The same exposure periods appear as in the LSE table. In this example, health effects observed within the intermediate and chronic exposure periods are illustrated. Health Effect These are the categories of health effects for which reliable quantitative data exists. The same health effects appear in the LSE table. Levels of Exposure concentrations or doses for each health effect in the LSE tables are graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log scale "y" axis. Inhalation exposure is reported in mg/m’ or pprh and oral exposure is reported in mg/kg/day. NOAEL In this example, 18r NOAEL is the critical endpoint for which an intermediate inhalation exposure MRL is based. As you can see from the LSE figure key, the open-circle symbol indicates to a NOAEL for the test species-rat. The key number 18 corresponds to the entry in the LSE table. The dashed descending arrow indicates the extrapolation from the exposure level of 3 ppm (see entry 18 in the Table) to the MRL of 0.005 ppm (see footnote "b" in the LSE table). CEL Key number 38r is 1 of 3 studies for which Cancer Effect Levels were derived. The diamond symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 corresponds to the entry in the LSE table. Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the upper-bound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived from the EPA's Human Health Assessment Group's upper-bound estimates of the slope of the cancer dose response curve at low dose levels (q;*). Key to LSE Figure The Key explains the abbreviations and symbols used in the figure. |- TABLE 2-1. Levels of Significant Exposure to [Chemical x] — Inhalation Exposure LOAEL (effect) Key to frequency/ NOAEL - : figure? Species duration ~~ System (ppm) Less serious (ppm) Serious (ppm) Reference INTERMEDIATE EXPOSURE a 1 l l l 18 Rat 13 wk Resp 3° 10 (hyperplasia) Nitschke et al. 5d/wk . 1981 6hr/d CHRONIC EXPOSURE Cancer 38 Rat 18 mo (CEL, multiple Wong et al. 1982 5d/wk organs) 7hr/d 39 Rat 89-104 wk 10 (CEL, lung tumors, NTP 1982 5d/wk nasal tumors) 6hr/d 40 Mouse 79-103 wk 10 (CEL, lung tumors, NTP 1982 5d/wk hemangiosarcomas) 6hr/d 2 The number corresponds to entries in Figure 2-1. b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5 x 1073 ppm; dose adjusted for intermittent exposure and divided by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 8 XION3ddv INIHLIOHOTHOIQ-2 + v-9 338 — > Figure 2-1. Levels of Significant Exposure to [Chemical X] - Inhalation Acute Intermediate (<14 days) (15-364 days) Systemic Systemic N N . & . id .Q@ S & SE ° © © 5 : Q & NE S S &@ eo? & & Cd & & RK RK > 0 r 18r 1 1 | 104 —, 1 0.1 10-5 | Estimated Y Upper Bound 0.01 ] Human Cancer Key 106 —{ Risk Levels 0.001 r Rat @ LOAEL for serious effects (animals) I Minimal risk level for effects 1077 1 m Mouse (PD LOAEL for less serious effects (animals) | oltier ian cancer 0.0001 h Rabbit (QO NOAEL (animals) g Guinea Pig CEL - Cancer Effect Level The number next to each point 0.00001 k Monkey * corresponds to entries in the accompanying table. 0.000001 Co } * Doses represent the lowest dose tested per study that produced a tumorigenic response and do not imply the existence of a threshold for the cancer end point. 0.0000001 8 XIAN3ddVY 3INIHLIOHOTHOIa-2'+ S-9 1,2-DICHLOROETHENE B-6 APPENDIX B Chapter 2 (Section 2.5) Relevance to Public Health The Relevance to Public Health section provides a health effects summary based on evaluations of existing toxicologic, epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weight-of-evidence discussions for human health endpoints by addressing the following questions. 1. What effects are known to occur in humans? 2. What effects observed in animals are likely to be of concern to humans? 3. What exposure conditions are likely to be of concern to humans, especially around hazardous waste sites? The section covers endpoints in the same order they appear within the Discussion of Health Effects by Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also considered in this section. If data are located in the scientific literature, a table of genotoxicity information is included. The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer endpoints (if derived) and the endpoints from which they were derived are indicated and discussed. Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public health are identified in the Data Needs section. Interpretation of Minimal Risk Levels Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not meant to support regulatory action; but to acquaint health professionals with exposure levels at which adverse health effects are not expected to occur in humans. They should help physicians and public health officials determine the safety of a community living near a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. MRLs are based largely on toxicological studies in animals and on reports of human occupational exposure. MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2.5, "Relevance to Public Health," contains basic information known about the substance. Other sections such as 2.7, "Interactions with Other Substances," and 2.8, "Populations that are Unusually Susceptible" provide important supplemental information. MRL users should also understand the MRL derivation methodology. MRLs are derived using a modified version of the risk assessment methodology the Environmental Protection Agency (EPA) provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 1,2-DICHLOROETHENE B-7 APPENDIX B To derive an MRL, ATSDR generally selects the most sensitive endpoint which, in its best judgement, represents the most sensitive human health effect for a given exposure route and duration. ATSDR cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available for all potential systemic, neurological, and developmental effects. If this information and reliable quantitative data on the chosen endpoint are available, ATSDR derives an MRL using the most sensitive species (when information from multiple species is available) with the highest NOAEL that does not exceed any adverse effect levels. When a NOAEL is not available, a lowest-observed- adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor (UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for human variability to protect sensitive subpopulations (people who are most susceptible to the health effects caused by the substance) and for interspecies variability (extrapolation from animals to humans). In deriving an MRL, these individual uncertainty factors are multiplied together. The product is then divided into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used in developing a substance-specific MRL are provided in the footnotes of the LSE Tables. 1,2-DICHLRORETHENE C-1 ACGIH ADME atm ATSDR BCF BSC C CDC CEL CERCLA CFR CLP cm CNS d DHEW DHHS DOL ECG EEG EPA EKG F Fy FAO FEMA FIFRA fpm ft FR g GC gen HPLC hr IDLH IARC ILO in Kd kg oC ow APPENDIX C ACRONYMS, ABBREVIATIONS, AND SYMBOLS American Conference of Governmental Industrial Hygienists Absorption, Distribution, Metabolism, and Excretion atmosphere Agency for Toxic Substances and Disease Registry bioconcentration factor Board of Scientific Counselors Centigrade Centers for Disease Control Cancer Effect Level Comprehensive Environmental Response, Compensation, and Liability Act Code of Federal Regulations Contract Laboratory Program centimeter central nervous system day Department of Health, Education, and Welfare Department of Health and Human Services Department of Labor electrocardiogram electroencephalogram Environmental Protection Agency see ECG Fahrenheit first filial generation Food and Agricultural Organization of the United Nations Federal Emergency Management Agency Federal Insecticide, Fungicide, and Rodenticide Act feet per minute foot Federal Register gram gas chromatography generation high-performance liquid chromatography hour Immediately Dangerous to Life and Health International Agency for Research on Cancer International Labor Organization inch adsorption ratio kilogram metric ton organic carbon partition coefficient octanol-water partition coefficient 1,2-DICHLRORETHENE L LC LC, LCs0 LD, LDsq LOAEL LSE m mg min mL mm mmHg mmol mo mppcf MRL MS NIEHS NIOSH NIOSHTIC ng nm NHANES nmol NOAEL NOES NOHS NPL NRC NTIS NTP OSHA PEL Pg pmol PHS PMR ppb ppm ppt REL RfD RTECS sec SCE SIC SMR APPENDIX C liter liquid chromatography lethal concentration, low lethal concentration, 50% kill lethal dose, low lethal dose, 50% kill lowest-observed-adverse-effect level Levels of Significant Exposure meter milligram minute milliliter millimeter millimeters of mercury millimole month millions of particles per cubic foot Minimal Risk Level mass spectrometry National Institute of Environmental Health Sciences National Institute for Occupational Safety and Health NIOSH's Computerized Information Retrieval System nanogram nanometer National Health and Nutrition Examination Survey nanomole no-observed-adverse-effect level National Occupational Exposure Survey National Occupational Hazard Survey National Priorities List National Research Council National Technical Information Service National Toxicology Program Occupational Safety and Health Administration permissible exposure limit picogram picomole Public Health Service proportionate mortality ratio parts per billion parts per million parts per trillion recommended exposure limit Reference Dose Registry of Toxic Effects of Chemical Substances second sister chromatid exchange Standard Industrial Classification standard mortality ratio 1,2-DICHLRORETHENE ROR KAA NIV YV by = % 5 APPENDIX C short term exposure limit STORAGE and RETRIEVAL threshold limit value Toxic Substances Control Act Toxics Release Inventory time-weighted average United States uncertainty factor year World Health Organization week greater than greater than or equal to equal to less than less than or equal to percent alpha beta delta gamma micron microgram o U.S. GOVERNMENT PRINTING OFFICE: 1996-739-324 C-3 E016 1,02 U.C. 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