TECHNICAL INFORMATION

Effects of Perchloroethylene / Drug
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Interaction on Foor b
Behavior and Neurological Function “’~”

U.S.DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE / _ Public Health Service
__ Center For Disease Control / National Institute For Occupational Safety And Health

 
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''EFFECTS OF PERCHLOROETHYLENE/DRUG INTERACTION ON
BEHAVIOR AND NEUROLOGICAL FUNCTION

Richard D. Stewart, M.D.
Carl L. Hake, Ph.D.
Anthony Wu, Ph.D.

John Kalbfleisch, Ph.D.
Paul E. Newton, M.S.
Sandra K. Marlow, M.S.
Miliana Vucicevic-Salama, M.D.

Department of Environmental Medicine
The Medical College of Wisconsin
Allen-Bradley Medical Science Laboratory
8700 West Wisconsin Avenue
Milwaukee, Wisconsin 53226

Final Report
Contract No. CDC 201-75-0059

With Addendum by
Vernon R. Putz, Ph.D.
Behavioral and Motivational Factors Branch
NIOSH

U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE
Public Health Service
Center for Disease Control
National Institute for Occupational Safety and Health
Division of Biomedical and Behavioral Science
4676 Columbia Parkway
Cincinnati, Ohio 45226
April 1977

 

For sale by the Superintendent of Documents, U.S. Government
Printing Office, Washington, D.C. 20402
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DISCLAIMER

The contents of this report are reproduced herein
as received from the contractor.

The opinions, findings, and conclusions expressed
herein are not necessarily those of the National
Institute for Occupational Safety and Health, nor
does mention of company names or products consti-
tute endorsement by the National Institute for Oc-
cupational Safety and Health.

NIOSH Project Officers
Charles Xintaras and Vernon R. Putz

DHEW (NIOSH) Publication No. 77-191

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ABSTRACT HEALT

Perchloroethylene (PCE, tetrachloroethylene) vapor is commonly found in
the workers’ environment in dry cleaning establishments and industrial
degreasing operations. Since many of these workers are sometimes
additionally exposed to drugs which might exacerbate any effects of PCE
on the central nervous system, a study was conducted to evaluate the
potential interaction of PCE and such drugs on the behavioral and neuro-
logical function of volunteer subjects.

Six volunteers of each sex were examined and found to be in good health
both mentally and physically. Alcohol in the form of 100-proof vodka
and a mild antidepressant in the form of diazepam were chosen as the two
drugs to be added one at a time to the PCE vapor exposures. All high
dose levels were selected on the basis of an expectant mild but measur-
able behavioral or neurological effect: 0, 25, or 100 ppm PCE; 0, 6,or
10 mg/day diazepam, and 0.0, 0.75, or 1.5 ml vodka/kg body weight. All
exposures were replicated, and testing was performed in a double-blind
mode, Biologic sampling and analysis confirmed the body burdens of PCE,
ethanol, and diazepam during testing.

A battery of neurological and behavioral tests,comprised of the following,
were administered at the peak blood levels of the drugs: Michigan eye-
hand coordination, rotary pursuit, Flanagan coordination, saccade eye
velocity, and dual-attention tasks. In the midst of these tests, the
subjects completed the Lorr-McNair mood evaluation test. In addition,
electroencephalograms were recorded for spectral density analysis during
the exposures.

Data analysis revealed that subjects exhibited a decrement in performance
of at least one test while on each drug alone at the highest dose level,
but no interaction with PCE could be demonstrated in any test for either
combination. In addition, there was no consistent effect of PCE alone

on the EEG of any subject,as had been previously reported for a

different group of subjects. These results lead us to conclude that

under the conditions studied, which simulated worker exposures to PCE
‘and’ the drugs diazepam or alcohol, the subjects demonstrated no decrements
in neurological or behavioral performance that could be attributed to

. the addition of PCE exposure to drug consumption.

Decrements in performance of the Michigan eye-hand coordination, rotary
pursuit, and Flanagan coordination tests due to alcohol consumption
reinforce the known hazard of the use of this drug in the workplace.
Decrements in performance associated with diazepam dosing were more
subtle, with a significant effect on the performance of the rotary
pursuit test only. A repeat finding of a slight but statistically
significant detrimental effect upon the performance of the Flanagan
coordination test at the highest level of PCE exposure was noted.

iii
''''CONTENTS

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''''ACKNOWLEDGMENTS

The following personnel in the Department of Environmental Medicine, in
addition to the cited authors, contributed technical expertise in car-
rying out the study and/or aided in preparing this report: L. Ebert,
H.V. Forster, Ph.D., S.A. Graff, B.S., A.A. Herrmann, M.D., C. Hirt,
B.S., C. Jirka, B.S., S. Kamke, J. Kaufman, M.D., M.L. Pearson, B.S., D.
Shekoski, G. Smith, M.S., R.J. Soto, M.S., T.A. Stewart, and K. Suschil,
A.B. We are also indebted to V. Putz, Ph.D., and C. Xintaras, Sc.D.,
NIOSH, for valuable advice in carrying out the behavioral studies, and
to B.L. Johnson, Ph.D., for assistance in analyzing the EEG data.

vii
''''INTRODUCTION

Perchloroethylene (PCE), chemically named tetrachloroethylene, is widely
used in industry as a dry cleaning and degreasing agent. Its lipophilic
character, stability, and relatively high boiling point of 121° C make
it an ideal solvent for these uses as far as its physical properties are
concerned. However, its pharmacologic property of central nervous
system depression, or narcotic effect, requires that a value be set for
the maximum time-weighted average exposure during which a worker in-
haling its vapor can work safely and free from hazard. The documenta-
tion (American Conference of Governmental Industrial Hygienists, 1971)
for setting the Threshold Limit Value (TLV) for PCE in workroom air at
100 ppm suggests that this concentration will prevent serious narcotic
effect. More recent work from this laboratory (Stewart, et al., 1974)
suggests that the margin of safety of this TLV is rather minimal, even
in sedentary workers, if coordination tests and subjective EEG analysis
of volunteer subjects are used as criteria for measuring narcotic ef-
fect. The question then arises as to the degree of hazard the workman
presents to himself and others if the effect of another "depressant" is
added to any central nervous system depression experienced as a result
of the TLV (OSHA standard) exposure to PCE vapor. The objective of this
study was to answer this question in a laboratory setting.

Ethanol, in the form of alcohol in commercial vodka, was chosen as a
central nervous system "depressant" which is sometimes consumed by
workers and therefore could increase the hazard of simultaneous exposure
to PCE. A second "depressant" drug chosen to be given during PCE ex-
posures was diazepam (VALIUM - Roche). It is widely prescribed on an
outpatient basis for relief of tension and anxiety (Roche Laboratories,
1975) and thus is also available to workers exposed to PCE. Obviously
there are several other drugs that are general depressants of the cen-
tral nervous system (Levine, 1973), but these two were the best candi-
dates for this study because of their widespread use and their predic-
table action. They were given singly, and in combination with PCE
exposure, but never in combination with each other.

Volunteer subjects of both sexes were recruited from the general popu-
lation, and after it was determined that they were medically, physi-
cally, and neurologically healthy, they were asked to participate in
biochemical, behavioral, and neurological testing while being exposed to
no chemicals, PCE alone at two concentrations, ethanol alone at two dose
levels, PCE plus ethanol, both at two levels, diazepam medication alone
at two levels, and PCE plus diazepam medication, both at two levels.

The Occupational Safety and Health Agency (OSHA) standard of 100 ppm was
chosen as the maximum PCE exposure level, and, in order to equilibrate
the body burden rapidly rather than over several hours, subjects exercised

iL
''moderately (approximately 50W) on bicycle ergometers for 1/2-hr early in
each exposure day. The lower level of exposure chosen, wherein no
depressant effect would be expected yet the odor would be detected, was
25 ppm PCE (Stewart, et al., 1974). The two dosages of vodka, given as
approximately 10 to 20% in juice, were selected for each subject indi-
vidually by a physician. The desired blood alcohol levels were 40 and
80 mg/dl, the lower level selected to assure an alcohol taste in the
"cocktail", and the upper level one after which the subjects would not
be inebriated to the point of being ill. These levels were attained
with dosages of approximately 0.75 and 1.50 ml 100-proof vodka/kg body
weight. Diazepam dosages of 6 and 12 mg/day were originally selected as
no-effect and low-effect doses for this medication (Roche Laboratories,
1975). When it was found that the 6 mg/day (2 mg t.i.d.) may have
caused measurable central nervous system depression, the high dose was
reduced by the attending physician to 10 mg/day (5 mg b.i.d.).

The original schedule for the repeated exposures to the PCE, alcohol,
diazepam, and combinations is shown in Table I. As required for any
behavioral testing, control and high dose exposures were replicated in
order to make it possible to estimate any interactive effect on a sta-
tistically reliable basis (Crow, Davis, and Marfield, 1960). The pro-
cedures used for testing are described in detail in the following sec-
tion on METHODOLOGY. In the subsequent section on TEST CONDITIONS, the
conditions that existed as the subjects underwent behavioral and neuro-
logical testing are described, while the next section reveals the results
of this testing. The final section,entitled DISCUSSION, assimilates the
results of the many tests carried out and puts them into a proper per-
spective regarding the overall CONCLUSIONS of the study.
''METHODOLOGY
SUBJECTS

Recruitment of volunteer subjects was carried out by placing a notice in
the College's What's Happening sheet, contacting former subjects, and by
a commercial temporary help organization. Prospective volunteers were
briefly informed of the purposes and terms of the study and then given
comprehensive medical examinations. This examination included the
following: the completion of a health questionnaire by the prospective
subject; a history and physical examination completed by the examining
physician; an ORTHO-RATER visual performance profile; a 12-lead electro-
cardiogram; a neurological examination including cranial nerves, mus-
cles, reflexes, gait, alternating motor rate, and coordinafion, by the
physician; a complete blood count; a urinalysis (COMBISTIX —- Ames); a
pregnancy test (PREGNOSIS) for females; and a battery of clinical
chemistries (CHEM-SCREEN-25, Medpath, Inc., including calcium, phos-
phorus, BUN, creatinine, BUN/creatinine ratio, glucose, uric acid, total
protein, albumin, A/G ratio, SGOT, SGPT, LDH, total bilirubin, direct
bilirubin, alkaline phosphatase, gamma glutamyl-trans-peptidase, amyl-
ase, sodium, potassium, chloride, cholesterol, beta-lipoproteins, total
lipids, and thymol turbidity).

Prospective subjects who were found to be physically fit for the study

by the passing of the comprehensive medical examination were then
oriented more completely by a faculty member regarding the purpose,
procedures, risks, benefits, and alternatives of this study. In addition,
they were told that they could withdraw from the study without prejudice

at any time, Each prospective subject received a compilation of printed
information, They were encouraged to ask questions if there were unresolved
problems, They were then asked to complete the Informed Consent Questionnaire
(Appendix IL) and NIOSH Participant Document giving informed consent.

All volunteers participated in a pulmonary function test (computerized
expirogram) and neurological test (electroencephalogram) before the exposures
began in order to obtain their baseline values.

The health of each subject was continually monitored with daily» brief
medical examinations prior to exposure, including blood pressure,
temperature, subjective signs or symptoms, numbers of hours sleep the
previous night, alcohgl consumption since the previous exposure, and
urinalysis (COMBISTIX - Ames), and with weekly complete blood counts
and clinical chemistries (CHEM-SCREEN-25). Whenever any out-of-normal
range values appeared, additional testing was carried out as necessary.

The electrocardiogram (EKG) of each subject was monitored intermittently
while in the chamber and continuously while exercising. This was

3
''accomplished with telemetered lead II EKGs using SPACELABS, INC. Biotel
170 transmitters and receiver/cardiotachometers, and a single channel
recorder for permanent recordings.

Subjects were paid weekly for the total number of hours spent at the
laboratory. At the end of the study, each subject who had completed the
Study was paid a bonus.

EXPOSURE LEVELS

The exposures to PCE were conducted in a controlled-environment chamber
6.1 x 6.1 x 2.4 m in size, which was adjoined by al x1.5 x 2.4 m
toilet facility and a 2.1 x 2.3 x 2.4 m room shielded against electro-
magnetic radiation. Both the toilet facility and the shielded room were
ventilated by air from the chamber. This three room complex had its own
independent air handling system and all outside doors were self-sealing
when closed. Air flow through the complex was approximately 42 cu m per
min and approximately 25% of this flow was exhausted, causing a slight
negative pressure within the complex at all times. Air temperature was
maintained at 21-22° C while relative humidity ranged between 45-55%.
The PCE vapor was introduced by sweeping the concentrated vapor from a
warm flask with a stream of air into the chamber's circulating air. A
reciprocal dual-piston pump (MODERN METALCRAFT) maintained a steady flow
of liquid PCE into the flask. A manually operated set of coordinated
valves in the air handling system was used to control the concentration
of PCE in the chamber atmosphere. This concentration was continuously
recorded by an infrared spectrometer (MIRAN I, Wilks Scientific Corpora-
tion) equipped with a 20-m path-length gas cell which was continuously
flushed with air drawn from the chamber through a 6.35-mm diameter
polyethylene tubing. The absorbance at 10.9 u was measured through a
path-length of 5.25 m. The infrared signal to the recorder was monitored
each second by an on-line PDP-12 (Digital Equipment Corp.) computer,
which displayed the mean vapor concentration, as compared to standards,
for each 30-sec time interval of exposure and calculated the daily time-
weighted average exposure for each individual subject. Calibration
standards of PCE in purified air were prepared in saran bags and ana-
lyzed before and hourly during each daily exposure.

A second independent chamber monitoring system using the gas chromatograph
(GC) as the measuring instrument was used for back-up of the infrared
System. The GC system was equipped with an automatic sampling device
that swept a sample of the chamber atmosphere into the carrier gas (N,)
of the chromatograph every three min. The Varian Aerograph Model 900 GC
was fitted with a stainless steel column, 36 x 0.32 cm, packed with
Porapak Q, 60/80 mesh. The column was preconditioned at 200° C for 24

hr prior to its use. Throughout the study, the column was kept at 180°
when it was not in use. The operating conditions of the GC were:

carrier gas flow rate of 35 ml/min, column temperature, 180° C; injection
port, 150° C; and flame ionization detector, approximately 250° C. Peak
heights of chamber atmosphere samples were compared to peak heights of
calibration standards prepared in saran bags and swept through the

System from the chamber. Calibration standards were prepared indepen-
dently by two individuals, and the measured concentrations of PCE in the

4
''chamber atmosphere by the two monitoring systems had to agree before
subjects were allowed to enter the chamber. The two systems were cross-—
checked frequently during daily exposure to assure that the concentration
in the chamber was correct.

A commercial vodka (SMIRNOFF, 100-proof) was added by measuring cylinder
to a partial cup of juice (tomato or orange, subject's choice) to give a
final ethanol concentration of approximately 20% in each "cocktail".

Ice was added. The total dose of ethanol was divided equally between
two "cocktails", each given to the subjects for sipping over a 15-min
period. On all non-alcohol days, the vodka was replaced with juice.

The diazepam (VALIUMS) dosage and placebo in capsule form were prepared
by a registered pharmacist. A number of 2-mg tablets of VALIUM were
ground in a mortar and pestle and refilled into an equal number of
gelatin capsules for the low dose of 6 mg/day (2 mg t.i-d. at mealtime).
Placebo for this dose level was prepared by filling corn starch powder
into the same size gelatin capsules. The subjects were given sufficient
capsules containing either the diazepam or placebo each Friday afternoon
to start dosing that evening and continue through the weekend. Then on
Monday morning they were each given an additional number of capsules to
last through the week to Friday noon. During the exposure days, the
second capsule of the day was consumed with the first glass of juice
rather than with lunch. After the first week of study with diazepam at
6 mg/day and resultant drowsiness in some subjects, the decision was
made by the physician to reduce the high dose from 12 to 10 mg/day. The
Pharmacist prepared 5-mg capsules (5 mg b.i.d.), and similar corn starch
placebos, which the subjects were advised to take at breakfast and
supper, except for the exposure days when they took the second capsule
with the juice while in the chamber. As will be noted in the schedule
later, this dose was given to subjects an hour prior to behavioral
testing.

EXPOSURE SCHEDULE

As shown in the original schedule (Table 1), exposures were to take
place over eleven weeks during a three-month period. The timing of the
plan required that this schedule be carried out between October 1 and
December 25, and allowed only the Thanksgiving week for possible re-
peats. Fortunately, a minimum of repeats was required. Some of the
testing equipment, specifically that for the electroencephalograns,
saccade velocity test, and dual-task test,was not totally operable
during the first three weeks of the schedule. Because Week 1 was a
training week, and Week 2 was scheduled to be repeated as Week 6, these
were no problem. Only Week 3 needed to be repeated, and this was ac-
complished (see Table II) by moving Week 12 to Week 9, moving Week 11 to
Week 12 and repeating Week 3 as Week ll.

BIOCHEMICAL
Breath samples were obtained from subjects by the 30-sec breath-holding
technique, with subsequent collection of the alveolar breath in SARAN

film bags (Stewart, Hake, and Wu, 1976). When collected in the chamber,

5
''care was taken to exclude chamber air. The breath samples were analyzed
for PCE, and ethanol when needed, on the same day as collected.

A Varian Aerograph Model 2700 gas chromatograph (GC) equipped with a
hydrogen flame ionization detector was used to measure the PCE and
ethanol in aliquots removed from the breath bags by syringe. The GC was
fitted with a stainless steel column, 1.8 m x 0.32 cm, packed with FFAP
on Chromosorb W, 80/100 mesh. The column was preconditioned at 200° C
overnight prior to use. The operating conditions of the GC were:
helium carrier gas flow rate of 40 ml/min; column temperature, 100° C;
injection port temperature, 210° C; and detector temperature, 220° C.
Standards at a minimum of three concentrations of PCE, and ethanol when
needed, were prepared daily in purified air. A single 1-ml injection
was normally made from each breath bag, except when overlapping or poor
peaks were encountered. The concentrations of the PCE and ethanol were
obtained by direct comparison of peak heights to standards, and were
reported in ppm (volume per volume).

All blood samples were withdrawn with Vaoutetmer™ tubes from antecubital
veins, filling the tube to equalize the inner pressure to atmospheric.

A 2-ml aliquot was removed and introduced into a 40-ml capped (Saran
film liner) glass vial containing 1 ml aqueous solution of 1 ppm ethyl
benzene as internal standard for PCE, and 50 mg/dl isopropyl alcohol as
internal standard for ethanol when needed. The mixture was shaken and
warmed to 37° C in a water bath. Two l-ml aliquots of the headspace
were removed for PCE analysis, using the same GC and conditions as for
the breath samples. The blood ethanol was assayed by removing two 1-ml
aliquots from the head space of the vial and injecting into a second GC
with a Porapak Q, 60/80 mesh column. The operating conditions for this
GC were slightly different with a column temperature of 180° C; injec-
tion port, 180° C; and detector, 250° C. A second GC was needed for the
ethanol assay because of the much higher concentration of this volatile
in the blood. Calibration curves (peak height ratio of PCE or ethanol
to appropriate internal standard versus concentration) were prepared
daily. The concentration of PCE and ethanol in the unknown were ob-
tained directly from the calibration curves and reported as ppm (by
weight, assuming sp. gr. of blood equals one) of PCE and mg/dl of
ethanol.

The method of Garriott (1975) was followed for the analysis of diazepam
in blood. Five ml of blood was assayed in duplicate for this medi-
cation. The procedure involved an extraction with n-butyl chloride from
blood made basic with conc. ammonium hydroxide, re-extraction into
aqueous HCl, and final extraction by chloroform from the alkalinized
aqueous solution. Aliquots of the chloroform extract were injected into
a GC and peak heights were compared directly to standards. Diazepam
blood levels were reported in yug/dl.

BEHAVIORAL

Behavioral testing was carried out immediately upon entry into the
chamber (saccade velocity and Michigan eye-hand coordination) and again
50 min after exercise (complete battery). The Michigan eye-hand

6
''coordination, rotary pursuit, and Flanagan coordination tests were
carried out in the environmentally-controlled chamber, but they were
separated by carrel walls or a curtain, while the saccade velocity and
dual-attention tasks tests were carried out in isolation in the shielded
room adjacent to the chamber.

The Michigan eye-hand coordination test was developed by Pook (1967).
The hardware consisted of a flat,eight-inch square board with 119 0.32-
em diameter holes which were connected by a zig-zag line (see Figure 1)»
The subject, following the line from start to finish, placed a stylus to
the bottom of each hole as rapidly as possible. Timing with an electri-
cal stop clock was started with the withdrawal of the stylus from the S
hole, and the elapsed time to the insertion into the F hole was recorded.
A subject who missed a hole in the zig-zag line was required to start
over. Each session consisted of four trials from which the elapsed
times were totaled for that session's score. The instructions for the
staff person giving the test are given in Appendix II. Each session
took approximately 5 min to complete and record the testing.

The rotary pursuit test was carried out with a photoelectric rotary
pursuit apparatus with a circular template (Lafayette Instrument Co.,
Model 30013). In this test, the subject, standing at a comfortable
distance from the table on which the apparatus was placed, was required
to follow the light in its horizontal, clockwise, circular path on the
top of the apparatus with a wand containing an electric eye. The wand
was held in the hand used for writing. The sensitivity setting of the
light was always at 10 units. After a 30-sec warm-up at 10 rpm, the
subject "pursued" the light for 45-sec intervals at 15, 30, 45, and 60
rpm. The apparatus measured the time-off target in hundreths of a
second, and the "errors" or number of times off and back on the target,
during each 45-sec trial. The staff operator recorded these numbers for
each 45-sec interval. The instructions for the staff persons giving the
test are given in Appendix III,Each session took approximately 5 min to
complete and record the testing.

The Flanagan coordination test used is published by Science Research
Associates, Inc., 259 E. Erie St., Chicago (Flanagan Aptitude Classi-
fication Test, 7A, Coordination). This test required that the subject
rapidly follow a spiral pathway (see Figure 2) with a pencil, touching
the sides of the pathway as few times as possible. The staff operator
Started each trial with the words "pencil down, ready, begin." The
subject was allowed 40 sec to complete each of six spirals. The first
two were considered practice and the last four were scored and totaled.
The total score depended upon the longest distance attained in each
spiral minus the number of times the sides of the spiral pathway were
touched with the pencil. This test took approximately 5 min to perform.
Scoring was carried out by visual inspection of each spiral, and though
done by several staff persons, the same person scored all of the tests
for a given subject throughout the entire study.

The saccade velocity test, which used electrooculography (EOG), was
furnished by NIOSH. The design was based upon work by Dr. Robert

Baloh and associates at UCLA (1976). Horizontal eye movements were

7
''differentially recorded from electrodes fixed lateral to both outer
canthi and to the forehead for reference ground while the subject's head
was mechanically fixed using a bite bar. The stimulus used to elicit
eye movement was a semi-circular array of 32 small red lights, 15 cm
apart, arranged on a black plywood stand and approximately 76 cm from
the subject's eyes. A programmable digital-logic system was used to
control the lighting of the stimuli, and a FM tape recorder was used to
record the amplified electrooculogram. This test was carried out in a
completely isolated, weakly lit room adjacent to the chamber, with the
subject only required to stay alert and turn the eyes to the red stimu-
lus light as rapidly as possible. This test required approximately 5
min.

The dual-attention tasks test used the same room and equipment setting
as the saccade velocity test. The semicircular array of red lights
included one white light at the center of the arc directly in front of
the subject. The two tasks, as reported by Moskowitz and Sharma (1974),
were differentiated by the blinking or non-blinking of the white light.
The blinking task required that the subject count the random number of
times the white light blinked, and release a hand-held microswitch as
rapidly as possible when a peripheral red light appeared (1 sec dura-
tion). A tone signaled the start and the stop of each trial, and there
were ten trials in each session. Programmed equipment allowed the
center white light to blink randomly 11 to 19 times during each 20-sec
trial, and a peripheral red light to light at random two to four times.
Timing instrumentation recorded the red light response time, and the
subject entered the number of blinks of the white light on a 10-digit
keyboard. The non-blinking white light task simply required the subject
to release the hand-held microswitch as rapidly as possible when a
peripheral red light came on, meanwhile focusing the eyes on the white
light. Again, the peripheral red lights appeared two to four times over
each of ten 20-sec trials. The timing instrument recorded the response
time. The total elapsed time for this test was approximately 10 min.

NEUROLOGICAL

Within five min of entry into the environmental chamber, and within ten
min prior to exit, each subject performed a modified Romberg and heel-
to-toe equilibrium test which was videotaped for later inspection if
necessary. The test consisted of standing upon each leg singly with
arms at the side for a minimum of 3 sec, and walking heel-to-toe in a
straight line for approximately 1.5 m. This was first done with the
eyes open and then repeated with eyes shut. A staff person, viewing the
performances from outside the chamber, recorded each subject's perfor-
mance as +, +, or -.

For the spontaneous electroencephalagrams (EEGs), the subject sat
upright in a comfortable recliner chair with a back high enough to fully
support the head and neck. The chair was located in isolation in the
shielded room adjacent to the chamber. There was no room lighting
during the tests. The EEGs were recorded on an eight-channel GRASS
Model 7 polygraph using gold-plated silver electrodes oriented on the
scalp according to the 10-20 International System (Jasper, 1958). The

8
''leads utilized and their corresponding electrode geometry are shown in
Figure 3.

The first four channels listed in Figure 3 were linked to the analog/dig-
ital converters of a PDP-12 computer (Digital Equipment Corp.). Power
spectral analyses of these channels were obtained by taking fast Fourier
transforms of the data sampled at a rate of 256 Hz for four pairs of
four-sec epochs, or a total of 32 sec. The frequency range of the
spectra was 0 - 31.75 Hz in 1/4 Hz intervals. The computer program
printed and plotted the spectral energy within 1.75-Hz bands from 0 to
31.75 Hz, the spectral energy within the alpha (8 - 13.75 Hz), delta
(0.25 - 3.75 Hz), theta (4.00 - 7.75 Hz), and beta (14.00 -30.00 Hz) EEG
bands, and the "dominant frequency," or the frequency that had the
maximum spectral amplitude. A three-point moving average smoothing
filter was applied to the raw spectral estimates prior to any compu-
tations.

The power spectra were generated three times during the exposure day,
once shortly after entry into the chamber and twice approximately four
hours later. During each session, three 32-sec periods were analyzed
and stored on tape for later processing. These sessions were conducted
with the eyes closed, and were each preceded by having the subject
quietly relax in the darkened room for two min, after which he or she
clapped the hands loudly five times. This procedure standardized the
alertness of the subject. Each session required approximately ten min.

PHYSIOLOGICAL

Exercise was carried out on four MONARK (GCI, Stockholm) bicycle ergome-
ters at a pedal rate of 60 rpm. Loads were individualized prior to
exposure in order to increase the average heart rate by 30 beats/min

over each subject's normal resting heart rate. Total ventilation could
be expected to increase three- to four-fold over sedentary levels (Robin-
son, 1974). Heart rates were determined by EKG telemetry as described
earlier. Subjects used the same bicycle each day, adjusting the seat
height to comfort for the 30-min session.

SUBJECTIVE RESPONSES

Mood assessment by completion of a subjective feeling inventory form
based upon the Lorr-McNair mood adjective checklist (McNair and Lorr,
1964) was measured on a daily basis. Each subject selected a personal
psuedonym for the study, and entered this psuedonym and the date at the
top of the form. The form contained 56 adjectives or phrases to de-
scribe mood and four phrases that required the following of simple
directions (see Appendix IV). Five variations of adjective sequence
were used in order to prevent memorization. Choice of boxes

to be checked for each adjective were "not at all, a little, quite

a bit, and extremely.” The subjects were advised to "check the appro-
priate box - which indicates how you feel at that moment. Use your
first response." This form took approximately 3 min to complete.

For scoring, the adjectives were arranged into nine groups according to
Davis (1971); depression (9 adjectives), carefree (9), friendliness (6),

9
''hostility (5), anxiety (7), cognitive gain (5), guilty-ashamed (3),
fatigued (3), and miscellaneous (9), and the group of simple directions
(4). In the last group, a correct answer was simply scored one point,
and zero if incorrect. In all other groups, "not at all" received 0
value; "a little’ - 1; "quite a bit" - 2; and "extremely" - 3. The
psuedonym code was broken by subject number only after the entire test-
ing and scoring were completed.

The subjective response form completed each hour when in the chamber is
shown in Appendix V. Rows were provided for the keywords: headache,
nausea, dizziness, abdominal pain, chest pain, ENT irritation, other,
and odor, with the adjectives mild, moderate, and strong. Columns were
addressed: immediate, 1/2, 1, 2, 3, 4, and 5 hr, and 1/2 hr post. The
subjects were advised to record only abnormalities with an appropriate
adjective, drawing a line through all rectangles when no abnormal sub-
jective response was present. These responses were checked daily by a
Physician, and the forms were scored simply by noting the number of
subjects marking a specific response and the total times a response was
noted.

The form used for staff assessment of the subjects’ mood and behavior in
the environmentally-controlled chamber is found in Appendix VI. These
were completed at the end of each day, starting on Day 5 of Week 3 by
five staff persons who worked with the subjects but were not informed of
the PCE concentration or drug- or alcohol-dose levels.

DATA ANALYSIS

Methods used for the analysis of the voluminous data generated in this
study were several in number ,depending upon circumstances. Data to
establish the TWA of the PCE exposures was handled by computer fitting
of standard curves and subsequent calculation of each 30-sec unknown and
averaging during chosen time periods. PCE, ethanol, and diazepam bio-
chemical levels were treated by computerized two-tail t-test to deter-
mine interactive and gender effects.

Data from the subjective feeling inventory were entered into the com-
puter and analyzed for variance from the control mean by the t-test
method. Subjective response and staff assessment of subjects' mood
comparisons were made by simple calculation of means for each of the 18
exposure conditions.

All of the behavioral responses were quantitated by individual subject
and day of study (1 through 74). Concentration codes were as follows:
PCE - 000, 025, and 100, corresponding to 0, 25, and 100 ppm PCE; di-
azepam — 00, O01, 06, and 10, corresponding to no capsules, placebo
capsules, 6, and 10 mg/day; and alcohol - 000, 075, and 150, corres-
ponding to doses of none, 0.75, and 1.5 ml 100-proof vodka/kg body
weight. The compiled raw data for the Michigan eye-hand coordination,
Flanagan coordination, and the rotary pursuit tests were keypunched and
analyzed by computer at the Medical College of Wisconsin Computer Cen-
ter, while the data from the saccade velocity and dual-attention tasks

10
''tests were sent to NIOSH (Cincinnati) for analysis,as per the contract.*
EEG power spectra tapes were first analyzed in the Department to prepare
visual spectra and compute summary descriptors and then the resultant
descriptors were statistically analyzed by the Computer Center. Missing
data were supplied by the usual method (Yates) of handling missing data.
Only the responses from the nine subjects who finished the study were
analyzed.

Computerized programs computed mean group responses for the behavioral
tests for each day of testing. Because of the learning or conditioning
which occurred during the three-month period of testing, a "trend ad-
justed t-test" was used to plot the means versus each daily exposure
condition. For the trend adjusted t-test, a linear trend line was fit
for each subject using the control days data only. The regression
response for each day was subtracted from the observed response. Then,
for each day the mean of adjusted observations was tested versus zero.
Since each subject had an equal number of observations on each day, the
overall trend line represented the (unweighted) average trend line of
the nine subjects. This overall trend line, with 95% confidence bands
for a future average of nine subjects, was drawn on the three month
graph, along with the daily means.

The continuous variables were assessed by analysis of variance tech-
niques. Multiple regression equations, using the baseline or control
trends data, were used to evaluate the treatment effects. Analysis of
variance tables were used to display the results of significance testing
and the multiple regression equations were used to depict the PCE,
diazepam, and alcohol interactions, both significant and nonsignificant.
Using a block-design type of analysis, with the subjects as blocks
(random) and treatments specified by combinations of PCE with diazepam
or PCE with alcohol (fixed effects), separation of the interaction
effects was achieved.

 

*The analysis of the dual-attention task data is found in the Adden-
dum. Technical difficulties to date have precluded NIOSH analysis of
saccade velocity, the analysis of which will be reported separately.

11
''TEST CONDITIONS
SUBJECTS

Eight males and six females were judged by the examining physician to be
those best qualified for the study from nine males and eleven females
who were given comprehensive medical examinations. Neurological examina-
tion, eye tests, physical condition, past medical and work history, EKG,
and pulmonary function tests revealed that each of these persons was
qualified to carry out the behavioral/neurological testing under the
required testing conditions. All personal medical data concerning these
persons are secured in the Department's confidential files, available
upon written request to the individual concerned. One male person
failed to appear for the orientation and another failed to return after
the first day of training. All persons present for orientation signed
the Participant Document form. Table III lists the ages, heights and
weights of the six males and six females who volunteered for and then
began the study. All were Caucasian. They were assigned subject
numbers, three having been subjects in previous studies (more than six
months previous) and these retained their original subject number. All
data generated in the study were collected by subject number, or pseu-
donym (mood evaluation only).

The six male and six female subjects were further divided into Groups A
and B for study purposes. As seen in Table III, there were three subjects
of each sex in each Group, selected simply by consecutively assigned
subject numbers.

There were 55 training and exposure days during the study. Table

IV gives the attendance summary of each subject. Subject 326 withdrew
from the study when her previous job again became available, and subject
331 withdrew when his spouse suffered an injury that forced him to stay
at home. Subject 123 was withdrawn from the study after a week's ab-
sence with no excuse. All other subjects finished the Study. Three
subjects, 329, 330, and 334, were present but not participating on four
days while medical problems were being resolved. Absences were most
often due to the subject's reporting by phone of bad colds or flu-like
Symptoms. Several absences were due to trips out-of-town for personal
reasons. Only one subject, 330, was present for all 55 training and
exposure days.

Daily medical surveillance by the attending physician, using the testing
Procedures listed in the METHODOLOGY section and further follow-up when
necessary, provided assurance that each subject entering the exposure
chamber each day for testing was in good health. Weekly laboratory
studies and final comprehensive physical examination confirmed that
each subject remained in good health throughout the study. Surveillance

12
''of EKG's on the scope during subject exercise and daily review of inter-
mittent EKG tracings revealed no deleterious effect of the study upon
the electrical activity of the heart of any subject.

EXPOSURE LEVELS

The PCE used for this study was obtained from the Aldrich Chemical Co.,
Inc. (catalog no. T750-0, tetrachloroethylene, 99%, MW 165.83, d 1.623,
bp 121°) in 4-kg bottles. Each bottle was sampled for identity confir-
mation by infrared spectroscopy. Table V lists the time-weighted
average (TWA) PCE concentrations, and the standard deviations (SD), that
were measured in the controlled-environment chamber by the infrared
monitoring system. Each pair of subjects entered the chamber at 10-min
intervals, thus the 5-1/2-hr TWA for each pair differed slightly from
that found in the table, but the difference from that reported was never
more than 0.5%.

Table VI lists the daily total ml of 100-proof vodka consumed in two
"cocktails" by each subject during the two weeks that ethanol was
studied. These levels were chosen by the physician based upon weight
and probable blood levels of ethanol that would be attained. Subject
326 had already withdrawn from the study at Week 5, and subject 123 and
331 had withdrawn by Week 10. Although the amount of conversation in
the chamber was greater during these two weeks, no subject became nau-
seated or ill from this dose of vodka. All subjects were encouraged not
to consume any form of alcohol outside of the tests. However, most of
the subjects reported drinking socially in moderation after the test day
was completed. Blood and breath ethanol levels found during the test
day will be discussed in a later section on Biochemical Measurements, as
will the blood diazepam levels.

Although subjects were continually reminded to take the diazepam doses
that were required while away from the laboratory, many forgot or were
unable to comply. Listed in Table VII are the exceptions to the pre-
scribed diazepam and placebo dosages. Every dose that was to be ingested
while in the chamber was ingested unless the subject was absent. In

some cases the breakfast dose was taken when the subject arrived at the
laboratory because there was no "convenient" time beforehand. During

the high dose diazepam and placebo weeks (Weeks 7 and 8) and the high
ethanol and last diazepam weeks (Weeks 10 and 11), all subjects were
transported between their place of residence and the laboratory by taxi.

DAILY SCHEDULE

The schedule for the 55 training and exposure days that were included in
this study was described under METHODOLOGY, Exposure Schedule; therefore,
this section will deal with the daily schedules.

During the 2-1/2 days of training, all subjects carried out the Michigan
eye-hand coordination test six times, the rotary pursuit test six times,
and the Flanagan coordination test seven times. They were oriented on
each of the other tests by practical demonstrations, and rode the bicycle
ergometer while heart rates were determined. These training days allowed

13
''each subject to become thoroughly acquainted with the testing procedures,
and brought them near their individual plateau performance on those
tests where practice affected the performance.

It was determined before the exposure days began that it would be diffi-
cult for all 12 subjects to be involved in every test on a daily basis

for two reasons: 1) there was insufficient time, and 2) it was objection-
able to the subjects to have both the saccade velocity and EEG electrodes
attached every day for 53 days. Therefore, the 12 subjects were divided
into Groups A and B, as noted in the Subjects section. Group A subjects
underwent EEG testing and Group B the EOG during the alcohol (ethanol)
dose weeks and certain control and placebo days, while the reverse was
true during diazepam dosing and alternate control and placebo days. The
schedule shown in Table II includes the notations for which Group was
scheduled to undergo EEG testing. The other Group automatically underwent
EOG testing. Another complication to overcome was the fact that, for
almost all the behavioral and neurological testing, only one piece of
equipment was available, and only one person at a time could be tested

in the isolation booth for EEG, EOG, or the dual tasks test. Therefore,
each Group was further divided into three subgroups of a male and female
(subgroups 1 and 2, 3 and 4, 5 and 6). Alternate subgroups from A and B
entered the chamber at 10-min intervals in the same order on a daily
basis.

The first pair of subjects (1 and 2, EOG) entered the chamber at 8:30 AM
and exited at 2:00 PM with an elapsed time of 5-1/2 hr or 330 min.

Their schedule using elapsed time in min was as follows: 0 to 5,
Romberg and heel-to-toe and EKG strip; 5 to 35, saccade velocity (EOG)
and Michigan eye-hand; 35 to 65, exercise with EKG monitoring; 65 to 95,
"cocktails"; 95 to 115, rest with blood and breath sample at 112; 115 to
130, Michigan eye-hand and rotary pursuit; 130 to 140, mood and Flanagan
coordination; 140 to 170, saccade velocity (EOG) and dual tasks; EKG
Strip at 250; 225 to 255, lunch; 320 to 325, Romberg and heel-to-toe and
EKG strip; 330, exit chamber. The second pair of subjects (1 and 2,
EEG) entered the chamber at 8:40 AM and exited at 2:10 PM. Their sched-
ule was as follows: 0 to 5, Romberg and heel-to-toe and EKG strip; 10
to 20, EEG; 25 to 40, Michigan eye-hand; 40 to 70, exercise with EKG
monitoring; 70 to 100, "cocktails"; 100 to 120, rest with blood and
breath sample at 118; 120 to 135, Michigan eye-hand and rotary pursuit;
135 to 145, mood and Flanagan coordination; EKG strip at 240; 215 to
245, lunch; 260 to 320, two sets of EEGs; 320 to 325, Romberg and heel-
to-toe and EKG strip; 330, exit chamber. The alternating subgroup entry
by twos each 10 min continued through 9:20 AM, and subsequent testing
followed the alternating schedules (see Appendix VII).

In summary, each subject was in the chamber 5-1/2 hr daily. Within 5
min of entry and 10 min of exit, each subject performed a Romberg and
heel-to-toe equilibrium test. Within 30 to 60 min of entry, each sub-
ject carried out the Michigan eye-hand coordination test. During this
same 30-60 min, before exercise, "alcohol" subjects had an EEG while
"diazepam" subjects had an EOG. After this 30-60 min period, each
subject carried out the following sequence: 30 min of exercise on a
bicycle ergometer; 30 min of sipping two "cocktails," with medication

14
''during the first if it was a diazepam or placebo week; 20 min of rest,
with a blood and breath sample at 18-20 min; 15 min of Michigan eye-hand
coordination and rotary pursuit tests; and 10 min of Flanagan coordin-
ation and mood tests. The "diazepam'' subjects then repeated the EOG and
carried out the dual tasks test over the next 30 min, while the "alco-
hol" subjects were given EEGs after lunch.

BIOCHEMICAL

The results of the biochemical measurements made on blood and breath
samples revealed that all subjects carried significant body burdens of
the chemical or chemicals under test at the time that behavioral studies
were carried out.

Because of the voluminous nature of the individual analyses, the daily
results were averaged by sex for this report. The results of the
analysis of PCE in the venous blood samples taken just prior to behavioral
testing (2' of exposure) are given by week in Tables VIII to XVIII,
along with pre-exposure (baseline) levels on many days. As had been
expected, exercise had a marked effect upon the PCE blood levels. These
values at 50 min after exercise were found to be three to six times
higher than the venous blood levels of sedentary subjects exposed to
equivalent levels of PCE vapor in this laboratory previously (Stewart,
et al., 1974) (8.25 vs 1.12 to 2.95 ppm). As was also noted previously,
PCE is measureable in the venous blood for many hours after exposure;
however, the levels were generally below 0.5 ppm 18 hr after a 5-1/2 hr
exposure to 100 ppm.

Mean PCE breath concentrations, baseline, after two hr of exposure, and
at 15 and 30 min post exposure, are given by week in Tables XIX through
XXIX. Breath concentrations of PCE at 50 min after exercise were ele-
vated approximately 50% over those from previous studies with sedentary
subjects exposed for 3 hr to 100 ppm PCE. The post exposure breath
levels were unaffected by the exercise early in the exposure period.
They fell between levels from 3- and 7-1/2-hr exposures of sedentary
subjects testcd previously (Stewart, et al., 1974).

The mean blood and breath ethanol concentrations found in the samples
taken just prior to behavioral testing during Weeks 5 and 10 are listed
in Tables XXX and XXXI, respectively. The individual values varied
considerably as noted by the ranges, also listed. During Week 5, the
low dose week, both male and female subjects averaged just under 50 mg
% ethanol in blood,except on Day 1 when both were much lower. During
the higher dose week, Week 10, male subjects averaged 61, while female
subjects averaged 65 mg % ethanol in blood. There was a larger dif-
ference in the breath ethanol levels between the low and high doses, an
average of 150 vs 255 ppm, respectively. The latter is more represent-
ative of the general difference in doses during these two weeks.

The mean diazepam blood concentrations for the weeks of diazepam dosage
are given in Tables XXXII, XXXIII, and XXXIV. The blood levels of
diazepam were generally in the same range during Week 7 as during Week
3 despite a 66% increase in daily dose. However, the return to the

15
''lower dose during Week 11 resulted in lower blood levels than during the
first week of identical dosing. This phenomenon is probably related to
the induction of enzymes that metabolize diazepam, giving the lower
levels during the weeks after induction (Sellman, et al., 1975).
Included in each table are the results of spot checking of diazepam
blood levels during the week after dosing. None was ever detected
during those weeks. However, it should be pointed out that we were
operating near the lower detection limits of the analysis procedure for
diazepam, even during the weeks of diazepam dosing. It can be assumed
from the results, but not proven, that no mistake in dosing with the
wrong capsules occurred.

In the tables already discussed, means were derived from all analytical
data that were available each day. In further development of the
effects of the combined treatments upon each biochemical level in order
to determine whether there was an interaction between PCE blood levels
and alcohol or diazepam consumption, blood values from the four male
subjects who finished the study (nos. 117, 332, 333, and 334), and the
four female subjects who had the best attendance record (nos. 95, 328,
329, and 330) were studied. Values for blood and breath when no diazepam
or alcohol were given, including placebo days, were meaned, and compared
to either all alcohol days, regardless of dose, or all diazepam days,
regardless of dose. The results are shown in Table XXXV. At 25 ppm
exposure concentration, alcohol significantly increased the PCE blood
level (p < 0.01), but did not increase it at 100 ppm. Diazepam had no
effect upon PCE blood levels at 25 or 100 ppm PCE exposure. A similar
Picture emerged when comparing breath levels from samples taken at the
same time as the blood samples (2 hr into the exposure). Breath sample
values from 30-min post exposure indicated a significant effect of
alcohol at both levels of PCE exposure; however, the 100 ppm PCE and
alcohol combination resulted in a significantly lower breath PCE level
in contrast to the 25 ppm where it was higher. The meaning of these
results is unclear. Because the alcohol was consumed almost five hours
earlier, it certainly was all metabolized by the time of this breath
sample and should have had no direct effect. If the effect is real, it
must be an indirect effect.

The difference of blood levels between male subjects and female subjects
at two hours into the daily study was calculated for all treatments
combined and neither blood nor breath levels were statistically different
(p > 0.10) by the two-tailed t-test (8 pairs of means, t = 0.623).

Alcohol blood and breath levels of the eight subjects were found to both
be significantly greater during the higher alcohol versus the lower
alcohol week (bloods: means of 43.9 and 60.9 mg/dl, A = 17 mg/dl, t =
3,79, p < 0.01; and breaths: means of 149 and 256 ppm, A = 108 ppm, t=
-6.10, p<0.0005). However, diazepam blood levels were highest the
first week of the lower dosage (Week 3), the mean being 18.46 + 4.76
ug/dl. During the week of higher dosage (Week 7), the mean dropped to
17.51 + 6.65 ug/dl. However, by paired t-test, this mean was signif-
icantly higher (p < 0.05) than the second week of lower dosage (Week
11), the mean for this week falling to 12.07 + 4.52 ug/dl. This re-
sponse was assumed to be due to more rapid metabolism of the diazepam

16
''after enzyme induction during the first week of dosage (Sellman, et al.,
1975).

BEHAV LORAL

As noted in previous sections, a great amount of effort was made to
reduce the variations in the parameters, other than PCE, ethanol, and
diazepam levels, that might affect test scores. In addition, efforts
were made to keep the "double-blind" aspects of the study intact, with
both the staff supervising the testing and the subjects unaware of the
exposure conditions. As with any study of this magnitude and length,
certain unavoidable problems presented themselves that may have had some
unknown affect on the individual's particular performance, or the
group's performance. Deviations that could affect performance were
noted each day by the staff psychologist and the physician. A list of
these is presented in Table XXXVI. Also noted are equipment failures.
Data known to be affected were removed from further analysis.

Problems with the equipment during behavioral testing usually invalidated
the data obtained. One particular problem was the dual-attention tasks
test wherein the paper tape reader that presented the stimuli to the
subjects malfunctioned randomly through Day 2 of Week 4. All of the
previous data were invalidated. Even after repair, there were problems
with the recording of the number of times a subject noted that the white
light blinked. Therefore additional data were discarded. Another
instrument that malfunctioned occasionally was the rotary pursuit, where
unpredictable stoppage of the rotating light occurred on a few days.

Also noted in Table XXXVI are minor medical problems and some outside
influences that may have had some bearing on behavioral test scores.

On the last day of the study, all the remaining nine subjects were asked
to complete a debriefing questionnaire after testing was completed and
prior to actual debriefing. The questionnaire and the results are shown
in Appendix VIILThe last page of the questionnaire was completed after
debriefing. It is apparent from the results that the presence or absence
of alcohol in the "cocktail" was easily established by the subjects, and
therefore that part of the study was not blinded. However, only two of
the nine were accurate in distinguishing the two dosages. Subjects'
accuracy in determining when they received diazepam versus placebo was
only about half accurate, and only one subject could distinguish the low
from the high dose accurately. Excess noise from conversation, laughing,
joking, etc. during the alcohol days had some influences upon the behav-
ioral testing according to this questionnaire.

NEUROLOGICAL

Test conditions that varied during the Romberg and heel-to-toe equilibrium
testing just after entry and before exit from the controlled-environment
chamber were the PCE concentration and the presence or absence of diazepam.
Any ethanol effect would have been mitigated by the four-hour time

period between alcohol consumption and chamber exit. Because diazepam
dosage was on a more continuous basis over a week's period, any differences

17
''between the entry and exit performance would most likely have been due
to PCE.

Table XXXVI also lists the deviations that occurred in EEG testing.
Unfortunately, the computer program that recorded the EEG epochs on tape
was unavailable until the third day of Week 4. However, with the repeat
of Week 3, all types of exposure combinations were eventually put on
tape and therefore were studied. The accidental blinking of a strobe
light in the EEG room during days 3 and 4 of Week 8 may have inadvert-
ently affected some subjects EEGs during those days (placebo plus 100
ppm and plus 25 ppm PCE).

PHYSIOLOGICAL

Pulse rates were recorded in the resting state three times daily, and
three times during the 30 min of daily exercise. Bicycle ergometer
loads were set individually to cause an approximate increase of 30 beats
per min during the exercise period. Loads had to be adjusted at least
once for all subjects as their physical performance usually improved
during the study.

SUBJECTIVE

Each subject completed a Lorr-McNair mood adjective checklist in the
midst of the behavioral testing on a daily basis. As noted under Method-
ology, the 56 adjectives or phrases to assess mood were divided into
categories for analysis to indicate depression, carefree, friendliness,
hostility, anxiety, cognitive gain, guilty-ashamed, fatigued, and miscel-
laneous (see Table XXXVII). Four direction phrases were also included
for a total of 60 multiple-choice questions. A visual assessment of the
answers to the four direction-type questions showed that all subjects

had no problem on any day with following these simple directions.

Two of the nine categories of mood need some explanation. As seen in
Table XXXVII, the cognitive gain category included the terms confused,
able to think clearly, forgetful, able to concentrate, and alert.
Obviously some of these terms are opposite in effect and therefore a
change in score was difficult to assess. The miscellaneous category
included nine mostly unrelated adjectives, again making scoring almost
meaningless. In all other categories, an increase in score could be
directly related to an increase of this particular mood.

Figures 4 through 12 relate the daily mean scores (+ SD) of each of the
nine groups of mood assessment to treatment. The straight lines describe
the trend of scores for zero exposure conditions and the outer lines the
95% confidence limits of the zero exposure means. Unfortunately,there
was a wide range of responses for all categories,with no change easily
relatable to exposure condition. This was confirmed with the trend
adjusted t-test where no significant differences (p < 0.05) from zero
exposure scores were found for any treatments in any categories. The
analysis of variance approach, using individual differences from predicted
values in the paired t-test to compare treatments, also revealed a low
level of significant changes in mood with treatment. On high level

18
''alcohol days, scores on the cognitive gain decreased (p < 0.005) and the
miscellaneous category increased (p < 0.05). Unfortunately, neither of
these two categories included a well-defined mood. Diazepam treatment
also resulted in a significant increase (p < 0.005) in score of the
miscellaneous category. During the diazepam treatment weeks, the analysis
of variance revealed a significant increase (p < 0.025) in friendliness
due to PCE, and an interactive effect of PCE and diazepam to significantly
decrease (p < 0.025) friendliness.

Subjects noted subjective symptoms on the subjective reponse forms eight
times per exposure day, and PCE odor perception seven times. The number
of subjects per day who noted a given symptom or perceived the odor of
PCE (responders), and the total number of times each were noted per day
(responses), were totaled for each different type of exposure. Because
there were often different numbers of subjects and, therefore, different
numbers of subjective response forms returned under different conditions,
total numbers of responders and responses were divided by the number of
forms returned in order to give a rate per subject report. These rates
are listed by type of response as "incidence" and "persistence," responders
and responses, respectively, in Tables XXXVIII and XXXIX. There was no
suggestion of a trend to a greater rate of any symptom when exposures to
increasing concentrations of PCE alone took place. However, as expected,
the PCE odor perceived became stronger and persisted longer as the PCE
concentration increased. Table XXXVIII shows the results for the addition
of placebo, 6 mg, and 10 mg of diazepam to each level of PCE. Again
there seems to be no dose-response relationship regarding untoward
symptoms, and only the odor perception increases with increasing PCE
concentration. Table XXXIX demonstrates similar responses for addition
of alcohol to the PCE exposures. It appears that the alcohol may have
actually decreased the number of symptoms in some areas. As a whole, it
can be concluded that, despite the increase in PCE odor perception with
increasing PCE concentration, PCE, diazepam, alcohol, or the combinations
of these at the levels studied had no discernible effect upon the
subjective symptoms of the subjects.

The staff assessments of the subjects' mood and behavior while they were
in the controlled-environment chamber are summarized in Tables XL and
XLI. Five staff members who worked with the subjects, but were not
informed of the PCE concentrations or the drug and alcohol dosages,
completed the mood and behavior assessment daily. The scales between
opposite types of behavior ranged from +5 through 0 to -5 (see Appendix
VI). The means for each condition are listed in the tables. PCE
concentration alone had no effect on these assessments, while the higher
dose of alcohol was assessed to increase the subjects' happy, at ease,
friendly, carefree, full of pep, giddy, talkative, active, and staggering
images, and the higher dose of diazepam decreased the subjects' alert,
concentration (able to think clearly), happy, full of pep, talkative and
active images,as assessed by the staff.

19
''RESULTS OF BEHAVIORAL AND NEUROLOGICAL TESTING
BEHAVIORAL MEASUREMENTS
Michigan Eye-Hand Coordination Test

The Michigan eye-hand coordination test required the subjects to follow
a weaving maze-like path with an electronic recording stylus. At each
of the 119 points in the path, changing direction at each point, the
stylus was fully inserted to the bottom of the hole. The response
measured at each trial was the total elapsed time in seconds required
for the completion of the entire path tracing. The final score was the
total of four path tracings. Thus, a higher score indicated a slower
response time. This test incorporated many of the eye-hand coordination
movements encountered in manual work tasks requiring hand and arm dexter-
ity. Each subject performed the test twice daily, once within 60 min of
entry into the chamber and prior to exercise and dosing (labeled AM),
and again 1-1/2 hr later after exercise and dosing (labeled PM). The
two daily test scores were analyzed separately.

Figure 13 displays the mean scores (+ one SD) for both AM and PM tests.
Even though the subjects were trained before the exposure sequence was
initiated, the general improvement in performance is quite noticeable,
especially during the first few weeks. Inspection of Figure 13 reveals
that the higher level of alcohol (ca 1.50 ml/kg) produced the greatest
variation in the PM scores.

Analysis of the data from weeks pertaining to PCE exposure and alcohol
yielded the following multiple regression equations:

AM score 47.67 - 0.1199 D + 0.0016 P - 0.1196 A - 0.0091 (P x A) + subject effects

45.90 - 0.1089 D + 0.0037 P + 1.7529 A - 0.0023 (P x A) + subject effects

Hi]

PM score

Where: D = day number (0 through 75)
level of PCE (0, 25, or 100 ppm)
level of Alcohol (0, 0.75, or 1.5 ml/kg)

u

Analysis of variance summaries for these two multiple regressions are
given in Tables XLII and XLIII. Results indicate the highly significant
improvement trend (linear day effect). Alcohol manifested its signif-
icant effect in the PM scores. PCE showed no significant (linear)
effect and no significant interaction effect with alcohol. Trend ad-
justed t-tests (Table XLIV), which were designed to correct for indi-
vidual improvement in scores, showed that PM scores yielded significant
increases (decrements) in test completion time on two days (56 and 58).
Fortuitously, these t-tests showed a significant improvement in AM score

20
''during the first week in which alcohol was used (0.75 ml/kg). This is
not an alcohol effect because it was administered after the test. The
improvements could have been due to some subjects performing well in
anticipation of their alcohol "cocktail" and/or a reflection of the
general point in the study where further baseline improvement subsided
and, since overall improvement was accounted for by a straight-line
relationship for the entire study, one would expect deviations from the
assumed linear zero-exposure trend.

Subparts of the study encompassing PCE exposure and diazepam combinations
produced the following multiple regression equations:

AM score = 47.91 - 0.1322 D - 0.0041 P + 0.0861 V + 0.9428 (P x V) + subject effects
46.62 - 0.1257 D - 0.0024 P + 0.0874 V - 0.0010 (P x V) + subject effects

PM score

day number (0 through 75)
leve’ of PCE (0, 25, or 100 ppm)
level of diazepam (0, placebo = 0, 6 or 10 mg/day)

Where: D

The analysis of variance for each multiple regression is given in Tables
XLV and XLVI. The linear day trend was the only significant effect.

PCE and the interaction with diazepam showed no significant effects.
Analysis of all days excluding alcohol (0.75 and 1.5) and diazepam (6
and 10) yielded multiple regression equations:

AM score = 47.59 - 0.1259 D - 0.0055 P + subject effects
PM score = 46.28 - 0.1196 D - 0.0032 P + subject effects

Corresponding analysis of variance tables are not presented, but as
indicated by the underlined effects, only the linear day trend was
significant. The AM and PM scores for these no ethanol:no diazepam days
correlated quite highly (r = 0.9324), agreeing with the previous report
by Pook (1967).

Flanagan Coordination Test

The Flanagan coordination test required the subjects to draw with a
pencil a continuous spiral path between well-marked spiral boundaries.
Forty sec were allowed for completion of each of four scored trials and
the test score was a function of the greatest distance obtained and the
number of spiral borders that were touched (adds negatively to the final
score). The scoring was standardized to a 0 to 100 point scale, with
100 points signifying a perfect score. Scores above 100 were impossible
and scores of 100 were rarely obtained. However, scores below zero can
be observed when subjects are intoxicated (alcohol). Past experience
has shown that individuals show marked differences in the Flanagan
coordination test. Improvement in score was generally achieved over a
period of weeks, particularly for subjects with low initial scores and
less frequently for subjects with high initial scores.

21
''The graph in Figure 14 shows the daily Flanagan coordination mean
responses for the entire study period. The average trend line shown was
obtained only from the zero exposure days of the study (open circles on
graph). The trend line reveals only slight improvement for the group of
nine subjects. The boundary about the line depicts a region that can be
expected to contain about 95% of future coordination score means if
experimental conditions remain at zero (no PCE, diazepam, or alcohol).
Obvious deviations from the control situation occurred during weeks when
subjects received either low alcohol or high alcohol. The trend ad-
justed t-tests given in Table XLIV show that significant deviations
obtained during low alcohol, high alcohol and high PCE, high diazepam,
high diazepam and high PCE, and low diazepam and high PCE. All of these
deviations resulted in an average reduction in the coordination score.
Multiple linear regression analysis performed on zero-exposure days and
alcohol exposure weeks yielded multiple regression equations:

C = 81.13 + 0.0456 D - 0.0418 P - 7.0537 A + subject effects
C = 80.83 + 0.0453 D - 0.0332 P - 6.2909 A - 0.01848 (P x A) + subject effects

Where: = average coordination score

Cc
D = day number (0 through 75)

P = level of PCE (0, 25, or 100 ppm)

A = level of Alcohol (0, 0.75, or 1.5 ml/kg)

Underlined coefficients in the above equations correspond to significant
effects as determined by the analysis of variance for the multiple
regression(s) (Table XLVII). The effect of PCE and alcohol is exhibited
by an augmented drop in average score, particularly noticeable on days

58 and 60 (Figure 14). However, the interaction effect was not statisti-
cally significant (in the equation above). Alcohol had an extremely
significant effect and this is obvious in Figure 14 and in Table XLVII.
By focusing only on this subset of the study, the linear effect of PCE
indicated a drop in coordination score of three to four units per 100

ppm PCE. A similar effect of PCE was not entirely confirmed for days
when alcohol and/or diazepam (including placebo) was absent, but inclusion
of placebo (diazepam) days to other zero days yielded a statistically
significant linear PCE effect. The corresponding multiple regression
equation for the drug non-exposure days are:

C = 79.79 + 0.0482 D - 0.0191 P + subject effects
C = 81.36 + 0.0364 D —- 0.0387 P + subject effects (placebo days included)

Analysis of PCE and diazepam exposure revealed similar results. Multi-
ple regression equations reflecting effects of days, PCE and diazepam
are:

22
''80.10 + 0.0413 D - 0.0253 P - 0.2265 V + subject effects
80.05 + 0.0413 D - 0.0241 P - 0.2095 V - 0.00042 (P x V) + subject effects

"

Where: average Flanagan coordination score

day number

level of PCE (ppm)

<~€6UtUCUUOUCUCU
"

= level of diazepam (mg/day)

Table XLVIII gives the corresponding analysis of variance results to
multiple regressions. The effect of diazepam was not statistically
significant, the interaction of PCE and diazepam (linear interaction)

was not statistically significant, and the linear effect of PCE and the
linear day trend showed statistical significance only in the first
equation above. These results were derived from an analysis that com-
pared exposure factors with smaller measures of random variation (the
Residual Mean Square of Table XLVIII is smaller than the Residual Mean
Square of Table XLVII) and this accounts for the day trend being declared
significant.

The effect of PCE was in the neighborhood of a two to four unit reduction
for a 100 ppm exposure to PCE. This effect was not consistently statisti-
cally significant for all subparts of the experiment.

Rotary Pursuit Test

The rotary pursuit test required the subjects to maneuver a hand-held
electronic recording stylus in a circular pattern so that it "pursued" a
one-inch square light that revolved in a 30-cm diameter circle. The
rotation of the light for each of four successive trials was fixed at
constant speeds of 15, 30, 45, and 60 rpm, with each trial lasting 45
sec. Variables recorded that characterized each subject's performance
were (1) the time off target, in seconds, and (2) the number of errors
or the number of times the stylus moved off and onto the target while
tracking it. This was an eye-hand coordination test similar to the
Flanagan coordination test in the sense that circular motion was involved.
However, it differed from the Flanagan in several respects, namely (1)
the circular pattern was much larger than the series of concentric
spirals of the Flanagan, (2) the speed of the rotation was fixed for
each trial, and (3) the rotary pursuit was administered in a standing
rather than a sitting position as in the Flanagan.

Analysis of the rotary pursuit data revealed that the time off target
and the number of errors provided nearly equivalent information with
respect to the influence of PCE, alcohol, and diazepam. Figures 15, 16,
17, and 18 depict the daily mean results for each rotation speed. As
rotation velocity increased, the time off target also increased; and as
the study progressed, the subjects exhibited improved trends in tracking
ability at each of the four speeds.

The effects of PCE and alcohol are illustrated in the following multiple
regression equations:

23
''Ty. = 1.47 - 0.00321 D + 0.00132 P + 0.73159 A + 0.00021 (P x A) + subject effects
T39 = 7.86 - 0.04124 D - 0.00281 P + 2.9837 A + 0.00567 (P x A) + subject effects

Tys5 = 17.08 - 0.08345 D + 0.00548 P + 5.2654 A + 0.00836 (P x A) + subject effects
T 66 = 26.36 - 0.07443 D - 0.01267 P + 3.6921 A + 0.02129 (P x A) + subject effects

Where: time off target at speed s (rpm)

level of alcohol (0, 0.75, or 1.5 ml/kg)
= level of PCE (0, 25, or 100 ppm)

tl

iF
s
D = day number (from 1 to 75)
A
P

Analysis of variance tables that correspond to the above regression
equations are given in Tables XLIX, L, LI, and LII. Results indicated

a clear day trend that exhibited improvement in performance. Alcohol
effects significantly increased the time off target at all four rotation
speeds. However, the effect of PCE was not significant at any of the
four speeds, and moreover, the alternating signs of the PCE coefficients
Suggests inconsistent directional effects. The linear by linear inter-
action of PCE and alcohol was also non-significant,except at 60 rpm
trials,where it was significant at the p = 0.05 level. The effect of
alcohol is quite obvious in Figures 15, 16, 17, and 18. It is note-
worthy that the number of errors also showed similar deviations from
expected responses during zero exposure conditions,except at the fastest
rotation speed, where the number of errors is lower than expected be-
cause of the large amount of time spent off the target during high
alcohol conditions. The trend adjusted t-tests in Table XLIV demon-
strate that the high level alcohol week resulted in the most consistent
significant deviations from the expected response of zero exposures.
This occurred for all four rotation speeds and also for the number of
errors at 15 and 30 rpm. The low alcohol week showed essentially no
significant deviations from the expected trend line (Figures 15, 16, 17,
18, and Table XLIV).

Multiple regression equations that display the effects of diazepam, PCE,
and day trends in concert are:

"

T 1.45 - 0.00233 D - 0.00082 P + 0.07149 V - 0.00007 (P x V) + subject effects
T,, = 7.33 - 0.03641 D —- 0.00463 P + 0.06806 V + 0.00093 (P x V) + subject effects
T
T

16.65 - 0.07524 D + 0.00130 P + 0.21287 V - 0.00053 (P x V) + subject effects
25.61 - 0.06754 D - 0.00968 P + 0.23283 V + 0.00053 (P x V) + subject effects

Where: V = level of diazepam (0, 6, or 10 mg/day)

Analysis of variance tables that correspond to the above equations are
found in Tables LIII, LIV, LV, and LVI. As with the alcohol subset
analysis, the diazepam and PCE analysis showed no significant PCE effect
and no significant linear by linear interaction effect of PCE and diaze-
pam. This conclusion was made for each of the four rotation speeds.

The day trend is significant at speeds of 30, 45, and 60 rpm, and the
effect of diazepam is significant at 15, 45, and 60 rpm, in the regres-
sions shown above. If the 30 rpm speed is analyzed ignoring the inter-
action term, the resulting multiple regression equation becomes:

24
''T39 = 7.23 - 0.03652 D - 0.00182 P + 0.10602 V + subject effects

Now the diazepam effect reappears with a larger coefficient and also
tests to be statistically significant (p < 0.005). (The corresponding
analysis of variance is not presented.) The diazepam effect indicates
that time off target increased as the dose of diazepam was increased.
Trend adjusted t-tests show no significant deviations for the 6 mg dose
of diazepam during Week 2, and a few significant deviations at the 30
rpm speed at the identical dose level during Week 11 (see Table XLIV).
The high dose diazepam week, Week 7, showed essentially no significant
deviations from the expected zero exposure trend line. Oddly though,
the placebo diazepam exposure (Week 4) produced significant deviations
from the expected responses for the 15, 30, and 45 rpm speeds on no PCE
and PCE days. Some deviations from control levels would be expected.

The summary of the multiple regression analyses of the rotary pursuit
data is as follows: (1) PCE did not exhibit a statistically significant
effect for time off target, (2) its interaction with alcohol or diazepam
also showed no statistical significance, and (3) alcohol and diazepam
alone each produced significant effects that increased the time off
target.

NEUROLOGICAL MEASUREMENTS

Only once during the three-month study did a subject perform abnormally
on the equilibrium test. This occurred on a high-dose diazepam combined
with 100 ppm PCE day in the test given just prior to leaving the chamber.
Subject 95 could not perform a normal heel-to-toe walk with eyes closed.
Because all other subjects performed the dual test (Romberg and heel-to-
toe) normally, this single abnormal result of 18 tests performed under
these conditions was considered as spurious.

The subjects were divided into Groups A and B as explained earlier,
Group A undergoing electroencephalographic tests on ethanol, placebo,
and certain control days while Group B underwent EEG testing on diaze-
pam, alternate placebo, and alternate control days. Figures 19 through
24 and 25 through 30 are plots of each subjects' EEG power spectra which
are representative of those generated during each treatment condition
for the PCE-ethanol (Group A) and PCE-diazepam (Group B) subject groups,
respectively. Table LVII presents the results of the analysis of variance
for shifts in the dominant frequency from each of the four leads over
all the treatment conditions. Tables LVIII and LIX present the results
of the analysis of variance for changes in the percent relative activity
in the a, 8, 6 and 6 bands for each of the four leads over all the
treatment conditions.

Visual comparison of the three power spectra derived from subjects in
Group A (Figures 19, 20, and 23) showed that subjects 117 and 327 had no
shifts in the distribution during treatment days that did not also occur
on control days. Subject 95, however, did show increased a activity in
lead 3 (F7-F8) and increased § activity in lead 2 (F8-02) after ingesting

25
''alcohol during Week 5, but this did not occur consistently over all the
days of that week. Neither did it occur at the higher level of alcohol
ingestion. The peak that appears in these power spectra at 4 Hz is an
artifact of 60 Hz noise. The noise appeared at 4 Hz due to the sampling
rate, and while it appeared in some of the spectra, it was not visible
in the EEG tracings themselves.

The one-way analysis of variance for the three subjects in Group A
showed no significant effects on the dominant frequency for any subject
(Table LVII), but did show an effect in the percent relative amount of
activity in the a band for subject 95 (Table LVIII). This effect was a
significant decrease in the relative amount of a activity in lead 2 (F8-

02) during the high alcohol alone, and the high PCE plus placebo, treat-
ment days.

Visual comparison of the power spectra of the six subjects in Group B
(Figures 25 through 30) show no consistent changes between treatment
conditions. The one-way analysis of variance tests showed several
significant shifts in the dominant frequency in one of six subjects
(Table LVII) and percent relative activity of bands from four leads
(Table LIX) in four of the six subjects. These shifts are correlated
with the corresponding treatment conditions in Table LX. Although no
consistent pattern emerged, a majority of them occurred on a combined
PCE exposure and diazepam ingestion day, and was elicited as increased
B activity. Only one of these (subject 333, increased 8 activity in
lead 1) can be attributed to a deviation in conditions, as this oc-
curred on the day a light inadvertently blinked in the darkened testing
room.

26
''DISCUSSION

The discussion of the voluminous bank of data obtained in this study is
divided into four main parts: (1) the effect of perchloroethylene (PCE)
alone, (2) the effect of alcohol alone and in combination with PCE, (3)
the effect of diazepam alone and in combination with PCE, and (4) the
comparison of behavioral tests.

A comprehensive study on the total effect of repeated exposure to PCE
alone has been reported from this laboratory (Stewart, et al., 1974).
The following conclusions were advanced in that final report:

1. Repeated daily exposures to PCE result in a tachyphylactic
type of response regarding subjective feelings and odor detection.
Therefore, both of these parameters are unreliable measures of ex-
posure concentration.

2. There is considerable individual difference in subjective
response to PCE vapor exposures.

3. EEG analyses indicate that the preliminary signs of nar-
cosis are present in most subjects exposed to 100 ppm PCE for 7-1/2
hours per day.

4. Impairment of coordination may occur at 150 ppm exposure
for 7-1/2 hours.

5. Because there is very little metabolism of PCE by humans,
the CNS response is probably due to the PCE itself.

6. Analysis of the chemical in the postexposure exnired
breath provides an excellent tool for estimating the magnitude of
the body burden of PCE.

7. Physical activity (exercise) during exposure to PCE drama-
tically increases the body burden of the chemical. Therefore, the
time-weighted average concentration to which a male or female human
is exposed may not reflect the true body burden attained by that
individual.

8. Postexposure levels of the chemical in the breath are an
accurate reflection of the body burden and thus provide a "biologic
threshold limit value" for worker exposure to this chemical.

None of the above conclusions need be abrogated from the results of the
present study; however, several require further clarification. None of
the twelve subjects exposed to PCE in the present study was unusually
susceptible to PCE vapors as related to objective tests. However, as in
the previous study, one subject reported many more subjective symptoms
than all others. This subject accounted for 1/3 of the incidence of
headache and 2/3 of the nausea reported by the nine subjects who completed

27
''the study. This subject also reported ENT irritation on all but 8 of
the 55 exposure days. Upon analysis of the times of reporting these
subjective symptoms, it was found that there was no relationship to PCE
vapor exposure; in fact, the incidence decreased somewhat when the 100
ppm PCE exposure concentrations were compared to non-PCE exposures.

The preliminary signs of narcosis, as indicated by EEG changes found by
subjective review of tracings in most subjects exposed to 100 ppm PCE
for 7-1/2 hr inthe previous study, were not found with PCE‘alone in the
present study. In this study, the EEG power spectra analyzed were
obtained by averaging six power spectra generated from four 4-sec epochs
for a total of 96 sec. This should have been sufficient time to demons-
trate any significant changes in the spectra had they occurred. The
conditions and subjects for the two studies were different, therefore,
one cannot assume that either study was in error regarding EEG changes
from exposure to 100 ppm PCE. However, it appears that EEG testing is
an unreliable test for the early detection of narcosis due to PCE expo-
sure,

Of great interest is the fact that PCE alone caused a significant
decrement in the Flanagan coordination scores on some of the 100-ppm
exposure days. This confirms the finding in the previous study wherein
the group of male subjects exposed to 150 ppm for 7-1/2 hr per day had a
significant decrement in performance on the same test. There were no
significant decrements in performance in the Michigan eye-hand or rotary
pursuit tests due to PCE alone.

The assessment of effects of PCE upon any change from control in mood of
the subjects during exposure to 100 ppm revealed almost no effect either
by the subjects own assessment or by the assessment of staff personnel.
Analysis of variance did reveal that during the diazepam treatment
weeks, PCE exposure caused the subjects to feel more friendly than
expected. In looking at the weekly data, this appears to have been due
to a "more friendly" attitude during Week 3 when the subjects may have
first felt "better acquainted."

Analysis of the blood and breath levels for PCE after 30 min of exercise
confirmed the rather dramatic effect that exercise confers upon body
burden of PCE. The previous study had indicated that an increase would
occur and this was confirmed. The similarities in blood and breath PCE
levels between male and female subjects found in this study are different
from the previous study. However, it was theorized that the lower
levels found in female subjects previously could have been due to the
fact that they did not exercise during the exposures, while male subjects
exercised, though minimally.

e
Post exposure breath analysis at 30 min revealed that 5-1/2 hr of
exposure to PCE vapor resulted in a mean breath level of 17.6 + 3.3 ppm
(n = 64) PCE for all subjects exposed to PCE alone or PCE and placebo.
This compares favorably to the previous study of male subjects where a
similar exposure to PCE vapor for 7-12 hr resulted in a mean PCE breath

28
''concentration of 26.5 + 3.2 ppm (n = 40) 30 min post exposure. These
results further confirm that "post exposure expired breath provides an
excellent tool for estimating the magnitude of the body burden of PCE."

In summary, we found no effects from the exposure of twelve human
subjects to PCE vapor at 25 or 100 ppm concentration for 5-1/2 hr that
were either unpredictable or unexpected.

Turning to the effects of alcohol, it has been impossible to review all
of the myriad of previous publications on the behavioral effects of
alcohol. In our own laboratory, we have found in previous studies that
blood alcohol levels of > 50 mg/dl caused a significant decrement in
performance scores of the Flanagan coordination test. Moskowitz and
Sharma (1974) reported a decrement in the dual-attention tasks test, if
the central white light was blinking, with blood alcohol levels of
0.06%. (Breathalyzer test. This is equivalent to ca. 60 mg/dl.) Using
the rotary pursuit test, Kalant, et al., (1975) found a decrement in
performance, measured by time on target at 30 rpm for 1 min, in both
male and female subjects when blood levels reached 50 to 70 mg/dl.

These levels were similar to our high dose levels. Sidell and Pless
(1971) found the "greatest decrement in performance was on the test
requiring hand-eye coordination; lesser decrements were produced on
tests of cognitive ability" when subjects ingested from 0.5 to 2.0 ml
ethanol/kg body weight. Serial blood alcohol levels revealed a rather
level concentration from 0.5 to 2 hr post dosing when the alcohol was
consumed as a juice "cocktail" over a half-hour period. At the blood
levels equivalent to our low dose, the blood alcohol level was reduced
to almost zero at 4 hr post dosing, while the level equivalent to our
high dose level neared zero at 6 hr. Jones and Vega (1972) showed that
after alcohol consumption, which was slightly higher than our high dose,
students demonstrated a poorer performance on cognitive testing only
when the blood alcohol concentration was rising. While the concentration
was decreasing (about 2 hr post dosing), performance was identical to
placebo controls. From these results, it would appear that all of our
behavioral testing was carried out during the correct time period post
dosing to observe maximum decrement in performance. However, the EEG
spectra were obtained on the descending limb of the blood alcohol con-
centration curve at a time when the expected alcohol effect was past its
maximum.

The mood tests completed by the subjects themselves did not confirm the
staff assessment that alcohol increased the subjects' general "euphoric"
mood. In fact, the consumption of alcohol had a significant effect on
only two categories of the subjects' own assessment of their mood. The
scores in the cognitive gain category (which included the adjectives
confused, able to think clearly, forgetful, able to concentrate, and
alert) were significantly lowered due to alcohol, while those for the
miscellaneous category (suspicious, feel sexy, need a cigarette, need a
drink, taken advantage of, hungry, headache, stomach upset, and trouble
seeing) were significantly increased. Although these changes in "mood"

29
''could be expected, the subjects did not see themselves as more carefree
and friendly as the staff assessed them. In addition, there was no
interactive effect between PCE and alcohol on the subjects' own assessment
of their mood.

The Michigan eye-hand coordination test was the only test in which all
subjects participated in daily both prior to and after consuming alcohol
or a dose of diazepam. Alcohol alone at 1.5 ml/kg had a significant
effect, resulting in an increased score (a slowing down), upon the
performance of this coordination test. There was no significant inter-
action with PCE, even at the 100 ppm exposure concentration. A similar
picture was obtained with the Flanagan coordination test. Here, a
significant reduction in score, equivalent to a poorer performance, was
observed with both low and high alcohol alone. Although high PCE also
caused an occasionally significant decrement in performance, the inter-
action effect between alcohol and PCE was not statistically significant
due to the extremely significant effect of the alcohol. Alcohol alone
also had a significant detrimental effect upon performance of the rotary
pursuit test, both in time off target and in number of errors, during
the high dose week. However, this was not true during the low dose
week, nor was there a statistically significant interaction with PCE.
Moskowitz (1974) has observed significant effects of alcohol at low
dosage levels on the dual-attention tasks test where divided attention
to both signal detection and recall of simultaneously presented digits
were required.

Ethanol consumption alone, or with simultaneous exposure to PCE, had
little effect on the power spectra generated from the EEGs. One of the
three subjects who underwent EEG testing during the ethanol dosing weeks
did show significantly increased a activity which would correlate with
a more relaxed feeling. It is not surprising that an alcohol effect
upon the EEG was not uncovered because the EEG testing was carried out
either before the consumption of the "cocktails" or several hours after
when blood alcohol levels were probably low or undetectable (Jones and
Vega, 1972).

Before leaving the subject of alcohol effects, it must be mentioned that
PCE at 25 ppm seemed to have a positive effect on the blood alcohol
concentration, particularly at the lower dose level. The average blood
alcohol level of eight subjects was 50.7 + 8.6 mg/dl during the low
alcohol, low PCE day, while it was significantly lower, 40.1 + 12.5
mg/dl on the two low alcohol, zero PCE days. A similar relationship was
demonstrated during the high alcohol week, although the difference was
not significant (66.1 + 17.7 vs 58.5 + 13.2). It may also be recalled
that alcohol (both weeks combined) had a statistically significant
effect on the blood level of PCE during low PCE (25 ppm) exposure days
(Table XXXV). The reason for these increases is uncertain, although
they may have simply been due to the physical effects of solubility.
However, one would have expected them to also occur at the high dose
levels.

Kleinknecht and Donaldson (1975) have recently reviewed the effects of
diazepam on cognitive and psychomotor performance. From this review, it

30
''is evident that our dosage regimens of 6 mg or 10 mg per day were on the
threshold of impaired performance in many of the various tasks assessed.
The review divided the tasks into six major groupings: reflex speed;
critical flicker fusion threshold; attention and vigilance; decision
making; learning and memory; and psychomotor performance. At 6 mg per
day or less, it seems that only the critical flicker fusion threshold

was definitively impaired, while reflex speed was unimpaired at doses up
to 15 mg/day. In one of the papers, the reviewers report that 10 mg of
diazepam administered over a 14-hr period had no effect on the pursuit
rotor test. Combination effects of diazepam and alcohol taken together
were reported as additive, or occasionally potentiating, although "typi-
cally the effects are not dramatic."

A factor that often was not taken into account in the previous studies
was the cumulative dose effect. In our studies, diazepam blood levels
were generally lowest on Monday, and generally increased during the

week, despite the beginning of dosing on the previous Friday

evening. Hillstead, Hansen, and Melsom (1974) also reported a cumulation
of diazepam, and metabolite, in blood over a period of one week. However,
the clinical effects, evaluated somewhat subjectively and classified on

a zero to four scale, were not changed greatly during the full two weeks
of dosing at 15 mg/day (5 mg t.i.d.). We found a lower mean blood level
after 10 mg/day dosage during Week 7 than during Week 3 when the dosage
was 6 mg/day. A repeat of the 6 mg/day dosage regime during Week 11
yielded significantly lower mean blood levels. Blood sampling was
carried out at the same time period after capsule ingestion all three
weeks. The lowered diazepam blood levels we found during the second and
third week of dosing corroborate the work of Sellman, et al., (1975) and
indicate that metabolic enzyme induction reduced the blood levels of
diazepam. The results of the rotary pursuit testing indicate that this
reduction in blood level was not associated with a decrement in performance.

Diazepam alone or in combination with PCE had no significant effect upon
the performance of the Michigan eye-hand or the Flanagan coordination
tests in our studies. However, the drug alone had a significant effect
on the time -ff target, but no interaction effects with PCE, in the
rotary pursuit test. The EEG changes seen in this study almost all
occurred during a combination of PCE and diazepam. Interestingly, the
PCE plus diazepam changes were asymmetrical, generally occurring in only
one lead. Although an asymmetrical EEG change is unusual, it is in
agreement with the previous PCE study from this laboratory (Stewart, et
al., 1974) and the report of Hynek, Tosovsky, and Siisova (1975), who
related asymmetrical changes to right and left handedness. Contrary to
our previous study, the majority of changes seen in the present study
were increases in 8 activity as opposed to 6 activity. Montagu (1972)
has studied the effects of low doses of diazepam on the EEG of normal
subjects and reported decreased theta activity and increased beta activity
with eyes open. During the eyes shut testing,his subjects demonstrated
typical light sleep and drowsiness in their EEG patterns.

Diazepam also had a visible effect upon the staff's assessment of mood
of the subjects. The staff evaluation of the subjects' mood and behavior

resulted in decreased alertness, concentration, happiness, peppiness,

31
''giddiness, talkativeness, and activity, all especially noticeable during
the high dose week. However, the subjects' themselves revealed only a
significant decrease in the miscellaneous mood category attributable to
diazepam dosing. This category included the adjectives suspicious, feel
sexy, need a cigarette, need a drink, taken advantage of, hungry, head-
ache, stomach upset, and trouble seeing. There was also a significant
interactive effect with PCE during the diazepam dosing weeks resulting
in a mood of less friendliness. Included in this category were the
adjectives good natured, friendly, kind, warmhearted, pleasant, and
considerate. From this result, we can assume that the subjects assessed
themselves to be less friendly during the diazepam and high PCE exposure
days.

The effect on each behavioral test for which the data has been analyzed
demonstrates that each test provided slightly different results. How-
ever, in none of the behavioral tests was there an interaction effect
between PCE and alcohol or PCE and diazepam. The general increases in
the average scores of the Michigan eye-hand coordination test were:

 

COMMENT

EXPOSURE CONDITION
PCE, 100 ppm
Diazepam, 10 mg/day

Alcohol, 1.5 ml/kg

The general reduction
test were:

EXPOSURE CONDITION
PCE, 100 ppm
Diazepam, 10 mg/day

Alcohol, 1.5 ml/kg

SCORE INCREASE
0.25 to 0.50 sec
0.86 sec

3.1 sec

in the average scores of

SCORE REDUCTION
2 to 4 units
2 units

9 to 10 units

not significant
not significant

significant

the Flanagan coordination

COMMENT
occasionally significant
not significant

highly significant

The average changes in time off target in the rotary pursuit test due to
exposure conditions were:

EFFECT ON TIME OFF TARGET (SECONDS)

 

Exposure

Condition 15 rpm 30 rpm 45 rpm 60 rpm Comment

PCE, all not
100 ppm -08 to +.3 +28 to .46 +.1 to+.5 -9 to -1.2 significant

Diazepan, all significant
10 mg/day +0.7 +1.1 +2.1 +23 decrements

Alcohol, all significant
1.5 ml/kg +1.1 +425 +7.9 +55 decrements

74 Days of all significant
Testing, -.2 to -.4 -2.7 to -5.0 -5.6 to -8.0 -5.1 to -6.4 improvements

32
''Comparison of the results from these three behavioral tests show that
the high dose of alcohol had a significant detrimental effect on perfor-
mance in all three tests, the high dose of diazepam had a detrimental
effect on performance of only the rotary pursuit test, and high PCE had
an occasional detrimental effect only on the Flanagan coordination test.

The correlation of performances on the rotary pursuit test at four
speeds to the other two coordination tests during 21 days when complete
data for all nine subjects was available resulted in the following
levels of correlation:

 

TEST 15 rpm 30 rpm 45 rpm 60 rpm
low middle high low middle high low middle high low middle high
Flanagan
coordination -.77 -.53 +.15 -.90 -.60 -.17 -.81 -.62 +.01 -.66 -.45 +.29

Michigan eye-
hand, AM -.37 +.08 +.49 -.29 +.25 +.53 -.40 +.29 +.73 +.01 +.43 +.77

Michigan eye-
hand, PM -.32 +.11 +.83  -.26 +.31 +.78 -.20 +.28 +.86 -.01 +.54 +.88

From these correlations it can be concluded that the rotary pursuit test
at all speeds is moderately correlated with the Flanagan coordination
test while the Michigan eye-hand coordination test, both AM and PM,
correlate best with the rotary pursuit test at high speeds and poorly at
low speeds. These results, together with the detrimental differences
already noted, suggest that these coordination tests measure similar but
not identical tasks.

33
''CONCLUSIONS

A comprehensive study of the behavioral and neurological effects of
perchloroethylene (tetrachloroethylene) exposure alone at OSHA standard
concentrations, and in combination with low doses of diazepam or alcohol,
has been carried out. The result of data analysis from one behavioral
test is not yet available. However, the results of all other behavioral
testing lead us to conclude that perchloroethylene at its present
standard of 100 ppm had no consistent,significant effect upon the perfor-
mance of four behavioral tests, and the addition of alcohol or diazepam
at relatively low levels added no significant decrement to performance
over and above that imposed by the alcohol or diazepam itself, There
was a non-consistent significant detrimental effect of perchloroethylene
alone in the performance of the Flanagan coordination test. However,

any additive effect or interaction with alcohol was obscured by the
highly significant alcohol effect upon the performance of this test.
There was no additive effect by diazepam addition to the PCE exposure,
Analysis of neurological data revealed a significant but inconsistent
increase in the beta activity of the EEG during combined perchloroethylene
exposure and diazepam dosing. We interpret this increased beta activity
to be due primarily to the diazepam, although it did not appear consis-—
tently with diazepam alone. However, diazepam alone has been reported

to have this effect, whereas, perchloroethylene alone has not.

At the levels of dosing studied, there was no exacerbation of the deleter-
ious behavioral and/or neurological effects of either alcohol or diazepam
when perchloroethylene was added to the exposure, However, the results
emphasize the hazard involved with drinking alcohol during any work
situation, as decrements in coordination were found at blood alcohol
levels below those generally considered to be legally drunk (100 mg %).
Diazepam, at the low dosages generally prescribed for outpatients,

caused a significant decrement in only one of three coordination tests.
The EEG changes noted are therefore difficult to associate with any
projected increased work hazard from these low dosages, In summary,

the results from this laboratory study suggest that the degree of

hazard the workman presents to himself and others when the effect of

low doses of alcohol or diazepam are added to that of breathing OSHA
standard PCE vapor levels will be no greater than these attributable

to the alcohol or diazepam alone.

34
''REFERENCES

American Conference of Governmental Industrial Hygienists: Documentation
of the Threshold Limit Values for Substances in Workroom Air, Third
Edition, ACGIH, Cincinnati, 1971, pp. 201-202.

Baloh, R. W., A. W. Sill, W. E. Kumley, and V. Honrubia. 1976. Quanti-
tative measurement of saccade amplitude, duration and velocity. (Man-
uscript submitted for publication.)

Crow, E. L., F. A. Davis, and M. W. Marfield. 1960. Statistics Manual.
Dover Publications, Inc., N.Y. p. 134.

Davis, D. 1971. Mood changes in alcoholic subjects with programmed and
free-choice experimental drinking. pp. 496-618. In: N. K. Mello
and J. H. Mendelson, Ed. Recent Advances in Studies of Alcoholism.
U.S. Government Printing Office.

Garriott, J. C. 1975. Diazepam, Type C Procedure. pp. 121-123. In:
I. Sunshine, Ed. Methodology for Analytical Toxicology. CRC Press,
Cleveland, Ohio.

Hillstad, L., T. Hansen, and H. Melsom. 1974. Diazepam metabolism in
normal man II. Serum concentration and clinical effect after oral
administration and cumulation. Clin. Pharmacol. Ther. 16:485-489.

Hynek, K., J. Tosovsky and J. Susov4. 1975. Interhemispheral differences
in the effect of psychotropic drugs in EEG. Electroencephalogr. Clin.
Neurophysiol. (Proceedings). 39:440.

Jasper, H. H. 1958. The 10-20 electrode systems of the international
federation. EEG Clin. Neurophysiol. 10:371-375.

Jones, B. M., and A. Vega. 1972. Cognitive performance measured on
the ascending and descending limb of the blood alcohol curve. Psycho-
pharmacologia (Berl.). 23:99-114.

Kalant, H., A. E. LeBlanc, A. Wilson, and S. Homatidis. 1975. Sensori-
motor and physiological effects of various alcoholic beverages. Canad.
Med. Assoc. J. 112:953-958.

Kleinknecht, R. A., and D. Donaldson. 1975. A review of the effects of

diazepam on cognitive and psychomotor performance. J. Nerv. Ment. Dis.
161: 399-414.

32
''Levine, R. R. 1973. Pharmacology. Drug Actions and Reactions. Little,
Brown and Co., Boston. p. 333.

McNair, D. M. and M. Lorr. 1964. An analysis of mood in neurotics. J.
Abnorm. Soc. Psychol. 69:620-627.

Montagu, J. D. 1972. Effects of diazepam on the EEG in man. Eur. J.
Pharmac. 17:167-170.

Moskowitz, H. 1974. Drug effects in relation to industrial safety.
pp- 333-347. In: C. Xintaras,.B. L. Johnson, and I. de Groot, Ed.
Behavioral Toxicology. U. S. Dept. of HEW, NIOSH.

Moskowitz, H., and S. Sharma. 1974. Effects of alcohol on peripheral vision
as a function of attention. Human Factors. 16:174-180.

Pook, G. K. 1967. Prediction of Elemental Motion Performance Using
Personnel Selection Tests. Ph.D. Thesis. University Microfilms, Inc.
Ann Arbor, Michigan

Robinson, S. 1974. Physiology of muscular exercise, In: V. B. Mountcastle,
Ed. Medical Physiology. The C. V. Mosby Co., St. Louis, Missouri.
2:1273-1304, 13th ed.

Roche Laboratories. Valium® (Diazepam) tablets, package insert issued
January, 1975. Div. of Hoffman-LaRoche Inc., Nutley, N.J.

Sellman, R., J. Kanto, E. Raijola, and A. Pekkarinen. 1975. Induction effect
of diazepam on its own metabolism. Acta. Pharmacol. Toxicol. 37:345-351.

Sidell, F. R., and J. E. Pless. 1971. Ethyl alcohol: blood levels and
performance decrement after oral administration to man. Psychopharmacologia
(Berl.). 19:246-261.

Stewart, R. D., C. L. Hake, H. V. Forster, A. J. Lebrun, J. E. Peterson,
A. Wu, and Staff. 1974. Tetrachloroethylene: development of a biologic
standard for the industrial worker by breath analysis. Report No. NIOSH-
MCOW-ENVM-PCE-74-6. NIOSH. Cincinnati, Ohio

Stewart, R. D., C. L. Hake, and A. Wu. 1976. Use of breath analysis
to monitor methylene chloride exposure. Scand. J. Work, Environment,
Health. 2:57-70.

36
''WEEK

10

11

12

TABLE I
PERC/DRUG STUDY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1975
MONDAY TUESDAY WEDNESDAY THURSDAY FRIDAY SATURDAY
29 [30] Ly T2l orrenrarion [Lal al
TRAINING TRAINING
| 6! tii. O ppm * 8) 0 ppm | 9 25 ppm [10] 100 ppm [ial v-6
TRAINING 2. no drug no orug no drug no drug ms
= 3. Gp A Cp B Gp A Gp B
[13h ppm 14 Jo ppm 115]100 ppm [1695 ppm L17l100 ppm | 18)
V- 6 mg V- 6 mg V- 6 mg 'V- 6 mg V- 6 mg Placebo
Gp B Gp B Gp _ B Gp B Gp B
12019 ppm 21 ]o ppm 22]100 ppm 23]95 ppm L24h00 ppm 25]
Placebo Placebo Placebo Placebo Placebo
Gp A Gp B Gp A _| Gp Bot Gp Be
[2710 ppm 28)0 ppm 29|100 ppm 130|25 ppm [31]100 ppm al
Alc.-0.75ml/kg Alc.-0.75ml1/kg Alc.-0.75m1/kg Alc.-0.75m1/kg Alc.-0.75ml/kg
Gp A Gp A Gp A Gp A Gp A
| 3;100 ppm | 4 Jo ppm | Slo ppm 6125 ppm | zhoo ppm | 8i
no drug no drug no drug no drug no drug Placebo
Gp A Gp B Gp A Gp B Gp B __ 4
10/0 ppm 110 ppm 12|100 ppm 13|25 ppm 141100 ppm 15]
[Placebo Sake seeds lacebo . Placebo V-12 mg
Gp A Gp B Gp A Gp B Gp B
[17}0 ppm 1180 ppm 19|100 ppm 20)25 ppm 121100 ppm 221
V-12 ng V-12 mg V-12 mg V-12 mg V-12 mg
Gp B Gp B Gp B _ GpB ___Gp_B
[241 25 26 | 27] 2 2a]
No STUDIES THIS WEEK THANKSGIVING HOLIDAYS
| Uy ppm | 2, ppm L300 ppm abs ppm hoo ppm wi
Alc.-1.50m1/kg Alc.-1.50 ml/kg | Alc.-1.50m1/kg Alc.-1.50m1/kg Alc.-1.50m1/kg
Gp Gp A Gp A Gp A Gp_A
| 8/100 ppm | 9 jo ppm 100 ppm vay bs ppm 12/00 ppm 13
no drug no drug no drug no drug no drug
Gp A Gp B Gp A Gp B Gp B 4
no drug Ba: GEG ne Srug PHYSICAL EXAMINATIONS
Gp A Gp_A Gp B 7
* 1. Concentration of PCE in chamber.

2. V = VALIUM
3. Gp of 6 subjects who will have EEG's.

in daily dose, or alc. = ml of 100 proof vodka per kg body weight.
Other group of. 6 subjects will carry out eye function tests.

PmMmwBonoand

AmMwemao2w

Amo ZmMamv
''8E

WEEK

10

a1

i2

TABLE II
PERC/DRUG STUDY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1975
|
MONDAY TUESDAY WEDNESDAY THURSDAY | FRIDAY SATURDAY
29 30 1 Al 3] 4
29 | 30] ORIENTATION ~H
TRAINING TRAINING _
6] 7h1. 0 ppm * 8] 0 ppm |_| 25 ppm 10] 100 ppm [11]
2. no drug no drug no drug no drug V - 6 mg i
TRAINING a Ge ok Gp B Gp A Gp B '
[13] 0 ppm 14 |p ppm 15! 100 ppm [16] 25 ppm [17 | 100 ppm | 18] |
WV 6 2 V- 6 mg V- 6 mg V- 6 mg V- 6 mg Placebo
Gp B Gp B Gp_B Gp B Gp B
O ppm 121 |p ppm |22| 100 ppm [23 | 25 ppm [24] 100 ppm [25]
Placebo Placebo Placebo Placebo Placebo j
Gp A Gp B Gp_A Gp Bo eo oe .
127] 0 ppm 28 by ppm 29] 109 30] 95 ppm 31 Bi
Alc.-b.75m1/kg | alc.?b"75m1/kg Ale. -0. Paks Mig =D rewifke || Micet, Bal /ke
Gp A Gp A Gp_A Cp
| 3] 100 appa | 4b ppm To O ppm | 6| 25 ppm 7] 100 ppm |_ 8]
drug no drug no drug no drug no drug V - 10 mg
Gp A Gp B Gp A Gp B Gp B
110] 0 ppm 11) ppm 12] 100 ppm 113 | 25 ppm 14] 100 ppm 115]
V-10 mg V-10 mg V-10 mg V-10 mg V-10 mg Placebo
Gp B Gp B Gp B Gp B Gp B
17} 0 ppm 118 b ppm 19 | 100 ppm 20 | 25 ppm 121 | 100 ppm 122 |
Placebo Placebo Placebo Placebo Placebo
Gp A Gp B Gp A Gp_B rT B —4
[24 | 25 ppm 25 b ppm 26 26 | O ppm * 128 29
fo drug no dene ‘no drug THANKSGIVING HOLIDAYS
Gp_A CoA ls oT <== rel :
1 4 5
a soma /kg fail PE 0 Sang EE a5
aie.” -50ml/kg | Alc.-1.50 ml/kg | Alc. if ml/kg -_ cole O ml/kg {Alc. li ml/kg V - 6 mg
Gp A Gp A Gp_A Gp '
810 ppm 9b ppm 0 | 100 ppm lo ppm Tio ppm 3
V- 6 mg V- 6 mg V- 6 mg = 6 mg V- 6 mg
Gp_B Gp B Cp B B p_B. 5
1151 100 ppm D5 ppl 27 10 ppm TBI 95 ppm 19100 ppm 20}
no drug no drug no drug . no drug no drug : Phys. Exams
Gp A Gp B Gp_A t Gp B a Gp_B A
* 1. Concentration of PCE in chamber. .
2. V = VALIUM in daily dose, or Alc. = approx. ml of 100 proof vodka per kg body weight (dose adjusted

3. Gp of 6 subjects who will have EEG's.

Other

individually).

group of 6 subjects will carry out visual function tests.

AMwmonaod

PMB RmMdIoO-m

AMwdrmMoanms
''TABLE III

SUBJECTS PARTICIPATING IN STUDY

SUBJECT ASSIGNED HEIGHT WEIGHT
NUMBER GROUP AGE _(em.) _(kg.)
FEMALE
95 A 37 164 62.3
326 A 25 170 61.1
327 A 19 165 59.2
328 B 25 162 81.6
329 B 27 172 56.6
330 B 24 160 61.0
MALE
117 A 27 171 75.8
123 A 42 173 69.2
331 A 33 182 78.4
332 B 22 170 59.8
333 B 23 180 59.8
334 B 29 178 84.8

39
''TABLE IV

SUMMARY OF SUBJECT ATTENDANCE DURING STUDY

SUBJECT POTENTIAL TOTAL DAYS TOTAL DAYS
NUMBER & SEX DAYS, TOTAL PRESENT ABSENT
GROUP A
95, F 55 54 1
326, F 19° 19 0
327, F 55 45 10
117, M 55 48 7
123, M 32b 22 10
331, M 17-172" 17-143 0
GROUP B
328, F 55 47 8
329, F 55 54 1
330, F 55 55 0
332, M 55 50 5
333, M 53° 51 2
334, M 55 53 2

 

4 withdrew from study

b withdrawn from study

alternate subject

40
''TABLE V

PCE CONCENTRATION IN EXPOSURE CHAMBER

TWA and SD in ppm

 

 

 

41

 

 

ADDIT. | .
WEEK | EXPOSURE Monday Tuesday | Wednesday | Thursday | Friday Saturday | Sunday
<a sep yasemEanas ! ; L
! / 10 20 3 25.1 4100.1 5 6
2 none | +0.9 a an
-— \ i f. ‘ | |
|
3. Valium | 7 0 8 «0 9 99.9 / 1025.7 1199.8 | 12 | 13
| 6 mg ! +3.4 : *1is0 ts ae ;
4 | Placebo |! ]4 0 15 0 [6101.5 | 1725.2 18 100.0; 19 20
| +4.9 +0.9 +2. 9 | .
5 | Alcohol | 2] 0 yn 93 100.1 9425.0 | 95 100.7 6 | 7
0.75m1/kg, | | +2.9 +0.6 | +4.1 5 |
ants .
6 none ' 28100.3 ,; 29 0 | 300 3] 25.2 | 3299.9 53 34
. , ea Le #14 | ion |
7° Valium ‘| 35 0 | 36 0 | 37, 101.0 3325.4 39100.2 YQ 4]
10 mg | +3.5 41.3 0 +3.7
8 Placebo | 42 0 43 0 yhog.8 | 4525.1 4699.2. 47 et)
ee | +33 | +1.0 | +2. a i
|
9 none / 49 25.3 | 50 0 | 510 52 53 Sy 55
| ot RO THANKSGIVING HOLIDAYS
10 Alcohol | 56 0 57 0 58100.3 , 5925.7 6099.7. 61 62
1.5m1/kg | 5 $4.00 | +1.2 +3.6
pei | “ i. a
11 Valium | 63 0 64 0 65 100.8 | 6625.0 6799.8 68 69
6 mg | . 43.2 41.000 #302 ;
|
12 none | 70 100.0 7] 0 720 | 7325.4 74 100.3
43.5 +1.1 +3.1
''TABLE VI

ML VODKA CONSUMED BY SUBJECTS DAILY DURING WEEKS 5 & 10

GROUP A
SUBJECT SEX WEEK 5 WEEK 10
95 F 64 ml 90 ml
326 F out of study out of study
327 F 55 ml 90 ml
117 M 76 ml 110 ml
123 M 65 ml out of study
331 M 75 ml out of study
= GROUP B
SUBJECT SEX WEEK 5 WEEK 10
328 F 60 ml 120 ml
329 F 56 ml 90 ml
330 F 60 ml 90 ml
332 M 62 ml 100 ml
333 M 60 ml 100 ml
334 M 75 ml 100 ml

42
''TABLE VII

DEVIATIONS TO DIAZEPAM AND PLACEBO DOSES

WEEK 3: Three diazepam capsules/day, with meals, starting on weekend.

WEEKEND

MONDAY =

TUESDAY

WEDNESDAY

THURSDAY

FRIDAY

328 missed 1 dose; 331 missed 3 doses; 332 missed 1 dose; 334 missed
7 doses (all).

331 missed breakfast dose; 334 missed breakfast dose.
327 missed breakfast dose.

117 missed breakfast dose.

327 missed supper dose; 331 missed supper dose.

327 missed breakfast dose.

WEEK 4: Three placebo capsules/day, with meals, starting on weekend.

WEEKEND

MONDAY

TUESDAY

WEDNESDAY

THURSDAY

FRIDAY

326, 328, 331 and 333 missed 1 dose.

117 and 123 absent.

123 absent; 331 missed breakfast dose.

123 & 327 absent; 329:- no doses after breakfast.
123 absent; 329 - no doses.

123 absent.

WEEK 7: Two diazepam capsules/day, w/breakfast and supper, starting on weekend.

WEEKEND

MONDAY

TUESDAY

WEDNESDAY

THURSDAY

FRIDAY

327 missed 5 doses (all).

123 absent.

123 absent.

123 and 332 absent, no doses.
123 absent.

123 absent; 300 missed chamber dose due to nausea.

43
''TABLE VII (continued)

WEEK 8: Two placebo capsules/day, w/breakfast and supper, starting on weekend.

WEEKEND - No recorded deviations.

MONDAY - 117 and 327 absent, missed 2 doses.
TUESDAY - 327 absent, missed 2 doses.
WEDNESDAY - No recorded deviations.

THURSDAY - No recorded deviations.

FRIDAY - 328 absent.

WEEK 11: Three diazepam capsules/day, with meals, starting on weekend.

WEEKEND - 327 missed 3 doses; 333 missed 1 dose.
MONDAY - 328 absent, missed 1 dose.

TUESDAY - 328 missed 3 doses; 333 absent, no doses.
WEDNESDAY - 327 and 328 absent; 328 no doses.
THURSDAY - 328 absent.

FRIDAY - 117, 328, and 332 absent.

44
''DAY
DAY
DAY
DAY

DAY

DAY
Day
Day
Day

Day

TIME OF SAMPLE

TABLE VIII

PCE BLOOD CONCENTRATIONS

WEEK: 2 (Control)

 

 

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of* Exposure

Baseline
2' of Exposure

PCE CHAMBER PCE BLOOD CONC., PPM NO. OF
CONC. , PPM MEAN RANGE +$.D. SUBJECTS
MALES
no exposure
0
0
25
0.7 0.6-1.0 0.2 6
100
13.9 7.9-21.0 5.0 5
FEMALES
no exposure
0
0
25
0.6 0.3-0.8 0.2 6
100
7e2 4.0-10.1 203 6

45
''DAY

DAY

DAY

DAY

DAY

DAY

Day

Day

Day

Day

TABLE IX

PCE BLOOD CONCENTRATIONS

WEEK: 3 (Valium, 6 mg.)

 

 

PCE CHAMBER PCE BLOOD CONC., PPM NO. OF
TIME OF SAMPLE CONC., PPM MEAN RANGE +S.D. SUBJECTS
MALES
Baseline 0 Q.1 0.0-0.4 0.2 6
2' of Exposure
Baseline 0
2' of Exposure 0.1 0.0-0.4 0.2 6
Baseline 100
2' of Exposure 8.8 7.0-9.6 1.0 6
Baseline 25 0.3 0.2-0.7 0.2 6
2' of Exposure 1.0 0.8-1.2 0.4 6
Baseline 100 O.1 0.0-0.2 0.1 6
2' of Exposure 9.7 5.7-12.2 2.6 5
FEMALES

Baseline 0 0.1 0.0-0.2 Oved 6
2' of Exposure
Baseline 0 0.2 0.0-0.4 0.1 5
2' of Exposure
Baseline 100
2' of Exposure 9.0 6.7-11.3 1.8 6
Baseline 25 0.4 0.3-0.8 0.1 6
2" of Exposure 0.8 0.6-1.0 0.1 6
Baseline 100

8.2 6.3-10.4 1.5 6

2' of Exposure

46
''DAY

DAY

DAY

DAY

DAY

DAY

Day

Day

Day

Day

TIME OF SAMPLE

TABLE X
PCE BLOOD CONCENTRATIONS

WEEK: 4 (Placebo)

PCE BLOOD CONC., PPM

 

 

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

PCE CHAMBER NO. OF
CONC., PPM © MEAN RANGE mur SUBJECTS
MALES

0 2 0.1-0.3 0.1 3

0

100
9.1 7.8-10.8 1.2. 5

25
1.8 1.4-2.2 0.3 5

100
Toh 7.0-8.6 0.7 5

FEMALES

0
0.4 0.3-0.6 0.1 6
0 0.1 0.0-0.8 0.3 6
100 <0.1 0.0-0.2 0.1 6
8.5 7.1-9.2 1.0 4
25 <O.1 0.0-0.2 0.1 5
1.4 1.0-1.8 0.3 5

100
6.9 5.9-8.8 13 5

47
''TABLE XI
PCE BLOOD CONCENTRATIONS

WEEK: 5 (Alcohol, 0.75 ml/kg)

 

 

PCE CHAMBER PCE BLOOD CONC., PPM NO. OF
TIME OF SAMPLE CONC., PPM MEAN RANGE +S.D. SUBJECTS
MALES
DAY 1: Baseline 0
2' of Exposure
DAY 2: Baseline 0
2' of Exposure
DAY 3: Baseline 100
2' of Exposure 7.0 5.6-8.4 1.3 5
DAY 4: Baseline 25 O« 1 0.0-0.3 0.1 5
2' of Exposure 265 1.8-3.2 0.6 5
DAY 5: Baseline 100
2' of Exposure 8.7 6.4-12.0 203 5
FEMALES
DAY 1: Baseline 0
2' of Exposure
Day 2: Bascline 0
2' of Exposure
Day 3: Baseline 100
2' of Exposure 8.5 7.6-9.2 0.8 4
Day 4: Baseline 25 0.1 0.0-0.2 0.1 4
2" of Exposure 2.7 2.1-3.2 0.6 4
Day 5: Baseline 100 0.1 0.0-0.2 0.1 6
2' of Exposure 9 «6 8.0-12.0 1.8 5

48
''TABLE XII
PCE BLOOD CONCENTRATIONS

WEEK: 6 (Control)

 

 

PCE CHAMBER PCE BLOOD CONC., PPM NO. OF
TIME OF SAMPLE CONC., PPM MEAN RANGE +5 .D. SUBJECTS
MALES
DAY 1: Baseline 100
2' of Exposure 7.3 6.2-9.0 1.1 5
DAY 2: Baseline 0
2' of Exposure
DAY 3: Baseline 0
2' of Exposure
DAY 4: Baseline 29
2' of Exposure 1.6 1.4-2.0 0.3 4
DAY 5: Baseline 100 0.5 0.4-0.7 0.1 4
2' of Exposure 7.3 6.6-8.8 0.8 5
FEMALES
DAY 1: Baseline 100 0.4 0.4-0.5 <0.1 4
2' of Exposure 7.8 5.8-9.0 1.3 5
Day 2: Baseline 0 0.4 0.0-0.7 0.4 5
2' of Exposure
Day 3: Baseline 0
2' of Exposure
Day 4: Baseline 25
2' of Exposure 1D 1.3-1.7 0.2 4
Day 5: Baseline 100 0.6 0.3-0.9 0.2 4
2' of Exposure 7.2 5.8-8.4 Lawl. 4

49
''TABLE XIII

PCE BLOOD CONCENTRATIONS

WEEK: 7 (Valium, 10 mg)

 

PCE CHAMBER PCE BLOOD CONC., PPM NO. OF
TIME OF SAMPLE CONC., PPM MEAN RANGE £S..D.. SUBJECTS
MALES
DAY 1: Baseline 0 0.3 0.0-0.4 0 aid 3
2' of Exposure
DAY 2: Baseline 0
2' of Exposure
DAY 3: Baseline 100
2' of Exposure 10.5 7.6-13.2 2.8 3
DAY 4: Baseline 25
2' of Exposure 2..2 1.5-2.6 0.5 4
DAY 5: Baseline 100 0.6 0.4-0.8 0.2 4
2" of Exposure 12.7 10.8-14.7 Led 4
FEMALES
DAY 1: Baseline 0 0.5 0.0-0.6 0.3 5
2' of Exposure
Day 2: Baseline 0
2' of Exposure
Day 3: Baseline 100
2' of Exposure 9.4 7.5-11.1 1.5 5
Day 4: Baseline 25 0.4 0.0-0.8 0.3 5
2' of Exposure Bied 2.7-4.2 0.6 5
Day 5: Baseline 100 0.5 0.3-0.8 0.2 5
2' of Exposure 10.8 8.2-13.8 205 4

50
''DAY

DAY

DAY

DAY

DAY

DAY

Day

Day

Day

Day

PCE BLOOD CONCENTRATIONS

 

WEEK:
PCE CHAMBER

TIME OF SAMPLE CONC., PPM
Baseline 0

2' of Exposure

Baseline 0

2' of Exposure

Baseline 100

2' of Exposure

Baseline 25

2' of Exposure

Baseline 100

2' of Exposure

Baseline 0

2' of Exposure

Baseline 0

2' of Exposure

Baseline 100

2' of Exposure

Baseline 25

2' of Exposure

Baseline 100

2' of Exposure

TABLE XIV

 

8 (Placebo)
‘PCE BLOOD CONC., PPM NO. OF
MEAN RANGE +$.D. SUBJECTS
MALES
1.1 1.0-1.2 0.1 3
0.2 0.0-0.5 0.2 4
< Ow. 0.0-0.2 0.1 4
5.9 4.6-7.3 1.1 4
0.4 0.4-0.5 Osl 3
le3 1.2-1.5 0.1 4
0.6 0.5-0.8 0.1 4
7.9 6.5-9.5 1.4 4
FEMALES

1.2 1.2-1.4 0.1 4
0.3 0.2-0.6 0.2 4
0.1 0.0-0.4 0.2 5
7.2 5.0-8.6 195 D
0.4 0.3-0.6 0.1 5
1.2 0.9-1.5 0.3 4
0.5 0.4-0.5 <0O.1 3
7.4 6.5-8.4 0.9 4

SL
''DAY

DAY

DAY

DAY

DAY

DAY

Day

Day

Day

Day

TIME OF SAMPLE

TABLE XV

PCE BLOOD CONCENTRATIONS

 

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2" of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

 

WEEK: 9 (Control)
PCE CHAMBER PCE BLOOD CONC., PPM NO. OF
CONC., PPM MEAN RANGE £S «DD. SUBJECTS
MALES
25 0.4 0.3-0.5 Oud 3
1.7 1.6-1.8 0.2 3
0 07 0.7-0.9 0.1 3
0 0.1 0.1-0.2 <0.1 2
no exposure
no exposure
FEMALES
25 0.4 0.0-0.8 0.3 5
Ls? 1.6-1.8 0.1 5
0 0.6 0.4-0.8 0.1 5

no exposure

no exposure

52
''TABLE XVI
PCE BLOOD CONCENTRATIONS

WEEK: 10 (Alcohol, 1.5 ml/kg)

 

 

PCE CHAMBER PCE BLOOD CONC., PPM NO. OF
TIME OF SAMPLE CONC., PPM MEAN RANGE +S$.D. SUBJECTS
MALES
DAY 1: Baseline 0
2' of Exposure
DAY 2: Baseline 0
2' of Exposure
DAY 3: Baseline 100 ‘
2' of Exposure 7.4 7.0-8.4 0.7 4
»
DAY 4: Baseline 25 0.7 0.5-0.8 0.2 4
2' of Exposure 3.0 2.8-3.2 0.2 4
DAY 5: Baseline 100 0.3 0.2-0.6 0.2 3
2' of Exposure 6.8 6.0-8.1 1.1 3
FEMALES
DAY 1: Baseline 0
2' of Exposure
Day 2: Baseline 0
2' of Exposure
Day 3: Baseline 100
2' of Exposure 7.3 6.0-8.5 1.2 4
Day 4: Baseline 25 0.7 0.6-0.7 <O.1 4
2' of Exposure 3.0 2.7-3.5 0.3 5
Day 5: Baseli 100 0.4 0.4-0.5 0.1 4
“ Se Ee 7.0 6.0-8.3 1.1 4

2' of Exposure

53
''TABLE XVII

PCE BLOOD CONCENTRATIONS

WEEK: 11 (Valium, 6 mg)

 

 

PCE CHAMBER PCE BLOOD CONC., PPM NO. OF
TIME OF SAMPLE CONC., PPM MEAN RANGE +$.D. SUBJECTS
MALES
DAY 1: Baseline 0 0.3 0.3-0.4 <0.1 3
2' of Exposure
DAY 2: Baseline 0
2' of Exposure
DAY 3: Baseline 100
2' of Exposure 33 2.5-4.2 0.7 4
DAY 4: Baseline * 25
2' of Exposure 1.4 1.1-1.6 0.2 4
DAY 5: Baseline 100
2" of Exposure 8.6 8.0-9.2 0.8 2
FEMALES
DAY 1: Baseline 0 0.4 0.3-0.4 <O.1 4
2' of Exposure
Day 2: Baseline 0
2' of Exposure
Day 3: Baseline 100
2' of Exposure 3.8 3.0-4.9 1.0 3
Day 4: Baseline 25
2' of Exposure 2.0 1.8-2.1 0.1 4
Day 5: Baseline 100
2' of Exposure 8.2 7.5-8.8 0.5 4

54
''DAY 1:

DAY

DAY

DAY

DAY

DAY

Day

Day

Day

Day

TIME OF SAMPLE

TABLE XVIII
PCE BLOOD CONCENTRATIONS

WEEK: 12 (Control)

 

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

Baseline
2' of Exposure

 

PCE CHAMBER PCE BLOOD CONC., PPM NO. OF
CONC., PPM MEAN RANGE £S Ds. SUBJECTS
MALES
100
10.9 9.9-11.7 0.9 3
0
0
25 2.2 1.6-2.7 0.5 4
100
9.8 8.7-11.2 de 1 4
FEMALES
100
0
0
22
100

55
''TABLE XIX
PCE BREATH CONCENTRATIONS
WEEK: 2 (Control)

PCE CHAMBER PCE BREATH CONC., PPM
CONC., PPM MEAN RANGE +S.D.

NO. OF

TIME OF SAMPLE SUBJECTS

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline,

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2" of Exposure
15"" Post Exposure
30" Post Exposure

Baseline

2" of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

MALES

no exposure

25

whan
art

100

rdw
nHnOoor
Nnunon

FEMALES

no exposure

25

100

56

PHU
Rou
se ttrido
Hob

wowhrre

ooo
wow

NNNO
NWR N

anand

monn

aaa

ANaNaAU
''TABLE XX

PCE BREATH CONCENTRATIONS

WEEK: 3 (Valium, 6 mg)

 

PCE CHAMBER PCE BREATH CONC., PPM NO. OF
TIME OF SAMPLE CONC. , PPM MEAN RANGE £5.D. SUBJECTS
MALES
DAY 1: Baseline 0 1.3 0.8-1.9 0.5 5
2' of Exposure
15" Post Exposure
30" Post Exposure
DAY 2: Baseline 0 0.9 0.6-1.1 0.2 6

2' of Exposure
15" Post Exposure 0.7 0.5-1.0 0.2 6
30" Post Exposure

DAY 3: Baseline, 100 0.6 0.67-0.6 0 6
2' of Exposure 33.8 29.2-36.7 3.0 6
15" Post Exposure 20.5 15.8-22.3 2.4 6
30" Post Exposure 16.8 13.6-20.9 2.6 6

DAY 4: Baseline 25 3.4 2.9-3.8 0.4 6
2' of Exposure 12.8 10.5=15 .3 1.6 6
15" Post Exposure 8.8 7.6-10.5 1.1 6
30" Post Exposure 75 6.7-8.38 0.8 6

DAY 5: Baseline 100 1.3 1.1-1.6 0.3 6
2' of Exposure 47.0 31.0-59.9 9.9 6
15"" Post Exposure 29.0 25.4-33.8 2.8 6
30" Post Exposure 23.9 18.3-26.8 3:2 6

FEMALES

DAY 1: Baseline 0 1.9 1.3-2.9 0.6 6
2' of Exposure
15" Post Exposure
30" Post Exposure

DAY 2: Baseline 0 0.8 0.5-1.1 0.2 6
2' of Exposure
15" Post Exposure 1.0 0.8-1.1 Ocl 5
30" Post Exposure

DAY 3: Baseline 100 0.6 0.5-0.9 0.1 6
2' of Exposure 31.7 21.0-38.1 5.9 6
15" Post Exposure 19.4 15.1-25.2 3.9 6
30" Post Exposure 15.2 9.4-19.4 3.5 6

DAY 4: Baseline 25 Sid 2.3-4.1 0.6 6
2' of Exposure 12.0 9.1-14.1 1.8 6
15" Post Exposure 8.1 6.8-9.4 1.0 5
30" Post Exposure 6.4 4.1-7.3 1.1 6

DAY 5: Baseline 100 1.0 0.9-1.0 0.1 6
2' of Exposure 51.4 43.7-57.7 6.6 6
15" Post Exposure 29.6 19.7-40.8 7.0 6
30" Post Exposure 22.3 17.7-27.5 3.4 6

57
''TABLE XXI
PCE BREATH CONCENTRATIONS

WEEK: 4 (Placebo)

 

PCE CHAMBER PCE BREATH CONC., PPM NO. OF
TIME OF SAMPLE CONC. , PPM MEAN RANGE +S.D. SUBJECTS
MALES

DAY 1: Baseline 0 1.2 1.1-1.5 0.2 4
2' of Exposure
15" Post Exposure 0.9 Ov7E1.2 O02 4
30" Post Exposure

DAY 2: Baseline 0 1.0 1.0-1.1 0 5
2' of Exposure
15" Post Exposure 0.9 0.7-1.1 0.2 3
30" Post Exposure

DAY 3: Baseline 100 0.9 0.5-1.0 Ow2: 5
2" of Exposure 34.6 29.2-39.6 348 5
15" Post Exposure 2151 16.7-23.4 208 5
30" Post Exposure 18.0 14.1-19.8 205 5

DAY 4: Baseline 25 3.3 2.2-4.4 0.8 5
2' of Exposure 12.7 12.1-14.3 0.9 5
15" Post Exposure 6.1 4.7-7.7 Led 5
30" Post Exposure 6.1 5.2-7.2 0.8 5

DAY 5: Baseline 100 2.7 2.3-3.7 0.6 5
2' of Exposure 38.9 33.2-44.2 4.2 5
15" Post Exposure 22.0 19.4-26.7 2.9 5
30" Post Exposure 19.5 14.7-22.1 Ie 5

FEMALES

DAY 1: Baseline 0 1.4 1.2-1.8 0.2 6
2' of Exposure
15" Post Exposure 1.3 1.2-1.8 0.3 5
30" Post Exposure

DAY 2: Baseline 0 1.0 0.8-1.1 0.2 6
2' of Exposure
15" Post Exposure 0.9 0.7-1.1 0.2 3
30" Post Exposure

DAY 3: Baseline 100 0.9 0.8-1.0 0.1 6
2' of Exposure 35.9 28.1-41.6 6.8 4
15" Post Exposure 21.08 19.2-27.1 4.6 3
30" Post Exposure 18.7 15.6-23.4 4.1 3

DAY 4: Baseline 25 Za 2.2-3.9 0.7 5
2' of Exposure 11.4 9.9-12.1 0.9 5
15" Post Exposure Gal. 4.9-8.2 1.3 5
30" Post Exposure Sul, 3.8-6.0 0.9 4

DAY 5: Baseline 100 2.4 1.8-2.8 0.5 5
2" of Exposure 36.9 27.6-46.1 6.6 6
15" Post Exposure 20.8 17.1-28.1 4.4 6
30" Post Exposure 19\,2 14.7-25.8 4.4 6

58
''DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

TIME OF SAMPLE

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline,

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30"" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

TABLE XXII

PCE BREATH CONCENTRATIONS

WEEK: 5 (Alcohol, 0.75 ml/kg)

 

PCE CHAMBER PCE BREATH CONC., PPM NO. OF
CONC. , PPM MEAN RANGE +8 .D SUBJECTS
MALES
0 1.8 0 -2.6 1.1 5
0
100
325.3 23.1-36.5 5.6 2
16.5 10.6-22.1 4.2 5
14.7 10.1-20.2 4.3 5
25 3.8 3.0-4.5 0.6 4
15.2 14.9-16.4 0.7 5
9.5 765-11,.2 1.3 5
8.3 6.3-9.7 1.5 5
100 2.7 2.5-301 0.3 5
36.3 32.5-42.5 3.8 5
16.5 13.1-20.0 267 5
12.5 11.3-13.8 Lol 4
FEMALES
0 1.9 1.2-2.3 0.4 6
0
100
31.3 25.0-38.5 5.5 4
16.9 14.4-20.2 2.7 >
15.4 11.5-18.8 3.0 4
25 3.9 3.0-4.5 0.7 4
13.4 10.4-14.9 2.1 4
9.8 8.2-11.9 1.6 4
8.2 6.0-9.7 1.6 4
100 2.3 1.8-2.5 O53 5
34.5 25.0-40.0 5.7 5
16.5 13.8-18.8 2.6 5
13.1 11.3-16.3 2.3 5

59
''DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

TIME OF SAMPLE

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2" of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

TABLE XXIII

PCE BREATH CONCENTRATIONS

WEEK: 6 (Control)

 

 

PCE CHAMBER PCE BREATH CONC., PPM NO. OF
CONC. , PPM MEAN RANGE +S8..D; SUBJECTS
MALES
100 3.1 2.5-4.5 1.0 4
33.1 28.2-39.5 4.4 5
18.8 13.6-22.1 3.3 5
16.1 11.8-20.5 5.3 5
0 4.1 3.8-4.5 0.3 5
)
25 1.4 1.1-1.8 0.3 5
11.6 10.8-12.9 0.9 4
7.9 7.5-8.1 0:3 4
si 6.9-7.3 0.2 4
100 2.6 1.3-3.4 0.9 5
30.5 28.1-34.9 2.6 5
18.5 16.2-20.8 1.8 5
16.4 14.1-17.7 1.5 5
FEMALES
100 3.2 2.8-3.4 0.3 5
35.6 97. 1-39:.0 4.9 5
19.8 18.4-22.1 1.4 5
17.2 15.4-19.0 1.4 5
0 3.5 3.0-3.8 0.3 5
0
25 1.4 1.1-1.8 0.3 4
023 10.5-12.5 0.9 4
8.5 8.1-8.6 0.3 4
7.5 7.3-7.8 0.2 4
100 2.4 1.9-3.4 0.6 5
26.3 19.3-34.9 6.6 4
18.0 13.6-23.2 4.1 4
17.0 13.6-20.8 3.0 4

60
''DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

TIME OF SAMPLE

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline,

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

TABLE XXIV

PCE BREATH CONCENTRATIONS

 

 

WEEK: 7 (Valium, 10 mg)
PCE CHAMBER PCE BREATH CONC., PPM NO. OF
CONC., PPM MEAN RANGE #8.D. SUBJECTS
MALES
0 202 2.1=2.3 0.1 3
0 1.1 0.9-1.5 0.2 4
100 1.5 1.4-1.7 0.2 3
27.5 24.0-31.1 3.6 3
18.7 15.0-21.2 3.3 3
16.4 13.7-18.5 265 3
25 3.0 1.8-4.1 0.9 4
11.1 9.9-12.3 1.4 4
8.2 6.7-8.8 1.0 4
Th 5.3-9.2 1.6 4
100 3.0 2.7-3.4 0.3 4
33.1 31.3-34.2 1.4 4
18.0 16.6-20.2 1.7 4
16.2 13.6-19.0 2.6 4
FEMALES
0 2.1 1.4-2.5 0.5 5
0 1.2 0.9-1.5 0,2 5
100 1.5 0.7-2.0 0.6 5
28.4 23.3-31.1 3.2 5
16.6 14.6-19.2 2.1 5
14.64 13.0-16.4 LZ 5
25 3.2 2.8-3.7 0.3 5
11.9 10.2-13.0 lil 5
8.1 6.5-9.5 Lsl 5
7.1 6.0-8.1 1.0 5
100 335 3.1-4.3 0.5 5
31.9 29.9-35.7 2.6 4
15.5 14.0-16.3 1s 4
14.2 12.0-17.1 2.3 4

61
''DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

TIME OF SAMPLE

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline,

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

TABLE XXV

PCE BREATH CONCENTRATIONS

WEEK: 8 (Placebo)

 

62

PCE CHAMBER PCE BREATH CONC., PPM NO OF
CONC. , PPM MEAN RANGE +8.D. SUBJECTS
MALES
0 342 3.0-3.5 0.2 3
0 2.3 2.1-2.6 0.3 4
100 1.9 1.6-2.3 0.3 4
30.3 27,.5-32.1 1.9 4
19.4 18.3-21.9 1.7 4
1643 15.0-18.3 1.6 4
25 3.0 2.8-3.2 0.2 4
10.0 9.1-11.2 0.9 4
7.3 6.7-8.0 0.5 4
629 6.6-7.1 0.2 4
100 3.0 2, 9-3.1 0.1 4
27.6 25.8-30.9 2.4 4
16.7 12.0-21.1 4.0 4
14.7 11.4-17.5 2.8 4
FEMALES
0 3.9 3.5-4.3 0.4 4
0 2.5 1.5-3.0 0.7 4
100 1.7? 1.3-2.6 0.6 5
29.72 25..6-32.7 2.8 5
16.2 13.4-19.0 2.7 5
15.5 13.8-17.7 2.0 3
25 3.0 2.7=3.2 0.2 5
11.3 10.7=-12.6 0.8 >
7.9 7.5-9.4 0.8 5
6.6 6.2-7.0 0.3 5
100 3.0 2.6-3.3 0.3 4
26.9 23..7-32.0 3.7 4
16.2 14.0-18.6 1.9 4
14.5 11.4-16.5 233 4
''TABLE XXVI

PCE BREATH CONCENTRATIONS

WEEK: 9 (Control)

PCE CHAMBER PCE BREATH CONC., PPM NO. OF
TIME OF SAMPLE CONC., PPM MEAN RANGE +8.D. SUBJECTS

 

S

DAY 1: Baseline 25 2.5
2' of Exposure 8.8

15" Post Exposure 6.9

30" Post Exposure D6

HONH
EAWO
Wwww

DAY 2: Baseline 0 203 2.0-2.5 0.3 3
2' of Exposure
15"" Post Exposure
30" Post Exposure

DAY 3: Baseline 0 1.4 1.3-1.5 0.1 2
2' of Exposure
15" Post Exposure
30" Post Exposure

DAY 4: Baseline no exposure
2' of Exposure
15" Post Exposure
30" Post Exposure
DAY 5 Baseline no exposure
2' of Exposure
15" Post Exposure
30" Post Exposure

DAY 1: Baseline 25 254
2' of Exposure 1.0
15" Post Exposure 7.0
30" Post Exposure 5.9

ooro
WOWW
mMnan

DAY 2: Baseline 0 25:2 1.9-2.7 0.3 5
2' of Ex, 2sure
15" Post Exposure
30" Post Exposure

DAY 3: Baseline : 0 1.4 °1.2-1.7 0.2 5
2' of Exposure
15" Post Exposure
30" Post Exposure

DAY 4: Baseline no exposure
2' of Exposure
15" Post Exposure
30" Post Exposure

DAY 5: Baseline no exposure
2' of Exposure
15" Post Exposure
30" Post Exposure

63
''TABLE XXVII
PCE BREATH CONCENTRATIONS

WEEK: 10 (Alcohol, 1.5 ml/kg)

 

 

PCE CHAMBER PCE BREATH CONC., PPM NO.OF
TIME OF SAMPLE CONC., PPM MEAN RANGE +8 .D. SUBJECTS
MALES
DAY 1: Baseline 0
2' of Exposure
15" Post Exposure
30" Post Exposure
DAY 2: Baseline 0
2' of Exposure
15" Post Exposure
30" Post Exposure
DAY 3: Baseline. 100
2' of Exposure 30.0 25.0-34.2 4.7 3
15" Post Exposure L563 11.0-19.7 3.6 4
30" Post Exposure 1261 7.6-14.9 4.0 3
DAY 4: Baseline 25 3.4 2025.02 1.4 4
2' of Exposure 11.5 11.0-12.3 0.6 4
15" Post Exposure 7.9 6.8-8.9 0.9 4
30" Post Exposure 6.7 6.5-6.8 0.2 3
DAY 5: Baseline 100 2.3 1.6-3.0 0.7 3
2' of Exposure 335 26.5=37.0 6.1 3
15" Post Exposure 17.9 16.5-19.1 1.3 3
30" Post Exposure 13,3 10.4-18.0 4.1 3
FEMALES
DAY 1: Baseline 0
2" of Exposure
15" Post Exposure
30" Post Exposure
DAY 2: Baseline 0
2‘ of Exposure
15" Post Exposure
30" Post Exposure
DAY 3: Baseline 100
2' of Exposure 28.5 28.6-32.3 323 5
15" Post Exposure 15.8 14.5-17.1 1.0 5
30" Post Exposure 11.6 9.6-13.5 1.4 5
DAY 4: Baseline 25 4.1 3.4-5.2 0.8 4
2" of Exposure 10.0 8.2-11.6 1.2 5
15" Post Exposure 6.8 5.5-8.2 Asods 5
30" Post Exposure 58 4.8-6.5 0.7 5
DAY 5: Baseline 100 2.9 2.7-3.3 0.3 4
2' of Exposure 30.5 27.5-33.5 255 5
15" Post Exposure 75 14.7-21.8 301. 5
30" Post Exposure 12.9 9.8-14.7 1.8 5

64
''DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

TIME OF SAMPLE

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Base line

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline,

2' of Exposure
15"" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30"' Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30"" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

TABLE XXVIII
PCE BREATH CONCENTRATIONS

WEEK: 11 (Valium, 6 mg)

 

PCE CHAMBER PCE BREATH CONC., PPM NO. OF
CONC. , PPM MEAN RANGE +8.D. SUBJECTS
MALES
0 24 1.7-2.9 0.6 3
0
100
8201. 31.1-32.4 0.7 4
17:7 13.0-20.0 363 4
16.2 12.7-18.4 25D 4
25 3.3 2.4-3.9 0.8 3
11.3 10.4-12.6 0.9
6.1 5.8-6.7 0.6 4
6.1 4.3-7.5 Ls3 4
100 3.8 3.2-4.3 0.8 2
41.3 33.3-49.3 11.3 2
17.7 17.3-18.0 0.5 2
16.8 16.0-17.5 1.1 2,
FEMALES
0 220 1.7-2.7 0.4 4
0
100
36.0 35.1-37.8 1.6 3
21.3 20.3-21.9 0.9 3
18.6 18.4-18.9 0.3 3
25 3.3 2.6-4.1 0.8 3
10.4 9.3-11.2 0.8 4
7.0 4.5-8.3 1.7 4
6.4 4.3-7.5 1.4 4
100 3.0 3.2-4.0 0.4 4
38.0 30.0-45.3 6.3 4
18.6 12.7-21.0 4.0 4
Lied 12.3-20.7 3.6 4

65
''DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

DAY

TIME OF SAMPLE

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline,

2" of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

Baseline

2' of Exposure
15" Post Exposure
30" Post Exposure

TABLE XXIX
PCE BREATH CONCENTRATIONS

WEEK: 12 (Control)

 

PCE CHAMBER PCE BREATH CONC., PPM NO. OF
CONC. , PPM MEAN RANGE +S.D. SUBJECTS
MALES
100 3.09 3.6-4.1 0.3 3
36.6 32.0-39.5 4.1 3
23.5 18. 2-28.3 Swl 3 5

16.9 13.9-22.4 4.8 3

0 309 3.4-4.3 0.5 3

0 2.3 1.4=3.1 0.9 3
25

11.4 10.2-13.6 L6 4

6.5 5.4-8.9 1.6 4

6.1 §.3-7.2 0.9 4

100 2.3 1.8-2.7 0.4 4

41.5 35.7-46.3 5.2 4

25.7 20.4-29.0 309 4

20.5 14.9-25.9 4.6 4

FEMALES

100 4.1 3.7-4.3 0.3 4

35.2 34.1-37.9 1.8 4

22.2 19.2-24.8 255 4

18.2 13¢9=21,.1 3.1 4

0 3.7 3.4-3.8 0.2 4

0 3.1 2.6-3.4 0.4 3
25

9.9 6.4-11.6 2.4 4

6.2 3.8-8.3 1.9 4

5.7 4.5-7.1 dd 4

100 2.4 1.8-2.9 0.6 3

37.0 31.4-40.4 3.9 4

22) 01. 16.5-28.6 5.0 2

18.4 10.0-23.9 6.9 5

66
''PCE CHAMBER

DAY OF WEEK CONC.,

PPM

 

ETHANOL BLOOD* CONCENTRATIONS

TABLE XXX

 

Dose: Approximately 0.75 ml vodka/kg body

100
25
100

OAPwNnd Fe

100
25
100

MP wnre

Dose: Approximately 1.5 ml

100
25
100

MWPwWN FE

100
25
100

We wWwnd Fe

ETHANOL BLOOD CONC., mg/dl NO. OF

MEAN RANGE £6 Dis SUBJECTS

WEEK 5

weight

MALES
35.6 28.5-42.5 D wAL 5
50.6 31.7-64.3 13.8 4
44.1 25.5-56.4 11.5 5
50.0 41.0-63.2 9.1 5
50.7 39.2-59.1 8.4, 5

FEMALES
32.1 13.6-42.1 10.9 5
48.5 33.7-58.6 Vd... 2 4
43.1 20.7-56.9 14.5 5
54.8 45.9-64.9 8.0 4
46.8 23.9-60.3 15.0 5

WEEK 10

vodka/kg body weight

MALES
62.6 40.0-90.5 20.8 4
51.7 44.6-58.4 6.2 4
58.8 44.1-66.1 10.0 4
65.5 54.0-81.0 13.2 4
69.2 65.0-72.0 347 3

FEMALES
63.3 41.1-85.5 15.9 5
64.1 44.0-74.1 12.6 5
54.2 36.8-71.4 15.0 5
74.4 34.0-105.0 26.7 5
701 47.5-95.0 21.8 5

*Sampled 15-20 min after dosage that was consumed over

67

30-min period
''ETHANOL BREATH* CONCENTRATIONS

PCE CHAMBER
DAY OF WEEK CONC. , PPM

 

Dose: Approximately 0.75 ml vodka/kg body weight

100
25
100

WAR whrd

100
25
100

WE wn eR

Dose: Approximately 1.5

100
25
100

ONAREwWwNn ke

100
25
100

WOPwWwWNnN ke

ETHANOL BREATH CONC., PPM

TABLE XXXI

 

MEAN RANGE +S .D:
WEEK 5
MALES
130 102-154 26
181 144-245 48
153 118-181 2
156 130-180 23
156 106-200 38
FEMALES
118 82-170 41
136 125-147 10
134 75-200 62
198 160-270 63
148 96-192 48
WEEK 10
ml vodka/kg body weight
MALES
209 162-255 38
241 201-313 50
218 206-247 20
250 202-304 43
194 160-226 33
FEMALES
341 240-465 lll
335 262-480 85
277 182-352 71
279 223-324 41
213 173-246 30

NO. OF
SUBJECTS

ANPP Pw

WHwr Hf

woke LS

FOO

*Sampled 15-20 min after dosage that was consumed over 30-min period

68
''TABLE XXXII

DIAZEPAM BLOOD* CONCENTRATIONS

 

 

PCE CHAMBER DIAZEPAM BLOOD CONC., ug/dl NO. OF
DAY OF WEEK CONC., PPM MEAN RANGE +8.D. SUBJECTS
WEEK 3

Dose: 6 mg/day (2 mg t.i.d.)

MALES
1 0 12 9-16 2.9 6
2 0 19 14-25 3.8 6
3 100 19 14-24 4.7 6
4 25 25 20-32 4.5 6
5 100 24 21-29 2.9 6
FEMALES
1 0 12 9-17 2ad 6
2 0 L7 14-22 2.8 6
3 100 17 13-21 2.9 6
4 25 21 20-22 0.6 6
5 100 21 16-27 3.7 6
WEEK 4
Dose: Placebo
MALES
1 0 <5 ik 4
2 0 <5 1
3 100 <5 2
4 25 <5 1
D 100 <5 1
FEMALES
1 0 <5 6
2 0 <5 3
3 100 <5 2
4 25 <5 J.
5 100 a5 2

*Sampled approximately 45 min after second dose
**Detection limit = 5 yg/dl

69
''TABLE XXXIIT

DIAZEPAM BLOOD* CONCENTRATIONS

 

 

PCE CHAMBER DIAZEPAM BLOOD CONC., ug/dl1 NO. OF
DAY OF WEEK CONC., PPM MEAN RANGE +$.D. SUBJECTS
WEEK 7

Dose: 10 mg/day (5 mg b.i.d.)

MALES
1 0 19 17-21 1.7 4
2 0 13 10-18 3.6 4
3 100 18 14-21 3.5 3
4 25 21 11-41 13.5 4
5 100 30 20-42 9.3 4
FEMALES
1 0 16 12-23 4.4 5
2 0 13 8-19 4.2 5
3 100 19 14-28 4.6 5
4 25 17 9-26 6.2 5
5 100 23 13-30 6.3 5
WEEK 8
Dose: Placebo
MALES
1 0 ——
2 0 <5** 2
3 100 <5 2
4 25 <5 2
5 100 <5 1
FEMALES
1 0 <5 3
2 0 <5 2
3 100 <5 2
4 25 <5 1
5 100 --

*Sampled approximately 45 min after second dose

**kDetection limit = 5 ug/dl a
''TABLE XXXIV

DIAZEPAM BLOOD* CONCENTRATIONS

 

 

PCE CHAMBER DIAZEPAM BLOOD CONC., ug/dl NO. OF
DAY OF WEEK CONC., PPM MEAN RANGE +5.D. SUBJECTS
WEEK 11

Dose: 6 mg/day (2 mg t.i.d.)

MALES
1 0 8 6-9 1.4 4
2 0 12 11-14 1.5 3
3 100 1l 7-16 4.4 3
4 25 19 11-25 7.0 4
5 100 8 8-8 0.0 2

FEMALES
1 0 8 5-10 2d 4
2 0 15 11-20 3.3 5
3 100 12 9-15 3.0 3
4 25 13 8-18 4.1 4
5 100 16 10-20 4.2 4

WEEK 12
Dose: Control

MALES

1 0 <5x** 3
2 0
3 100 <5 1
4 25
5 100

FEMALES
1 0 <5 4
2 0 <5 1
3 100
4 25
5 100

*Sampled approximately 45 min after second dose
*kDetection limit = 5 ug/dl =
''cl

TABLE xxxv

ALCOHOL AND DIAZEPAM EFFECTS UPON PERCHLOROETHYLENE
BLOOD AND BREATH LEVELS, 5-1/2 HOUR EXPOSURE

 

 

 

 

 

 

 

 

 

 

PPM PCE in Blood PPM PCE in Breath
PCE in @ 2 hours into exposure @ 2 hours into exposure @ 30 minutes post exposure
Chamber, PCE PCE PCE b PCE PCE PCE PCE PCE PCE
PPM alone + alcohol? + diazepam alone + alcohol? + diazepam alone + alcohol? + diazepam
25 1.65 2.92%* 1.76 11.03 12.35* 11.72 6.40 7 .49%% 6.96%
(35) (15) (23) (35) (15) (23) (35) (14) (22)
100 8.25 7.96 8.47 33.2 32.3 35.5 17.62 13.83%* 17.35
(63) (29) (41) (68) (28) (44) (64) (29) (42)
a
Alcohol blood levels of 30 to 100 mg%

Diazepam blood levels of 7 to 30 mcg%

Significantly different from PCE alone at p<.05

kk

Significantly different from PCE alone at p<.0l

(n) Number of determinations

 
''WEEK

2

DAY

2

PCE,
PPM

0

25

100

o

100

25

100

100

25

100

OTHER

diazepam,
daily,
6 mg

placebo
daily

TABLE XXXVI

DEVIATIONS NOTED IN PERC/DRUG STUDY

GENERAL, BEHAVIORAL, NEUROLOGICAL, SUBJECTIVE, MEDICAL DEVIATIONS
General - all ss learning schedule. Medical - ssll7 and 329

have viral infections. Neurological - computer EEG program

not working.

Behavioral - all ss told to holdarms parallel to table in
Michigan eye-hand, mechanical problems with rotary pursuit and
dual-tasks tests. Neurological - no PM EEG tracings for s334.

Behavioral - saccade velocity test equipment problems.

Medical - s326 mildly nauseated in AM.

General - s327 tired.

Behavioral - s330 had difficulty during Flanagan Coordination
due to coughing. Subjective - s333 was clarified re. "check'!
questions on mood test.

General - physician noted altered mood in chamber. Behavioral -
staff operator noted problems with dual-attention task equipment.

General - s329 upset due to involvement in car accident pre-
vious PM. Behavioral - ss327, 330, and 334 rotary pursuit
tests invalid due to mechanical problems. Medical - s326
has URI.

Behavioral - still having problems with dual-tasks test.
Medical - ss330 & 333 have URI.

General - all testing started 40 min later than normal.
Behavioral - dual-task test equipment repaired. Neurological -
EEG computer program repaired. Medical - s327 sent home,

URI. 5329 not exposed due to medical problem.

General - all testing started 20 min later than normal.

Medical - s329 still held out from study resolving medical

problem.

Medical - s329 back in study.

(continued)

I
''WEEK

5

DAY

PCE,
PPM

100
25

100

100

25

100

100
25

100

°o

100

25

TABLE XXXVI (continued)

DEVIATIONS NOTED IN PERC/DRUG STUDY

 

 

OTHER GENERAL, BEHAVIORAL, NEUROLOGICAL, SUBJECTIVE, MEDICAL DEVIATIONS

alcohol, General - control day for s326. s331 called home on emergency

daily, (last day exposed).

0.75 ml

per kg General - last control day for s326. Medical - sll7 sent home
due to flu-like symptoms. Behavioral - s329 given second
saccade velocity test.
Medical - s327 has URI.

-- Behavioral - ss95, 327, and 332 rotary pursuit mechanical

problems. Medical - s327 has soft tissue bruise on leg,
s334 GI problems.

-- Behavioral - rotary pursuit data all invalid.

= Medical - s334 held out of study due to medical problem.

-- Medical - s334 held out of study due to medical problem.

-- Medical - s334 had medical problem resolved, back in study.
diazepam, General - sll7 ingested 2 beers prior to coming to work, all
daily, data invalid.

10 mg
Subjective - ss all seem tired and subdued.
Behavioral - rotary pursuit data for s327 invalid.
Behavioral - dual tasks test data invalid for s95.
General - s123 withdrawn from study because of unexcused
absences. Medical - s330 taken out of chamber at 1.5 hr due
to nausea.

placebo, --

daily

Medical - s332 has URI.

Neurological - ss may have noted accidental blinking of strobe
light during EEG. Medical - ss95, 330, 332 have cough or
sore throat.

Neurological - ss328 and 330 reported light flash during EEG,

corrected today.
(continued)

74
''WEEK

8

10

11

12

DAY

5

TABLE XXXVI (continued)

DEVIATIONS NOTED IN PERC/DRUG STUDY

 

 

PCE,
PPM OTHER GENERAL, BEHAVIORAL, NEUROLOGICAL, SUBJECTIVE, MEDICAL DEVIATIONS
100 Medical - s330 has URI.

25 -- Medical - s328 has some "flu -like" symptoms.

0 - Behavioral - s334 had finger injury and tetanus shot, therefore,
Flanagan coordination, rotary pursuit, Michigan eye-hand data
invalid. Medical - s330 has URI.

0 -- Behavioral - s1l7 repeated rotary pursuit test.

holiday
holiday
0 alcohol, --
daily,
0 1.5 ml --
per kg
100 --
25 --
100 Behavioral - s329 had invalid rotary pursuit test.
0 diazepam, Subjective - s330 upset due to multiple sticks upon blood with-
daily, drawal. Medical - s333 has URI.
6 ng
0 General - s332 entered study 40 min late, all data invalid.
100 --
25 --
100 Behavioral - s330 Flanagan coordination invalid. Subjective -
all mood tests invalid due to random answering w/o pseudonyms.
100 -- General - all ss entered chamber 15 min later than normal.

0 — me

0 - General - s333 entered chamber 20 min late.

25 -- General - all ss received debriefing in PM - s333 entered chamber
15 min late.
100 -- Behavioral - all rotary pursuit data probably invalid due to

mechanical difficulties.

75
''TABLE XXXVIT

MOOD ASSESSMENT CONTEXT ARRANGED IN NINE GROUPS

DEPRESSS ION

sad
downhearted
worthless
unhappy
useless
depressed
blue
troubled
lonely

HOSTILITY

angry
irritable
annoyed
rude
sarcastic

COGNITIVE GAIN

confused

able to think clearly
forgetful

able to concentrate
alert

ACCORDING TO DAVIS(1971)

CAREFREE

happy
full of pep

carefree
at ease
active
cheerful
satisfied
lively
efficient

ANXIETY

tense

on edge
fearful
impatient
restless
nervous
jittery

GUILTY-ASHAMED
troubled by conscience

sorry for things done
weary

76

FRIENDLINESS

goodnatured
friendly
kind
warmhearted
pleasant
considerate

MISCELLANEOUS

suspicious

feel sexy

need a cigarette
need a drink

taken advantage of
hungry

headache

stomach upset
trouble seeing

FATIGUED

tired
sleepy
worn out
''LL

EFFECT OF PCE AND DIAZEPAM UPON SUBJECTIVE SYMPTOMS AND PCE ODOR PERCEPTION

TABLE XXXVIII

MEAN PER SUBJECT REPORT

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PCE Conc, ppm 0 25 100 25 100 25 100 0 25 100

Drug Dose, mg/day 0 0 0 Plac | Plac | Plac 6 6 10 10 10

No. of Subject Reports 71 35 46 35 19 + 38 40 20 37 18 9 16

SYMPTOM Mean Number Per Subject Report

HEADACHE incidence 0.14 | 0.11 | 0.09 | 0.20 | 0.11 | 0.08 | 0.05 | 0.05} 0.08 | 0.06 | 0.11 | 0.06
persistence 0.42 | 0.34 | 0.09 | 0.43 | 0.21 | 0.08 | 0.13 | 0.05} 0.30 | 0.06 | 0.11 0.06

NAUSEA incidence 0.03 | 0.03 | 0.09 | 0.0 0.05 | 0.0 0.0 0.0 0.03 | 0.06 | 0.11 | 0.13
persistence 0.07 | 0.03 | 0.28 0.11 0.05 | 0.28 | 0.22 | 0.38

DIZZINESS incidence 0.01 | 0.06 | 0.07 | 0.03 | 0.05 | 0.05} 0.05 } 0.0 0.03 | 0.06 | 0.22 | 0.13
persistence 0.01 | 0.14 | 0.07 | 0.03 | 0.11 | 0.16] 0.10 0.11 | 0.06 | 0.44 | 0.50

CHEST PAIN incidence 0.03 | 0.03 | 0.02 | 0.06 | 0.0 0.0 0.03 | 0.05} 0.03 | 0.0 0.0 0.0
persistence 0.10 0.06 0.15 0.31 0.18 0.40 0.22

ABDOM. PAIN incidence 0.0 0.03 | 0.07 | 0.14 | 0.11 | 0.03 | 0.05 | 0.0 0.03 | 0.06} 0.0 0.0
persistence 0.23 0.28 | 0.46 0.11 0.13 0.40 0.08 0.44

ENT IRRIT. incidence 0.42 | 0.49 | 0.35 | 0.34 | 0.26] 0.37] 0.30 | 0.45] 0.38 | 0.28] 0.33] 0.31
persistence 1.93 | 2.11 | 1.91 | 1.80 |] 1.16] 1.89 1.05 | 0.50: 1.73 | 0.72 | 0.89 1.06

OTHER incidence 0.28 | 0.37 | 0.24] 0.43 | 0.42 | 0.34] 0.35 | 0.40} 0.32 |] 0.44] 0.56 0.56
persistence 1.06 | 1.51 | 0.83 | 1.54] 1.47] 0.97 1.35 1.50} 1.05 | 2.00] 2.00] 2.13

ODOR

MILD incidence 0.21 | 0.66 | 0.59] 0.17 | 0.79] 0.55] 0.15 | 0.80] 0.57 | 0.06} 0.67 0.44
persistence 0.44 | 1.71 | 1.67] 0.26} 1.47 2.00] 0.28 | 1.85} 1.68 | 0.17 1.33 | 1.31

MODERATE incidence 0.03 | 0.60 | 0.65] 0.0 0.26} 0.47] 0.0 0.35] 0.70} 0.06] 0.22] 0.56
persistence 0.04 | 0.89 | 1.15 0.26 | 1.08 0.50} 1.97] 0.06] 1.22] 0.63

STRONG incidence 0.01 | 0.20 | 0.48] 0.0 0.16} 0.61] 0.0 0:05] 0.57 ] 0.0 0.11 | 0.50
persistence 0.01 | 0.26 | 0.98 0.16} 0.89 0.10] 0.68 0.11 1.06

 

 

 

 

 

 

 

 

 
''82

EFFECT OF PCE AND ALCOHOL UPON SUBJECTIVE SYMPTOMS AND PCE ODOR PERCEPTION

TABLE :XXXIX

MEAN PER SUBJECT REPORT

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PCE Conc, ppm 0 25 100 0 25 100 0 25 100

Alcohol Dose, ca. ml/kg 0 0 0 0.75 | 0.75 | 0.75 | 1.5 125 15.5

No. of Subject Reports 71 35 46 19 9 20 17 9 17

SYMPTOM Mean Number Per Subject Report

HEADACHE incidence 0.14 | 0.11 | 0.09 | 0.26 | 0.11 | 0.10 | 0.24 | 0.11 | 0.06
persistence 0.42 | 0.34 | 0.09 { 1.05 | 0.22 | 0.10 | 0.53 | 0.33 | 0.12

NAUSEA incidence 0.03 | 0.03 | 0.09 | 0.05 | 0.22 | 0.15 | 0.06 | 0.0 0.0
persistence 0.07 0.03 0.28 0.05 0.67 0.80 0.18

DIZZINESS incidence 0.01 | 0.06 | 0.07 | 0.0 0.22 | 0.05 | 0.0 0.0 0.0
persistence 0.01 | 0.14 | 0.07 0.33 | 0.10

CHEST PAIN incidence 0.03 0.03 0.02 0.0 0.0 0.0 0.0 0.0 0.0
persistence 0.10 | 0.06 | 0.15

ABDOM. PAIN incidence 0.0 0.03 0.07 0.05 0.11 0.05 0.0 0.0 0.0
persistence 0.23 | 0.28 | 0.16 | 0.22 | 0.15

ENT IRRIT. incidence 0.42 0.49 0:35 0.42 0.22 0.40 0.24 0.33 0.47
persistence 1.93 2.11 1.91 fF 1.32 0.89 1.20 1.12 1.67 212

OTHER incidence 0.28 | 0.37 | 0.24] 0.21 | 0.44 | 0.35 | 0.41 | 0.33 | 0.47
persistence 1.06 | 1.51 | 0.83 | 1.05 | 1.22 | 1.30] 1.18 | 0.89 | 1.29

ODOR

MILD incidence 0.21 | 0.66 | 0.59 | 0.11 | 0.4@ 1 0.65 | 0.0 0.78 | 0.47
persistence 0.44 | 1.71 | 1.67] 0.21 | 1.22 | 1.70 1.22 | 1.29

MODERATE incidence 0.03 0.60 0.65 0.0 0.56 0.60 0.0 0.33 0.59
persistence 0.04 | 0.89 | 1.15 1.67 | 1.25 0.33 | 1.47

STRONG incidence 0.01 | 0.20 | 0.48] 0.0 0.0 0.45 | 0.0 0.22 | 0.47
persistence 0.01} 0.26 | 0.98 0.75 6.33 | 0.59

 

 
''TABLE XL

EFFECT OF PCE AND DIAZEPAM UPON STAFF ASSESSMENT
OF SUBJECTS' MOOD AND BEHAVIOR

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

6L

 

 

 

 

 

 

 

 

 

 

PCE Conc, ppm 0 25 100 0 25 100 . 0 25 100 0 25 100

Drug Dose, mg/day 0 0 0 Plac | Plac]| Plac 6 6 6 10 10 10

Days 6 3 4 4 2 4 2 1 3 2 i 2

DIMENSION

Alert 0.86 0.62 1.02 0.64 1..:63 1.06 0.82 0.83 0.97 §-1.00 | -1.00 | -0.24
Concentration 0.72 0.49 0.73 0.66 1.09 1.00 1.12 0.83 1.04 §-0.41 0.33 | =0.17
Happy 0.67 0.102 1.21 0.31 1.38 L. 12 0.21 1.33 1.36 f-0.61 | -0.67 | -0.25
At Ease 0.75 0.33 0.79 0.71 he 27 1.03 0.59 1.00 1.82 1.08 0.33 0.33
Friendly 0.97 0.30 0.77 0.65 1.34 L. dL 0.72 1.33 1.22 0.34 1.00 0..59
Carefree 0.72 O27 0.93 0.51 1.42 0.83 0.59 1.17 1.23 0.. 59 0.67 0.34
Full of Pep 0.18 0.33 0.40 | -0.56 1.05 0.13 |-0.34 0.0 -0.16 §-1.92 | -1.83 ] -1.75
Giddy -0.56 | -0.54 | -0.18] -1.01 0.57] -0.25 }-0.90 0.0 0.24 #-1.00 | -0.83 ] -1.34
Talkative 0.22 | -0.16 0.77} -0.68 1.20 0.63 |-0.68 1.00 0.55 {-1.50 | -1.00 ] -1.17
Active 0.19 0.21 0.564 -0.85 0.92 0.17 |-0.85 0.83 0.54 f-1.50 | -0.67 |] -1.25
Cooperative 0.59 0.37 0.87 0.94 0.84 0.80 0.94 0.67 1.07 0.25 0.33 0.67
In Balance 0.11 0.06 0.627 0.46 0.68 0.33 0.46 0.33 0.32 0.0 0.17 0.17

 

 

 

 

 

 

 

 

 

 

 

 

 

 
''08

TABLE XLI

EFFECT OF PCE AND ALCOHOL UPON STAFF ASSESSMENT

OF SUBJECTS' MOOD AND BEHAVIOR

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PCE Conc, ppm 0 25 100 0 25 100 0 25 100

Alcohol Dose, ca. ml/kg 0 0 0 -75 | 0.75] 0.75 | 1.5 1.5 1.5

Days 6 3 4 2 1 2 2 1 2

Alert 0.86 | 0.62 1.02 -67 0.80 a 1.04 0.50 1.41
Concentration 0.72 0.49 0.73 watz 0.80 0.83 } -0.34 0.0 1.10
Happy 0.67 | 0.02 | 1.21 -02 | 1.40 1.67 3.46 2.15 3.10
At Ease 0.75 | 0.33 | 0.79 -12 | 0.40] 1.00 2237 2.50 2.42
Friendly 0.97 | 0.30 | 0.77 -20 | 0.80 1.67 2.42 2.J9 2.81
Carefree 0.72 | 0.27 0.93 -98 | 0.60] 1.08 3,12 3.00 2.66
Full of Pep 0.18 | 0.33 |] 0.40 -48 | 0.20] 1.08 3.09 1.50 2.25
Giddy -0.56 | -0.54 |-0.18 -30 |-0.40] 0.42 2.87 1.50 L.. 95
Talkative 0.22 | -0.16 | 0.77 -97 | 0.40 1.33 3.42 3« 29 2.86
Active 0.19 0.21 | 0.56 -48 | 0.0 0.83 3.09 2.25 2298
Cooperative 0.59 | 0.37 | 0.87 -99 | 0.20] 0.83 7 0.72 1.25 1.27
In Balance O.11} 0.06 | 0.27 -19 [-0.20] 0.25 J -0.40 | -0.25 | -0.16

 

 

 

 

 

 

 

 

 

 

 
''ANALYSIS OF VARIANCE FOR A.M. MICHIGAN EYE-HAND COORDINATION TEST:

TABLE XLIL

PCE AND ALCOHOL

 

 

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE F-RATIO P-LEVEL
Total 220 4222.7027
Linear Day (adj.) 1 1651.7111 1651.7111 329.04643 <.005
Linear PCE (adj.) 1 .67672 -67672 -13481 ns
Linear Alcohol (adj.) 1 -59577 ~59577 - 11869 ns
Linear PCE x Linear Alc. 1L 13.17060 13.17060 2.62379 ns
People Effects 8 1512.4522 189.05652
Residual 208 1044.09644 5.01969

TABLE XLITI

ANALYSIS OF VARIANCE FOR P.M.

MICHIGAN EYE-HAND COORDINATION TEST:

PCE AND ALCOHOL

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE _F-RATIO P-LEVEL
Total 220 3837.4377

Linear Day (adj.) 1 1362.7621 1362.7621 243.85332 <.005
Linear PCE (adj.) 1 3.76556 3.76556 67381 ns
Linear Alcohol (adj.) 1 128.04042 128.04042 22.91162 <.005
Linear PCE x Linear Alc. 1 82714 82714 - 14801 ns
People Effects 8 1179.6459 147.45573

Residual 208 1162.39673 5.58845

 

 

81
''78

TABLE XLIV

RESULTS OF TREND ADJUSTED t-TESTS FOR EACH STUDY DAY

 

Day Exposure Level
No. PCE Diazepam Alcohol (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11)
1 0 0 0 ns ns ns ns ns ns 025 ns -005 -05 ns
2 0 0 0 ns -025 025 ns ns ns ns ns ns ns ns
3 25 0 0 ns ns ns ns ns ns ns ns ns ns ns
4 100 0 0 ns ns ns ns ns ns ns ns ns ns -05
7 0 6 0 ns -02 -001 ns ns ns ns ns ns ns ns
8 0 6 0 ns 05 02 ns ns us ns ns ns ns ns
9 100 6 0 ns ns ns ns ns ns ns ns ns ns ns
10 25 6 0 ns ns ns ns -05 ns ns ns 205 ns ns
11 100 6 0 305 ns ns ns ns ns ns -005 ns -O1 ns
14 0 P 0 ns ns ns ns -02 ns «02 ns ns ns ns
15 0 P 0 ns ns ns -005 -05 «025 ns ns ns 02 ns
16 100 P 0 ns ns ns ns ns -O1 ns ns ns -02 -05
7 25 P 0 ns O02 -001 ns -02 -001 ns ns -005 ns ns
18 100 P 0 -02 -005 -005 -05 Ol -02 05 *05 -02 ns ns
21 0 0 «75 -05 -05 ns ns ns ns ns ns ns ns ns
22 0 0 75 ns «02 ns ns ns ns ns ns ns ns ns
23 100 0 «75 ns -001 ns ns ns 05 ns ns ns ns ns
24 25 0 75 ns -005 ns ns ns ns ns ns ns ns ns
25 100 0 75 ns 05 ns ns ns ns -05 30S ns ns ns
28 100 0 0 ns ns ns ns ns ns ns ns ns ns ns
29 0 0 0 ns OL -005 ns ns ns ns ns ns -02 ns
30 0 0 0 ns 005 -02 ns -02 ns ns ns -005 ns ns
31 25 0 0 ns 005 01 ns ns ns ns -05 ns ns ns
32 100 0 0 ns -O1 -05 ns ns ns -005 ns ns 05 ns
35 0 10 0 ns ns ns -02 ns ns ns ns ns -05 «02
35 0 10 0 ns ns ns ns ns ns ns ns ns ns »025
37 100 10 0 ns ns ns ns ns ns ns ns ns ns -O1
38 25 10 0 ns ns -02 ns ns ns ns ns ns ns ns
39 100 10 0 -001 -05 ns ns ns ns ns ns ns ns ns

(continued)
''€8

Day Exposure Level

TABLE XLIV (continued)

‘RESULTS OF TREND ADJUSTED t-TESTS FOR EACH STUDY DAY

 

 

No. PCE Diazepam Alcohol (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11)
42 0 P 0 -05 ns ns ns ns ns ns ns ns ns ns
43 0 P 0 ns ns ns ns ns ns ns ns ns ns ns
44 100 P 0 ns OL ns ns ns ns ns ns ns ns ns
45 25 P 0 ns -005 ns ns 02 ns -05 ns 302 ns ns
46 100 P 0 ns 02 ns ns ns ns ns ns ns ns ns
49 25 0 0 ns ns ns ns ns ns ns ns ns 025 ns
50 0 0 0 ns ns ns ns ns ns ns ns ns ns ns
5k 0 0 0 ns ns ns ns ns ns ns ns ns ns ns
56 0 0 15 -005 ns .05 02 -O1 001 -005 -005 -005 ns #05
57 0 0 1.5 OL ns ns .025 -02 -005 -001 -025 .005 ns ns
58 100 0 125 -O1 ns -01 .005 oO1 -001 -005 -005 001 ns ns
59 25 0 1.5 ns ns ns 05 -02 001 .005 -05 -005 ns ns
60 100 0 1.5 -05 ns ns #05 -01 -005 -05 -05 -005 ns ns
63 0 6 0 ns ns ns ns ns ns ns ns ns 02 ns
64 0 6 0 ns ns ns ns -O1 ns ns ns OL ns ns
65 100 6 0 ns ns ns ns ns ns ns ns ns ns ns
66 25 6 0 ns ns ns ns -005 «01 ns ns ns ns ns
67 100 6 0 ns ns ns ns «O25 ns -005 ns -02 ns ns
70 100 0 0 ns ns ns ns ns ns ns ns ns ns ns
ral 0 0 0 ns ns ns ns ns ns ns ns ns ns ns
d2 0 0 0 ns -02 ns ns ns ns ns ns ns -05 ns
13 25 0 0 ns ns ns ns ns ns ns ns ns ns ns
74 100 0 0 ns ns ns ns ns ns ns ns -05 ns ns

.
(1) Flanagan Coordination (4) Time Off Target Rotary Pursuit 15 rpm (8) Errors Rotary Pursuit 15 rpm
(2) Michigan EH AM (Ss) *% " " 30 rpm (9) " " 30 rpm
(3) Michigan EH PM (6) ” " 45 rpm (10) " " 45 rpm
qy ™ " " 60 rpm (11) " " 60 rpm
''TABLE XLV

ANALYSIS OF VARIANCE FOR A.M. MICHIGAN EYE-HAND COORDINATION TEST: PCE AND DIAZEPAM

 

 

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE  F-RATIO F-LEVEL
Total 342 7849 .0203
Linear Day (adj.) 1 3120.5006 3120.5006 519.14551 <.005
Linear PCE (adj.) 1 6.55081 6.55081 1.08983 ns
Linear Diaz. (adj.) 1 17.76346 17.76346 2.95524 ns
Linear PCE x Linear Diaz. 1 6.13822 6.13822 1.02119 ns
(adj.)

People Effect , 8 2714.4892 339.3415
Residual 330 1983.57813 6.01084

TABLE XLVI

ANALYSIS OF VARIANCE FOR P.M. MICHIGAN EYE-HAND COORDINATION TEST: PCE AND DIAZEPAM

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE F-RATIO P-LEVEL

Total 342 6938.5674

Linear Day (adj.) 1 2818.4941 2818.4941 496.35094 <.005

Linear PCE (adj.) 1 2.24162 2.24162 -39476 ns

Linear Diaz. (adj.) 1 18.28790 18.28790 3.22059 ns

Linear PCE x Linear Diaz. 1 8.47979 8.47979 1.49333 ns
(adj.)

People Effects 8 221741813 271.14766

Residual 330 1873.88281 5.67845

 

 

84
''ANALYSIS OF VARIANCE FOR FLANAGAN COORDINATION TEST:

TABLE XLVII

PCE AND ALCOHOL

 

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE _F-RATIO P-LEVEL
Total 220 41425 .0000

(1)

Linear Day (adj.-) 1 239.3341 239.3341 2.6455 ns
Linear PCE (adj.) 1 754.0464 754.0464 8.3348  P<.005
Linear Alcohol (adj.) 1 3733.4705 3733.4705 41.2677 —P<.005
eee Day (adj.) 1 34.2222 34.2222 - 3782 ns
Linear PCE (adj.) 1 300.1192 300.1192 3.3173 ns
Linear Alcohol (adj.) 1 1649 .0425 1649.0425 18.2276 P<.005
L.PCE x L.Alc. 1 54.5122 54.5122 -6025 ns
People 8 17437.7052 2179.7131

Residual 208 18817.6602 90.4695

 

 

Note (1): Assumes Model with absence of PCE-Alcohol interaction.

Note (2): Assumes Model with PCE-Alcohol interaction.

85
''TABLE XLVIITI

ANALYSIS OF VARIANCE FOR FLANAGAN COORDINATION TEST:

PCE AND DIAZEPAM

 

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE  F-RATIO P-—LEVEL
Total 342 46231.0000

(1)

Linear Day (adj.) 1 305.2656 305.2656 -6395 P<.05
Linear PCE (adj.) 1 437.127 437.127 - 6436 P<.025
Linear Diaz. (adj.) 1 224.8434 224.8434 ~4172 ns
oo Day (adj.) 1 304.3750 304.3750 626 P< 05
Linear PCE (adj.) 1 231.1051 231.1051 ~512 P<.1
Linear Diaz. (adj.) 1 105.1256 105.1256 -598 ns
L.PCE x L.Diaz. (adj.) L 1.5345 1.5345 .023 ns
People 8 23353.8864 2919.2358

Residual 330 21712.7539 65.7962

 

 

Note (1): Assumes Model with absence of PCE-Diazepam interaction.

Note (2): Assumes Model with PCE-Diazepam interaction.

86
''ANALYSIS OF VARIANCE FOR 15 RPM ROTARY PURSUIT TEST:

TABLE XLIX

PCE AND ALCOHOL

 

 

 

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE  F-RATIO P-LEVEL
Total 220 324 «53203
Linear Day (adj.) I 1.19046 1.19046 1.62780 ns
Linear PCE (adj.) i. -47244 -47244 - 64600 ns
Linear Alcohol (adj.) 1 22.32041 22.32041 30.52030 <.005
Linear PCE x Linear Alc. 1 -00723 00723 -00989 ns

(adj.)
People Effects 8 148.42441 18.55305
Residual _ 2.08 152.4708 . 73133

TABLE L

ANALYSIS OF VARIANCE FOR

30 RPM ROTARY PURSUIT TEST:

PCE AND ALCOHOL

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE _F-RATIO P-LEVEL

Total 220 4241.2867

Linear Day (adj.) 1 196.84016 196.84016 29.93380 <.005

Linear PCE (adj.) 1 2.14730 2.14730 - 32654 ns

Linear Alcohol (adj.) 1 371.27166 371.27166 56.45987 <.005

Linear PCE x Linear Alc. 1 5.13211 5.13211 - 78045 ns
(adj .)

People Effects 8 2298.493 284.26491

Residual 208 1257 «77587 6.57585

 

87
''TABLE LI

ANALYSIS OF VARIANCE FOR 45 RPM ROTARY PURSUIT TEST: PCE AND ALCOHOL

 

 

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE F-RATIO P-LEVEL
Total 220 11060.588
Linear Day (adj.) 1 805.91894 805.91894 61.07094 <.005
Linear PCE (adj.) 1 8.18365 8.18365 -62014 ns
Linear Alcohol (adj.) 1 1156.1816 1156.1816 87.61314 ~.005
Linear PCE x Linear Alc. 1 11.15636 11.15636 84541 ns

(adj .)
People Effects 8 6334.2962 791.78627
Residual 208 2744.85938 13.19644

TABLE LII

ANALYSIS OF VARIANCE FOR 60 RPM ROTARY PURSUIT TEST: PCE AND ALCOHOL

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE  F-RATIO P-LEVEL

Total 220 11295.052

Linear Day (adj.) 1 641.15817 641.15817 42.93551 <.005

Linear PCE (adj.) 1 43.68820 43.68820 2.92560 ns

Linear Alcohol (adj.) 1 568.47365 568.47365 38.06815 <.005

Linear PCE x Linear Alc. 1 72.30947 72430947 4.84224 <.05
(adj.)

People Effects” 8 6862.3499 854.9579

Residual 208 3106.07422 74.93305

 

 

88
''ANALYSIS OF VARIANCE FOR 15 RPM ROTARY PURSUIT TEST:

TABLE LIIf

PCE AND DIAZEPAM

 

 

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE _F-RATIO P-LEVEL
Total 342 444.03199
Linear Day (adj.) 1 -97643 -97643 1.23036 ns
Linear PCE (adj.) 1 . 26965 . 26965 - 35313 ns
Linear Diaz. (adj.) 1 12.23945 12.23945 16.0284 <.005
Linear PCE x Linear Diaz. 1 04245 -04245 -05560 ns
(adj -)
People Effects 8 178.51413 22.31427
Residual 330 251.98988 0.76361
TABLE LIV
ANALYSIS OF VARIANCE FOR 30 RPM ROTARY PURSUIT TEST: PCE AND DIAZEPAM

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE _F-RATIO P-LEVEL

Total 342 3748.5687

Linear Day (adj.) 1 237.84305 237.84305 52.09664 <.005

Linear PCE (adj.) 1 8.57822 8.57822 1.87896 ns

Linear Diaz. (adj.) 1 11.09247 11.09247 2.42967 ns

Linear PCE x Linear Diaz. 1 7.61051 7.61051 1.66699 ns
(adj.)

People Effects 8 1976.8558 247.3397

Residual 330 1506.58889 4.56542

 

 

89
''TABLE LV

ANALYSIS OF VARIANCE FOR 45 RPM ROTARY PURSUIT TEST: PCE AND DIAZEPAM

 

 

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE F-RATIO P-LEVEL
Total 342 12874.242
Linear Day (adj.) L 1015.6076 1015.6076 94.65598 <.005
Linear PCE (adj.) 1 -69796 - 69796 -06505 ns
Linear Diaz. (adj.) 1 108.51152 108.51152 10.11342 <.005
Linear PCE x Linear Diaz. 1 2.42981 2.42981 - 22646 ns

(adj.)
People Effects 8 8206.2754 1025.7844
Residual 330 3540. 72266 10.72946

TABLE LVI

ANALYSIS OF VARIANCE FOR 60 RPM ROTARY PURSUIT: PCE AND DIAZEPAM

 

 

 

 

 

SOURCE DF SUM OF SQUARES MEAN SQUARE  F-RATIO P-LEVEL

Total 342 16055.508

Linear Day (adj.) 1 818.43684 818.43684 55.47987 <.005

Linear PCE (adj.) 1 37.45881 37.45881 2.53924 ns

Linear Diaz. (adj.) 1 129.83125 129.83125 8.80095 <.005

Linear PCE x Linear Diaz. 1 2.45736 2.45736 16658 ns
(adj.)

People Effects 8 10199.178 1274.8992

Residual 330 4868.14844

 

 

90
''SUBJECT

95

117

327

SUBJECT

328

329

330

332

333

334

LEAD 1

NS

NS

NS

LEAD 1

NS

NS

NS

NS

NS

NS

TABLE LVIIL

PCE-ETHANOL GROUP A

LEAD 2

NS

NS

NS

PCE-DIAZEPAM GROUP B

 

LEAD 2

NS
NS
NS
NS
NS

NS

2

91

RESULTS OF ANALYSIS OF VARIANCE FOR
DOMINANT FREQUENCY SHIFTS FOR EACH LEAD

LEAD 3
NS
NS

NS

LEAD 3

NS

NS

NS

NS

NS

NS

LEAD 4

NS

NS

NS

LEAD

NS

NS

NS

NS

NS

P<

-005
''SUBJECT

95

117

327

TABLE LVIIT
RESULTS OF ANALYSIS OF VARIANCE FOR PERCENT RELATIVE

ACTIVITY AT DIFFERENT TREATMENT CONDITIONS FOR FOUR
FREQUENCY BANDS AND AT EACH OF FOUR LEADS

PCE-ETHANOL GROUP A

BAND LEAD 1 LEAD 2 LEAD 3 LEAD 4
8 NS NS NS NS
0 NS NS NS NS
at NS P<.005 NS NS
B NS NS NS NS
8 NS NS NS NS
8 NS NS NS NS
a NS NS NS NS
B NS NS NS NS
5 NS NS NS NS
0 NS NS NS NS
at NS NS NS NS
B NS NS NS NS

92
''TABLE LIX
RESULTS OF ANALYSIS OF VARIANCE FOR PERCENT RELATIVE

ACTIVITY AT DIFFERENT TREATMENT CONDITIONS FOR FOUR
FREQUENCY BANDS AND AT EACH OF FOUR LEADS

PCE-DIAZEPAM GROUP B

 

SUBJECT BAND LEAD 1 LEAD 2 LEAD 3 LEAD 4

328 5 NS NS NS NS

8 NS NS NS NS

a NS NS NS NS

B P<.O1 NS NS NS
329 ) NS NS NS NS

8 NS NS NS NS

a NS NS NS NS

B NS NS NS NS
330 § NS NS NS NS

0 NS NS NS NS

O. NS NS NS NS

B NS NS NS NS
332 6 NS NS NS NS

98 NS NS NS P<.005

a NS NS NS NS

B P<.O1 P<.005 NS P<.01
333 ) NS NS NS NS

8 NS NS NS NS

a. NS NS NS NS

B P<. Ol NS NS NS
334 6 NS NS NS NS

8 P<.005 NS P<.005 NS

o. NS NS NS NS

8B NS NS NS NS

93
''SUBJECT

328

332

333

334

TABLE LX

TREATMENT CONDITIONS SIGNIFICANTLY DIFFERENT

FROM CONTROL FOR GROUP B SUBJECTS

B

a
RD

FRE NNH RR
_ we ee ee
RBBWDTDBWDBDBWD

v

—_——
ow ala
Oooooed WwW

ve

FHP PPwwwr

wv.

Dom.
Dom.
Dom.
Dom.
Dom.

Freq.
Freq.
Freq.
Freq.
Freq.

ACTIVITY

+> 35> ep HOO >>

>>

<< << 4+ 4€ 4+ 4 >

94

 

TREATMENT CONDITIONS
LO PCE — HI DIAZEPAM
HI PCE - HI DIAZEPAM
LO PCE - LO DIAZEPAM
HI PCE - HI DIAZEPAM
HI PCE —- HI DIAZEPAM
LO PCE - LO DIAZEPAM
HI PCE - HI DIAZEPAM
LO PCE - HI DIAZEPAM
HI DIAZEPAM
HI PCE — HI DIAZEPAM
HI DIAZEPAM
HI PCE - PLACEBO
LO PCE — HI DIAZEPAM
LO PCE - HI DIAZEPAM
HI PCE - LO DIAZEPAM
HI PCE - HI DIAZEPAM
HI PCE
HI DIAZEPAM
LO PCE - HI DIAZEPAM
HI PCE - LO DIAZEPAM
HI PCE - HI DIAZEPAM
''Y

eo

INN 1 |

 

 

Figure 1 : MICHIGAN EYE-HAND COORDINATION TEST

95
'' 

TEST 1

Figure 2: FLANAGAN COORDINATION TEST

96
'' 

 

Channel Lead

] F7-Ol1
2 F8-O2
3 F7-F8
4 F3-C3
5 F4-C4
6 C4-O2
7 C3-Ol

Figure 3: ELECTRODE GEOMETRY AND LEAD CONFIGURATION

97
''nN
oO

|

DEPRESSION
PE ELIETLLLLTELLLLLLL

wm

oO

Diazepam

Alcohol

PCE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

iin

-———4

 

 

 

 

 

 

 

 

HH

rele
mL TUL Un

 

 

 

 

 

  

 

 

 

 

 

 

VALIUM
10mg
&m9 Placebo Placebo 6mg
ALCOHOL
(mi /kg)
100 sesabOppma WM
[Lf] ny
renner ere erry wp “Tl” |
10 , 6 65 70

 
 

DAYS

Figure 4. SUBJECTS' MOOD ASSESSMENT: DEPRESSION
Daily mean scores(+ one SD). Circled dots represent

zero exposure days and the straight line represents
the trend of scores for these days while the outside
line(s) represent the 95% confidence limits.

98
'' 

I

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

r | T - Ty
—_— J
— f
osama $ .
1S— |
— | [ l 4 r
sini l »
ne} _—
ce —
i 10—
a =] bp [*
oO — . / L
h
- i
_“ L & ae |
— l
— L L
o—
VALIUM
0
Diazepam | éms | Placebo iii Placebo | ema |
ALCOHOL
Alcohol een [75 ] __ 50
100 — 100 ppm—
pee |_eJ] Tif] UA MM) ese [Ll] MM)
TTT PEee reer p eer ep re rg Teepe ripe erty erery rev epee ny Perper pe
5 10 18 20 25 30 35 40 45 50 55 60 65 70 7
DAYS
Figure 5. SUBJECTS'MOOD ASSESSMENT: CAREFREE

See Figure 4 for legend.

99

 
'' 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

20—
<a .
—_— r
is .. [ [ Lt
ware ~
”Y — ' .
WY __] r
uw
= —s d
= 10
S 7)
uJ 1 q
_ —o
wm
we —— | l | l
— . .
5
S— — L l ——
— | { i
o—
VALIUM
Diazepam | emo | Placebo eng Placebo [emo]
yee ‘
1.5
Alcohol ea ==
100-—] -——-100ppm—
poe [asd] MM UU To TT econ ML td
7 ee eee ee a ‘T! el ae ot ob
5 10 1S 40 45
DAYS

Figure 6. SUBJECTS' MOOD ASSESSMENT: FRIENDLINESS
See Figure 4 for legend.

100

 
'' 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

20—
is—
> _
= 10—
=
5
oO 4
— T T
Ss in
= Thc dl rly He | | Ht
aaa! +t fa I
oo ACCC Ait
Diazepam _ ane] Placebo ——e Placebo _
Alcohol ena (es) — {
roe (fl UT A) ee

DAYS

Figure 7. SUBJECTS! MOOD ASSESSMENT: HOSTILITY
See Figure 4 for legend.

101
'' 

20—

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

<
E so
> |
« 7 .
_ df I
Se AE
- il ll 4 Lal | re
= th tf
UTTER ait
Diazepam "Ee Placebo rel piaceo __ _
Alcohol Linh Ls] — er
pce Lill MO eee ll] TN
tb bh oh lll lle
DAYS

Figure 8, SUBJECTS' MOOD ASSESSMENT: ANXIETY
See Figure 4 for legend.

102
'' 

20-4

1S

MISCELLANEOUS
oO

Litt ttt ited tet te et td

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

: Tr
Tt ] : 1
S | r _*
7 | | [ {
| 4 1
. u Ape LL 7 A l tl f L
. — . Ls
L 5 L L L 7 = C aS
o— L [
VALIUM ——
Diazepam 6™9} Placebo te Placebo
ALCOHOL
k
Alcohol imi fio) — ce
‘esd | (Ll ] —-—100ppm —
PCE ih J LL! Fi na zseon || [LI | |
ie elt TA WD Ue ' poetry Tre vlue Vitepirae ieee att cee
10 20 4 35 vs i J a ab ! I 4
DAYS

Figure 9. SUBJECTS' MOOD ASSESSMENT: MISCELLANEOUS
See Figure 4 for legend.

103
'' 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

20—
a
is
zz
rear —
jen soe
oO
a] —
> 10-4
be —
_
5 — r . TI. .
ao _ alr = =
oO _| f au Ait Lilt Ur fat at
q Ht
Ss H at Hit TY tt 4
= | J ! : L L [
_| l ~ he | L b
_ I
o—
VALIUM
Diazepam [emo] Placebo 0m) racebo
ALCOHOL
(mi /kg) 138
Alcohol <n
ell MM) A Thi CL TU sen
Poe el Me
ee be PP Pree perep repre rey ee i
10 1S 30 40 45 50 55 60 65 4
DAYS

Figure 10. SUBJECTS! MOOD ASSESSMENT: COGNITIVE GAIN
See Figure 4 for legend.

104
'' 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

20—
1sS—
Gd
c
a aioe
—_
. 10—
coe
ss
Sf
a _]
5] .
=] re " i] : Citr r . .
_I -—+ tT stir tir tt ri T 4|
ool ECCS PU eat
VALIUM
Diazepam 6mG{ Placebo rome Placedo | mg |
ALCOHOL
Alpealrol ita —_
100 aoweoe m—
vcs iL i eeD Hid
! L I OS Z te fie a as
~—

Figure 11, SUBJECTS! MOOD ASSESSMENT: GUILT -ASHAMED
SEE Figure 4 for legend.

105
'' 

20—

1S

FATIGUE
o

S

—
—
ony
—
—
—
|
—— +
—
——-|
—o

0

Diazepam

Alcohol

 

PCE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

et

 

 

 

 

 

 

 

 

 

 

 

A iH

10mg

 

 

 

 

Placebo

 

PTT TT
20

 

Ls]

 

 

 

 

 

 

 

 

L y

mm
4 35 Z 4 a 55
DAYS

HT J Ei = =100pom—
al On ee
25

Figure 12. SUBJECTS' MOOD ASSESSMENT: FATIGUE

See Figure 4 for legend.

106

 
''50

45

40

35

50

MICHIGAN EYE-HAND COORDINATION SCORE
=
a

40

35

Diaz-

epam

Alco-
hol

PCE

     
    

A.M. SCORES

P.M. SCORES

 

 

 

 

 

 

VALIUM
10mg
Placebo Placebo [emo
ALCOHOL
(mi/kg) 1.50

 

 

 

 

 

sed] [i] WN li Mu)
ill ‘il Waleed ills ee napreterspesom pee pomp erry ere cere rap Mf

35 40245
DAYS

Figure 13. MICHIGAN EYE-HAND COORDINATION TEST. Daily mean scores (+ one SD).
Trend lines refer only to zero level exposure conditions.

 

107
'' 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

100 +
95 4
ee
w =
mS |__—F
°
oO >
n
¢
z > =
So >
& 4—%
< TT
z
2 +|?
5
o
Z
S 604
=<
Zz
a 55 4
VALIUM
Diaz - 10m
epam [ems] Placebo *} placebo __ _
Rive a
= (mi /kg) 1.50
hol (75 ] —
pea | ere
PCE 25 Sam ll HI ] J]
TETTOCUTE OPE TT POO ar RETR TE eR Een eke he Pere ee pee ey
5 10 15 20. «25 30-35 4p, 45 50 55 60 65 70 75
D.
Figure 14. FLANAGAN COORDINATION TEST. Daily mean scores (+ one SD)

Open circles represent zero days. The straight line describes
the trend of scores only for non-exposure conditions and the
outer lines depict the area of expected mean scores under non-
exposure conditions (with 95% confidence).

108
''Ww
°
1

ND

.

wn
1

nN
o
1

-

.

wn
i

1.0 +

20 4

TIME OFF TARGET (SECONDS)

NUMBER OF ERRORS

TIME

OFF TARGET

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

NUMBER OF ERRORS

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

VALIUM

 

 

 

 

 

it | H Lt
| | At

 

 

 

 

ene [ema |
6m9] Placebo Placebo

 

 

ALCOHOL

(mi /kg)

 

1.50

 

 

 

 

71 OM UO Do

TT DS bh lh

 

Figure 1

10 15 45 50 55 60 65 $70 75
DAYS
5. 15 RPM ROTARY PURSUIT TEST

109
'' 

 

 

TIME OFF TARGET
154
a
g
Oo
oO
BA
2 104
H
wa
Oo
x
<
H
i 54
oO
-
HH
0-4

nN NUMBER OF ERRORS

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

50 - p-—— ,
oO

40 4 4

oa +S
@

es yf
rs =
B 304 o ¢
4
fal |
é UW

20 + i——~

10 4
oe VALIUM

iaz-

10
epam [emo] Placebo ret piacebo __
Alco- AEOHOL
(mi/kg) .50
hol { 75 ] !
100

PCE

 

5 10 15 20 25 30 35 40 45 50 55 60 65 70 75

DAY
Figure 16, 30 RPM ROTARY PURSUIT TEST

 

110
'' 

   
  
  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

     

TIME OFF TARGET
a
g
oO
fa
Le
H
fa
oO
4
qt
H
fu
bu
oO
zi
H
°4
NUMBER OF ERRORS
80 4
754
70-
6574
n
6
6 60 54
fa
a 554
4
tf
é 505
45-4
40-5
355
307
Diaz- VALIUM
10mg
epam oma | Placebo Placebo
Aiesu ALCOHOL a
(ml/kg) 3
hol | 75 ]
100
PCE
5 10 15 20 25 30 35 40 45 50 55 60 65 70 78

  

 

DAY
Figure 17, 45 RPM ROTARY PURSUIT TEST

111
''TIME OFF TARGET (SECONDS)

95 4

90 +

55 4

50 4

Diaz-

epam

Alco-
hol

PCE

35
]
30 5
255
20 5
15 4

10 5

NUMBER OF ERRORS

~
oS

i

I

i

I

T

65 + iT]

 
    

TIME OFF TARGET

 

 

 

 

 

 

 

NUMBER OF ERRORS

 

o—

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

VALIUM

ene | emo |
&mg Placebo Placebo

ALCOHOL

(mt /kg) [7 ] 1.50
TS

100 — —100 ppm —

 

 

 

 

 

 

 

 

25 — 25ppm—

 

5 10 1S 20 25 30 Baye? 45 50 55 60 65 70 75

Figure 18. 60 RPM ROTARY PURSUIT TEST

112
''F7-01

THE EFFECT OF EXPOSURE TO PERCHLORCETHYLENE AND/OR
INGESTION OF ETHANOL ON THE ELECTROENCEPHALOGRAM

pce: 100 PPM PERCHLOROETHYLENE

LO ALCOHOL: ~0./75 ML/KG BODY WEIGH
HI ALCOHOL: ~1.50 ML/KG BODY WEIGHT
SUBJECT: #95

F8-02 F7-F8

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 19

- Pn

Be _ -
Se SS SS

=
o

 

CONTROL

HI ALCOHOL
+ PCE

HI ALCOHOL

LO ALCOHOL
+ PCE

LO ALCOHOL

PCE

CONTROL
''THE EFFECT OF EXPOSURE TO PERCHLOROETHYLENE AND/OR
INGESTION OF ETHANOL ON THE ELECTROENCEPHALOGRAM

pce: 100 PPM PERCHLOROETHYLENE

LO ALCOHOL: ~0,75 ML/KG BODY WEIGHT
HI ALCOHOL: ~],5Q ML/KG BODY WEIGHT
suBJECT: #117

F7-01 F8-02 : F7-F8

 

 

= phe = IR = Re > corr
= — IT . :acaio=s LS HI ALCOHOL
f = Pe A SS= rs
2, —————— > HI ALCOHOL
—— . x LO ALCOHOL
i + PCE

= > LO ALCOHOL

"%
~

_ Se CS= Sogo os

 

 

|
|

= CONTROL
meee eee wry

oo"

_ =>
T TT T TT T T T TT T [ Tt Trt T T TT T TT td
10 20 30 0 10 20 30
Hz Hz

10 20 30 O 10 20 30 0
Hz Hz

Figure 20
''THE EFFECT OF EXPOSURE TO PERCHLOROETHYLENE AND/OR
INGESTION OF ETHANOL ON THE ELECTROENCEPHALOGRAM

pce: 100 PPM PERCHLOROETHYLENE

LO ALCOHOL: ~ 0.75 ML/KG BODY WEIGHT
HI ALCOHOL: ~1,50 ML/KG BODY WEIGHT
SUBJECT: #123

 

F7-01 F8-02 F7-F8

CONTROL

|
|
|

HI ALCOHOL
+ PCE

pepovrered

rbrveuverdd

HI ALCOHOL

CTI
CUURT Reed

LO ALCOHOL

a
>
- - ens a > + PCE
<< ho  — Ss cee SS ————> LO ALCOHOL
iS

 

 

 

PCE
aN eee eT
_. = = 22 = CONTROL
{ ' ', ' J 1 t + { ' ct | Tt + ' ' ] t t ' { F ' ’ t T t T T T T Tt T T T o © T tc é i T T T T T J 1 Tt hT ]
0 10 20 30 0 10 20 30 0 10 20 30 0 10 20 30
Hz Hz Hz Hz

Figure 21
''THE EFFECT OF EXPOSURE TO PERCHLOROETHYLENE AND/OR
INGESTION OF ETHANOL ON THE ELECTROENCEPHALOGRAM

pce: 100 ppm PERCHLOROETHYLENE
LO ALCOHOL: ~ 0.75 ML/KG BODY WEIGHT

HI ALCOHOL: ~ 1.50 ML/KG BODY WEIGHT

9TT

:

F7-01

SUBJECT:

#326

|

| |

:

F8-02

\

)

pepecvtertavaegd

\

|
peur

‘

 

F3-C3

IIT

leaeuedl

 

Ww
oO
on

4
5s
+

-

—

4

4

4
on
of

_

—

om
4
4
~
4

Nd
o~
4
4

wo
om

CONTROL

HI ALCOHOL
+ PCE

HI ALCOHOL

LO ALCOHOL
+ PCE

LO ALCOHOL

PCE

CONTROL
''THE EFFECT OF EXPOSURE TO PERCHLOROETHYLENE AND/OR
INGESTION OF ETHANOL ON THE ELECTROI:NCEPHALOGRAM

pce: 100 PPM PERCHLOROETHYLENE

LO ALCOHOL: ~ 0.75 ML/KG BODY WEIGHT
HI ALCOHOL: 11.50 ML/KG BODY WEIGHT
SUBJECT: #527

 

F7-01 F8-02 F7-F8 F3-€3

 

 

CONTROL

HI ALCOHOL
+ PCE

HI ALCOHOL

LO ALCOHOL
+ PCE

LO ALCOHOL
PCE
mail _ 2 CONTROL
b* Pre | TP prep err ye"
0 10 20 30 0 10 20

Figure

23

 
''8TT

| |

1)

F7-0O1

|

THE EFFECT OF EXPOSURE TO PERC {LOROETHYLENE AND/OR
INGESTION OF ETHANOL ON THE ELECTROENCEPHALOGRAM

pce: 100 PPM PERCHLOROETHYLEN=

LO ALCOHOL: ~~ 0.75 ML/KG BODY W=IGHT
HI ALCOHOL: 11.50 ML/KG BODY W2IGHT
SUBJECT: #331

F8-02 £7-F8 F3-C3

7
|
ve pees
|
|

Vpydaeageataaeet
vilrsradaccehagdeal

VV VV NV”

|
viayaed

Ialyeaaly

 

 

4
—

4

=]

+
4
_—
°

4
Ro «x
}

a
we
oO
a=

4
pa
of
R=
5
Ww
wo

10 20 30

 

CONTROL

HI ALCOHOL
+ PCE

HI ALCOHOL

LO ALCOHOL
+ PCE

LO ALCOHOL

PCE

CONTROL
''THE EFFECT OF EXPOSURE TO PERCHLOROETHYLENF AND/OR
INGESTION OF DIAZEPAM ON THE ELECTROENCEPHALOGRAM

PcE: 100 PPM PERCHLOROETHYLENE
D(6): 6 MG/DAY

p(10): 10 mc/pDay

SUBJECT: #328

F7=-01 F8-02 F7-F8

— =
SS SS Ses

Se

 

 

 

_

 

 

 

 

 

ee a a a a | TOT TTT ye yy nee ype Ty
0 10 20 30 0 10 20 30 0 10 20 30

Hz Hz Hz

Figure 25

CONTROL
D(10) + PCE

D(10)

D(6) + PCE
D(6)

PLACEBO + PCE

PLACEBO

PCE

CONTROL
''F7-01

THE EFFECT OF EXPOSURE TO PERCHLOROETHYLENE AND/OR
INGESTION OF DIAZEPAM ON THE ELECTROENCEPHALOGRAM

pce: 100 PPM PERCHLOROETHYLENE
D(6): 6 MG/DAY

p(10): 10 me/pay

SUBJECT: #329

F8-02 F7-F8 F3-C€3

 

SS D(10) + PCE

—— Ne D(10)
SSS ees DIS
—_— ~ ——4 D(6) + PCE

7 as e. _ [> aes \
~~ LS >
eo —_— > PLACEBO + PCE

 

—~ ee > PLACEBO
- - SSS = SSS &
= PLS = ET. I? SSS; CONTROL
pec pee eg Typ Perper wpe) veep epee ee
0 10 20 30 O 10 20 30 0 10 20 30 0 10 20 30

Hz Hz Hz Hz

Figure 26
''THE EFFECT OF EXPOSURE TO PERCHLIROETHYLENE AND/OR
INGESTION OF DIAZEPAM ON THE ELECTROENCEPHALOGRAM

Pce: 100 PPM PERCHLOROETHYLENE
p(6):
| p(10):

SUBJECT:

6 MG/DAY
10 mG/pay

#330

F7=011. F8-02 F7-F8

- - SS
SS

 

 

 

 

 

 

 

 

 

Do —
“Ke —S =
—
oe ——————_—__— _ aA _ ——
= = :
Ss L Vy ancora —————
a HK — —

SS

 

i

 

 

OT a ree ote ey

0 10 20

Figure 27

 

CONTROL

D(10) + PCE

D(10)

D(6) + PCE

D(6)

PLACEBO + PCE

PLACEBO

PCE

CONTROL
''THE EFFECT OF EXPOSURE TO PERCHLOROETHYLENE AND/OR
INGESTION OF DIAZEPAM ON THE ELECTROENCEPHALOGRAM

Pce: 100 PPM PERCHLOROETHYLENE

p(6): 6 MG/DAY
p(10): 10 mc/pay
SUBJECT: #332
F7-01 F8-02 F7-F8

 

 

 

 

 

 

 

 

 

 

——__ >
‘a — = et Pon a
| =" ee
_ ~ — |
prep type ope ype epee prep eee yp per peeeyp ey
0 10 20 30 0 10 20 30 0 10 20 30 0 10 20 30
Hz Hz Hz Hz

Figure 28

 

CONTROL

D(10) + PCE

D(10)

D(6) + PCE

D(6)

PLACEBO + PCE

PLACEBO

PCE

CONTROL
''THE EFFECT OF EXPOSURE TO PERCHLOROETHYLENE AND/OR
INGESTION OF DIAZEPAM ON THE ELECTROENCEPHA!OGRAM

pce: 100 PPM PERCHLOROETHYLENE
p(6): 6 mG/DAY

p(10): 10 meé/pay

SUBJECT: #333

 

i z ~ => CONTROL
= 1 ——— ~~ PS > D(10) + PCE
lS SS =— 7 = —— LT, ———— D(10)
EX _ NS _ = ——— ——\\— ==
bs SS FE A neo ene
3 jgfe == SS - _ >

SSS Se SS a

PCE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

CONTROL

 

 

Figure 29
''F7-01

THE EFFECT OF EXPOSURE TO PERCHLOROETHYLENE AND/OR
INGESTION OF DIAZEPAM ON THE ELECTROENCEPHALOGRAM

PCE!
p(6):

p(10):

SUBJECT:

100 PPM PERCHLOROETHYLENE
6 MG/DAY
10 mG/Day

#334

F8-02

 

 

 

 

 

 

Hz

20

 

 

 

\

|

 

TET 3}, ] T T . I

30 0 10 20 30 0 10 20 30 0 10 20 30

Hz Hz
Figure 30

CONTROL
D(10) + PCE

D(10)

D(6) + PCE
D(6)

PLACEBO + PCE

PLACEBO

PCE

CONTROL
''7.

Date

APPENDIX I

INFORMED CONSENT QUESTIONNAIRE

Do you think the investigation is based on enough information to allow
the scientists to proceed safely, as explained, on human beings?

Yes No

Do you understand that you have the right to withdraw from the
investigation at any time?

Yes No

Do you consider this investigation to be useful:
- to yourself?

Yes No

- to your fellow men and women?

Yes No

Do you understand that other human beings have been exposed to the

same concentration of perchloroethylene for at least the same
period of time without showing any harmful effect?

Yes No

Do you understand that +;ou will be stuck with a needle a few times
a day on different days of the week in order that small samples of
blood can be drawn from you?

Yes No

Have the risks involved to you been adequately explained?

Yes No

Please tell us briefly why you are willing to participate in this investigation.

Signature

 

125
''APPENDIX II

MICHIGAN EYE-HAND COORDINATION TEST
INSTRUCT IONS~PROCEDURES

Determine if subject is left or right handed. Position plate
accordingly.

Instruct subject as follows:

a)

b)

d)

This is an eye-hand coordination test. There are 119 holes in
this maze from S to F. Your task is to insert the stylus tip

into each hole according to the traced pattern. Accuracy and

speed are important, and we record both. Any questions?

Again, let me remind you to be accurate if you miss a hole, or
deWiate from the pattern, we will have to start that trial
over. So accuracy is most important, and speed is second in
importance but do try to go as fast and as accurate as you can.

Ok - Put stylus in your right (or left hand), and place the tip
in the top hole marked S for start. TI will tell you when to
"start'. (Experimenter - resets clock to zero, and says 'start')

Experimenter records data for trial 1. Four trials are run per
session. No feed back on time values should be provided.
Appropriate encouragement can be given for those subjects

lacking in apparent enthusiasm. If errors are made, and you
instruct subject to start over, record this under the error
column on data sheet, and encourage subjects to be more accurate.
If they are really slow, encourage them to work faster.

Don't forget to date the data sheet.

126
''APPENDIX III

INSTRUCTIONS FOR
ROTARY PURSUIT

This is like a game. The area of white light is your target. The
object of the game is to keep this pointer on the target as much
of the time as possible when it goes around.

Chase the target in a circular motion if it gets away from you. Every-
time the tip of this pointer or stylus is not on the target an error

is scored.

Do not press down on the stylus; rather, follow the target with a

relaxed swinging movement of the arm. Also, relax your body to avoid
becoming tired.

Experimenter demonstrates.

You will be given one trial in which to warm-up. Then, you will be given
1 trial at 15 RPMs, 1 at 30 RPMs, 1 at 45 RPMs, and 1 at 60 RPMs with a

30 second rest period between each 45 second trial.

Any questions?

127
''Check the appropriate box - which indicates how you feel at

APPENDIX IVY

SUBJECTIVE FEELING INVENTORY

Use your first response.

FORM A

Some items just require you to follow directions.

 

10.
11.
12.
13.
14.
15.
16.
17.
18.
19.

20.

1. No Names
2.
that moment.
3.
Useless Not

Taken advantage of Not

 

Check "not at all" Not
Need a cigarette Not
Check "a little" Not
Sad Not
Nervous Not
Able to concentrate Not
Carefree Not
Fearful Not
Warmhearted Not
Cheerful Not
Alert Not
Restless Not
Feel sexy Not
Pati Sone Not
Pleasant Not
Need a drink Not
Check "Quite a

Bit Not
Efficient Not

at

at

at

at

at

at

at

at

at

at

at

at

at

at

at

at

at

at

at

at

all [|
all [|_|
all [_|
all [_}
all[_|
all |_|
all [_ |
all [|
all [|
all[ |
all |_|
all [|
all [_ |
all [_|
all [|
all[ |
211 [_|
all [_|
all [|
al1l[_|

128

little |]
little [|
little | |
little | |
little | |
little | |
little ||
little |] |
little | |
little [|
little | |
little | |
little | |
little | |
little [ |
little | |
little |_|
little | |
little [|
little | |

quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite

quite

a bit [ |
a bit | |
a bit] |
a bit] |
a bit] |
a bit] |
a bit] |
a bit | |
a bit] |
a bit |
a bit | |
a bit] |
a bit | |
a bit] |
a bit] |
a bit | |
a bit] |
a bit] |

a bit |

extremely LJ
extremely CI
extremely [J
extremely [J
extremely [|
extremely Ci
extremely [|
extrenely Cy
extremely [}
extremely [}

extremely 3

[

extremely | |
extremely [_ |
extremely | |
extremely | |
extremely | |
extremely LC]

extremely L

extremely I]

extremely
''APPENDIX EV (cont.)

21. Blue _s« Not: at all [_] a little [| quite a bit | extremely C]
22. Tense Not at all [_] a little | quite a bit LI} extremely CT
23. _Impatient Not at all [] a little CL} quite a bit C_| extremely CT
24. Troubled Not at all [-] a little L] quite a bit Cl extremely C]
25. Sarcastic Not at all [} a little L} quite a bit L| extremely C]
26. Satisfied Not at all[_| a little[ |] quite a bit [| extremely C]
27, _Lively Not at all[] a little[] quite a bit [| extremely [ ]
28. At eases Not at all[] a little[] quite a bit [| — extremely [_]
29. Suspicious Not at all [| a little L] quite a bit C} extremely C]
30. _ Confused Not at all [] a little a} quite a bit CI extremely Cl
3k. Unhappy Not rt all [J a little LC] quite a bit CI extremely C]

32. Check "extremely" Not at all Cl a little L} quite a bit Cl extremely [

 

33. Headache ss Not at all[/] a little[] quite abit {| extremely [|
34, Lonely Not at al1f[-| adlittie[ | quite a bit [| extremely [7]
35. Worn out Not at all{ | a little[/| quite a bit [| extremely [|
36. Sleepy Not at allf| a little[] quite a bit [| extremely [|
37. Weary not at all[-] alittle ["| quite a bit [| extremely ["]
38. Full of pep ‘Not at all[-] a little[ |] quite a bit[ | extremely [_]
39. _Goodnatured Not at all[=| a little[ | quite abit [| extremely [_]
40. _Considerate Not at all[_] alittle[ | quite abit[ | extremely |_|
41. _Angry Not at all[-| alittle[| quite a bit [| extremely [_]
42. Clearly chins Not at all[_] alittle [| quite a bit [| extremely [|

43. Stomach upset Not at all 4 a little C| quite a bit Cl extremely Cl

Y

44. Annoyed Not at all I a little [-} quite a bit Cl extremely a

129
''45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.

60.

Downhearted
Kind
Forgetful
Happy
Friendly
Jittery

On edge
Irritable

Hungry

Trouble Seeing

Rude

Worthless

Tired

Active

Troubled by

conscience

Depressed

Not

Not

Not

Not

Not

Not

Not

Not

Not

Not

Noc

Not

Not

Not

Not

Not

at

at

at

at

at

at

at

at

at

at

at

at

at

at

at

at

APPENDIX

all[[ a
all[] a
all[] a
all[] a
all[| a
all[] a
allf[| a
all[] a
all[|] a
all[] a
all{] a
allf[] a
allf[] a
all[] a
allf] a
allf{] a

130

{V (cont.)

little [-]
little [_]
little ["]
little |]
little | |
little | ]
little | |
little [ |
little [|
little CJ
little []
little [|
little [1
little [|
little [|
little |_|

quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite
quite

quite

a

a

a

bit [1
pit [-]
pit [_]
pit [|
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''TET

Dr. Stewart...

Offices « «: se 6 sx

782-9207

257-6690

SUBJECTIVE RESPONSES

Subject #

Date

 

TIME

Immediate

1/2 hour

1 hour 2hours 3 hours

4 hours

5 hours

1/2 hr post

 

HEADACHE

 

NAUSEA

 

DIZZINESS

 

ABD, PAIN

 

CHEST PAIN

 

EYE, NOSE
THROAT
IRRITATION

 

OTHER

 

 

ODOR:
MILD
MODERATE
STRONG

 

 

 

 

 

 

 

 

 

 

ONLY ABNORMALITIES RECORDED

A XIGN&ddV
''APPENDIX VI
Date: Assessor:

Se

Time:

STAFF ASSESSMENT OF THE SUBJECTS'
MOOD AND BEHAVIOR IN THE CHAMBER

Directions: On the following dimensions assess the subjects' mood and
behavior as observed in interactions with fellow subjects and staff. In
the "comments" section describe the behavior of a particular subject if
it differs appreciably from the behavior of the group in general. Mark
your rating on dash (-), not on a colon (:).

(They are in touch with ALERT tviticinisicines-s-s:-:-:"OUT OF IT" (kind of in a zombie
what is happening around them.) +5 0 -5 state physically but not
mentally here)
CONFUSED/DISORIENTED :-:—:-:-:-:-:-:-:-:-:-: ABLE TO THINK CLEARLY / CONCENTRATE
(Aware of their environment but -5 0 +5 (without extreme effort)
not able to cope with it)
HAPPY 2-:-:-:-:-:-:-:-:-:-:-: DEPRESSED
+5 0 -5
ANXIOUS :-:-:-:-:-:-:-:-:-:-:-: AT EASE
-5 0 +5
FRIENDLY :-:-:-:-:-:-:-:-:-:-:-: HOSTILE
+5 0 -5
UPTIGHT :-:-:-:-:-:-:-:-:-:-:-: CAREFREE
“5 0 +5
FULL OF PEP :-:-:-:-:-:-:-:-:-:-:-: SLEEPY
+5 0 -5
SERIOUS :-:-:-:-:-:-:-:-:-:-:-: GIDDY
-5 0 +5
TALKATIVE :-:-:-:-:-:-:-:-:-:-:-: QUIET
+5 -5
INACTIVE :-:-:-i-:-:-:-:-:-:-:-: ACTIVE
-5 0 +5
COOPERATIVE :-:-:-:-:-:-:-:-:-:-:-: UNCOOPERATIVE
+5 0 =-5
STAGGERING :-:-:-:-:-:-:-:-:-:-:-: IN BALANCE
-5 0 +5

COMMENTS :

132
''APPENDIX VII
PERC/DRU STUDY

BOG SUBIECTS 1-1, 1-2
es GIIREE

ggg SUBIECTS Vis1y 11-2

 

 

 

 

30 eae 8:30

8335 Se-caesade 8:35 ENTER CHAMBER

8:40 8:40 See

8:45 8:45

8:50 <omMich e-h 8:50 = EEG]
Bs55 8255

9:00 9:00.
9:05 7“éxercise w/EKG 9:05 <Ich e-h
9:10 9:10

NLS EUS

9:20 9:20 2 exercise w/EKG
9:25 9325

9:30 9:30

9:35 ze cocktails” 9:35

9:40 9:40

9:45 9:45

9:50 9:50 2 "cotktails'™ a
9255 9:55

10:00 19:00

10:05 10:05

10:10 10:10

10:15 —-bl & br 10:15

10:20, 10:20

10:25 =e"mich e-h & pursuit 10:25

10

230 10:30 “ik &
. > roan YX
10335 10:35 ee
10:40 <= n00 coor 10:40

4<"mich e-h & pursuit

10:45 ———— LO?45
10:50 x=-saccade 10:50 bk
10:55 & 10:55 += hoo coor

 

 

 

11:00 dual task 11:00 fe
11:05 11:05 -
11:10 11:10
Leis : W315
11:20 11:20
11:25 11:32:25
11:30 11:30
1:35 11:35
11:40 11:40
11:45 11:45
11:50 11:50
11:55 11:55
12:00 12:00
72:05 * 12:05
E2210 12:30
12215 7 a aa
12:20 L 12320 L
£2325 U b2225 U
12:30 N 12330 N
12:35 Cc 12:35 G
12:40 EKG H 12:40 EKG | H
12:45 12Qt45: = =
12:50 12350
12:55 12255
1:00 1:00
+ R & ht + wo EEG in PM
1:55 EKG RY? he

:05 EKG

2:
2:00 «~ EXIT CHAMBER 2:10 <— EXIT CHAMBER

133
''APPENDIX VII (CONT.)

PERC/DRUG STUDY

 

 

 

 

yar SUBJECTS  b-! -
mie | SUE, Leda, Tk EEG SUBIECTS T1-3,° bled
8:30 8:30
8:35 8:35
8:40 8:40
8:45 ENTER CHAMBER S845
Ree “ReEht —
: aif ENTER CUAMBER
9:00 =-gaecaae = a Rent
9:05 9:05
9:10 9:10
9:15 ———-——_ 9315 =
EEG
9:20 eo mien en 9:20
9:25 9:25
9:30 ’ 9:30
9:35 ccexercise w/ERG~ 9:35 Soomich é-h
9:40 9:40
9:45 9:45 7
9:50 9:50 =U exercise W/EKG
9355 9355
10:00 10:00
10:05 ~2~eocktails 10:05
10:10 10:10
10:15 10:15
10:20 10:20 S—megcktalis™
10:25 10:25
10:30 10:30
10:35 10:35
10:40 10:40
10:45 -bl & br 10:45
10:50 ~~ 10:50
10:55 somite e=l-s_pursuir 10:55
11:00 11:00
11:05 11:05 ama we
11:10 ~mood-& coord 11:10 &

mich e-h & pursuit

Piet5 f T1215
31320 = Biceada 11220
11225 & 11:25 == nood & coord

11:30 gual task 11:30 [
11:35 11:35

 

 

11:40 11:40
11:45 fe 11:45
1.330 SS 11:50
21:55 11:55
12:00 12:00
12:05 12305
12: 10 12:10
22 eee 12215 -—
12:20 L 12:20 L
12:25 U 12325 U
12:30 N 12:30 N
12:35 é 12°35 C
12:40 EKG H 12:40 EKG H

45 ——_—_—_____— : Vo
12:45 V2845
12:50 12:50
12:55 E2555
1:00 1:00
-_ R & ht \ ““ two EEG in PM
2:15 EKG R & ht
2:20 <-EXIT CHAMBER 2:25 EKG

2:30 <— EXIT CHAMBER

134
''APPENDIX VII (CONT. )

OG SUBJECT T-5, 1-6
230
7.35
240

245

:05 ENTER CHAMBER
:10 a as

. ing ceca
:25 —~saccade

250 +4 ch e=

10:05 22 exercise W/EKG

 

Ibe 15 _--bl & br

11:20 ,
11:25 <2—ieh =f & pursuit

11:40 =

11:45 |
11250 wz

11:55 &
12:00 dual task

12:40 EKG

-
nN
w
wa
mazar

 

R & ht
2°35 EKG
2:40 <€— EXIT CHAMBER

PERC/DRUC STUDY

EEG SUBJECTS 11-5, TI-6

:30
:3B
2:40
245
750
£55
9:00
205
210
s15
20

wovovowowvuvuwvvuvvuvwuypvVuemanannmnnwnona

 

122.35
11:40
11:45
11:50
11:55
12:00
12:05
12:10
12:15
12:20
12:25
12230
42:35
12:40
12:45
12250
12255

1:00

+

2245

135

ENTER CHAMBER
een

 

*<mnich e-h

«+ exercise w/ EKG

+ cocktails

 

-bl & br

+“<_ mich e-h & pursuit

«<< moo coor

EKG

~

 

two EEG in PM

R & ht
EKG
''APPENDIX VIII NO NAME

SUMMARY in Script) PERC/DRUG STUDY

DEBRIEFING QUESTLONNAIRE

Prepared by S. Marlow, M.S.

Were you able to determine whether or not you were receiving alcohol
in your juice?

never sometimes often! always &
Do you believe that you received one dose, two different doses or

more than two different doses of alcohol over the course of the
entire study?

one_j two_7 more than two_ |

Did you answer question #2 on the basis of the way the drinks tasted,
by the effects they had, or by both?

taste 9 effects |] both 6

 

On the days you were given medication, were you able to determine
whether or not you were receiving Valium rather than a drug free pill?

never] sometimes 6 often _2 always

Before the study began you were told that you would be given two
different doses of Valium. Were you able to determine on which days
you were receiving the 6mg. dose and on which days you were receiving
the 10mg. dose of Valium?

never 4 sometimes 4 often] always

When under the influence of Valium, did you try to do your best on:

the Michigan--

never sometimes often 5 always 4
the pursuit tracking--

never sometimes] often 3 always 5
the Flanagan--

never sometimes] often 5 always 3
the dual task--

never sometimes  ] often 4 always 4

When under the influence of alcohol, did you try to do your best on:

the Michigan--

never sometimes] often 3 always 5
the pursuit tracking--

never sometimes] often 3 always 5§

*ALL nine subjects completed the questionnaire.

136
''APPENDIX VIII (cont,)

the Flanagan--
never sometimes often 5 always 4

 

the dual task--
never __ sometimes ]. often 3 always §

 

7. Did Sandi fail to see errors (skipping a hole) that you made on the
Michigan?

never gs sometimes |] often always

 

8. Did you take the mood test seriously and try to answer it honestly?

never sometimes often 2 always 7

 

9. With "1" indicating most, "2" the next greatest, and "3" the least,
please rank the following to show in your opinion the degree to which
#2 ap, 5 fected your responses on the mood test:
of

Response

1 6 things happening in my life that had nothing to do with the
2 3 chamber run...
3 0
1 7 the chemicals (perc vapors, Valium, alcohol) I was exposed to
2 3 during the study...
3 4

tT ?_ social interactions (or the lack of them) taking place in the
2 3 chamber...
3 6

10. Did the requirement of putting a pseudonym on your mood test keep
you from being honest?

never 6 sometimes 2 often_] always

 

11. If you had it to do over again would you prefer to put your real
name, a pseudonym, or no name on the mood test?

real name _ 2 pseudonym _3 no name_ 4

12. Did you have an idea of what you were scoring on the Michigan by any
means other than sheer intuition?

never 7 sometimes 1 often 1 always

 

13. Did you have an idea of what you were scoring on the pursuit tracking
by any means other than intuition and the feedback the machine gave
you (the clicks)?

 

never sometimes 4 often 4 always 1

14. Do you feel that when Rick tested you on the pursuit you performed
differently than when Tom tested you?

never 2 sometimes 3 often_1 always 3

 

137
''15.

16.

17.

18.

19.

20.

APPENDIX VIII (cont,)

Do you feel that when Dr. Hake tested you on the Flanagan you performed
differently than when Bert tested you?

never 5 sometimes 2 often 2 always

 

To what extent did the noise (conversation, laughing, joking) on the
alcohol days influence your performance on the:

Michigan--

not at all a little bit 3 quite a bit 2 extremely 1
pursuit tracking--

not at all_/ a little bit 4 quite a bit 2 extremely 2

Flanagan--

not at all _/ a little bit 3 quite a bit 4 extremely I
mood test—-

not at all 4 a little bit / quite a bit 43 extremely 1

If so, in what way for each of the above?

5Ss Stated that the noise affected their ability to concentrate.
384 Stated that their own Laughter made performance difficult.

How frequently did lack of sleep influence your performance negatively?

never ° sometimes 4 often always

 

To what extent did the boredom of the day to day routine, schedule,
affect your performance negatively on the behavioral tests?

not at all_ 4 a little bit 95 quite a bit extremely

Did you fall asleep during the dual task between the tones (your
signal to type)?

never § sometimes 2 often! always

 

On the dual task, did you make typing errors (e.g. typing four numbers,
two numbers, or hitting the wrong key) while typing in the number of
times you saw the white light blink?

never? sometimes 7 often always

 

138
''APPENDIX VIII (cont. )

If so, explain what type of error.

48s stated that they hit the wrong numbers.
38s stated that they entered mone or Less than thiee digits.

Rotary purs. 5; Mich. coord. 2;

21. Which test did you find most difficult? d. 1

22. Which test did you find most challenging? Rotary purs. 8; Mich. coord. 1

Flanagan coord. 5; Mich. coord. 1;
23. Which test did you find most boring? pyap tasks 1; EFG 1

24. How do you feel about behaviorally-oriented medical research after
your experience at the Department of Environmental Medicine?

not worthwhile has some value_g no opinion_g worthwhile _j

very worthwhile 7

25. Did you feel exploited by any of the procedures or tests you were
subjected to?

never _g sometimes often _7] always

If so, what tests or procedures made you feel this way?

The S who responded "often" stated, "treatment and attitude of some
of the professionals".

Additional Comments:

"Not enough chairs or cubicles"

"It was a very pleasant experience working with both the peopke in
the group and the Dept. stag”.

139
''APPENDIX VIII (cont.)

NO NAME

DEBRIEFING QUESTIONNAIRE (cont.)

Try to answer the following four questions as objectively and honestly as
possible:

Ls

Were you accurate in de*ermining when you were receiving alcohol?

not at all a little bit! quite a bit I extremely 7

Were you accurate in detecting on which days you were receiving the
low dose of alcohol and on which days you were receiving doses twice
as strong?

not at all_ 4 a little bit 2 quite a bit / extremely 2

Were you accurate in determining when you were receiving Valium?

not at all_ 3 a little bit / quite a bit 4 extremely ]

Were you accurate in detecting on which days you were receiving the
6mg. dose of Valium <.ad on which days the 10mg. dose?

not at all 7 _a little bit 1 quite a bit extremely 1

140
''ADDENDUM*
DUAL-ATTENTION TASK ANALYSIS

PCE-Alcohol Combination

Response times for the dual-attention task (see page 8 of the methodology
section), hereafter referred to as the peripheral light test, are shown in
Figure 1 of the addendum for the different PCE-alcohol treatment combinations.
Each of the nine data points in the figure represents the mean response time

of five subjects for both conditions of peripheral light detection: peripheral-
lights alone and peripheral-lights plus central counting. In the latter
condition, only response times for those trials were included where the

central count was correct or within plus or minus one value of the correct

count. Inspectionof Figure 1 indicates that PCE had little influence on

600

590

T

(msec)

900

‘TIME

25 ppm D apa

450-
100 ppm

RESPONSE

400-

 

ree

| | _|
0.0 0.75 1.50

ALCOHOL (ML/kg )

Figure 1. The effects of the three concentrations of PCE with
three different levels of administered alcohol on
response time of five subjects averaged over both
conditions of the peripheral-light task.

 

*Prepared by Vernon R. Putz, Research Psychologist, Behavioral and Motivational
Factors Branch, DBBS, NIOSH, Cincinnati, Ohio.

141
''ADDENDUM (cont,)

response times for peripheral lights, while alcohol, as 100-proof vodka, at the
low dose of 0.75 ml/kg appeared to increase response time, only to be reduced
at the higher alcohol level of 1.50 ml/kg. This observation was confirmed in
the analysis of variance. No significant interactions occurred among the
levels of PCE and the alcohol conditions (F (4, 16) = 0.31, p >0.01). However,
a significant main effect was found with alcohol F (2, 8) = 9.65, p <0.01. The
Newman-Keuls range test indicated that the control mean of 442 msec (no
alcohol) was significantly different from the intermediate alcohol level, which
produced a mean response time of 488 msec, p < 0.1. No further significant
differences were found between the control and the high alcohol level or
between the intermediate and high levels.

A main methodological interest with the peripheral light test was to determine
if information loading of the subject by adding a second task of counting a
central light blinking would serve to aid in the differentation of treatment
effects by reducing the subject's short term compensatory capability. Analysis
of variance revealed the dual-task condition was significantly different from
the single activity of peripheral-light detection (F 1, 4) = 45.7, p <0.01l).
Mean response time for the dual-task condition was 490 msec as compared to

435 msec for the single-task condition. However, no significant differences
were found in the three way interaction involving PCE, alcohol and the task
conditions (F (4, 16) = 1.47, p >0.01). In other words, the dual-task condition
increased general response time, but did not differentially affect the nine
treatment combinations.

The above analyses were performed on the mean response times for all 30
peripheral light locations. In the subsequent analysis,the data were grouped
according to the position of the peripheral lights, or angle of presentation,
namely, far left, far right,and center. Center lights were those defined to
be within + 10° of the straight ahead position, while the far left and far
right included the range of 30 - 70° to the left or right of center. Mean
response times across all conditions averaged 429 msec for the lights
positioned on the far left, 448 msec for those on the far right, and 417 msec
for the lights within + 10° center. Although the orientation of the peripheral
lights did produce a significant main effect across all task and treatment
conditions (F (2, 8) = 13.29, p <0.01), this variable did not interact with
the PCE and alcohol treatment combinations (F (8, 32) = 0.82 p >0.01). Due
in part to the high visibility of the peripheral lights, and the task
procedure, misses and false positives were very infrequent, and accounted for
less than 2% of the total trial data which resulted in too few responses to
warrant subsequent analysis. Blink-counting during the dual-task condition
was also very accurate and did not reflect any treatment effects.

PCE-Diazepam Combination

The data for the PCE-diazepam treatments averaged across the two task
conditions for three subjects are shown in Figure 2 of the addendum. With
zero diazepam or placebo, PCE appeared to increase the response times slightly.
However, analysis of variance indicated that neither PCE nor diazepam were
significant as a main effect and did not interact in any manner (F (6, 12) =
1.37, p >0.01). The only significant variable was task condition (F (1, 2) =
840, p <0.01). Since the task conditions did not significantly interact with
the PCE-diazepam treatment conditions (F (6, 12) = 1.51, p >0.01), the task

142
''ADDENDUM (cont. )

 

 

650+
3 600
E
= “100 ppm
w 550
= 25 ppm
a O ppm
% 500+
oO
a
n
Ww
a
450
to 4
Oo P 6 mg 10mg
CONTROL PLACEBO
DIAZEPAM

Figure 2. The effects of three concentrations of PCE at
each of the four conditions of diazepam adminis-
tration on response timé of three subjects averaged
over both conditions of the peripheral-light task.

variable did not aid in differentiating the treatment combinations or have
any particular meaning in the present context.

The effect of the angle of presentation of the peripheral lights was also
analyzed for the PCE-diazepam conditions. The orientation of the lights did

significantly influence response times (F (2, 4) = 29.5, p <0.01). Lights
located to the far left of center produced a mean response time of 492 msec,
to the far right 514 msec, and 461 msec were recorded for lights in the
center of the subject's visual field (+10°). Both left and right values were
significantly different from the center.

A significant three-way interaction occurred with diazepam, lamp orientation,
and task condition (F (6, 12) = 3.6, p <0.05). Figure 3 of the addendum

shows the relationships. Three things are apparent on inspection of the
figure: (a) the dual-task condition resulted in generally higher response
times, (b) response times to the peripheral lights were slower than the
central, and (3) no trend with regard to diazepam was evident. The expectation
that the effects of the PCE and drug treatments on response time would be

143
''Figure 3.

ADDENDUM (cont. )

   

 

 

 

990r
FR-D
930F
FL-D
%
ao Ol0r
E
FR-S
Ww
s 490-
ri c-D
wi 470 = KEY
z FR-D = FAR RIGHT-DUAL TASK
oO FL-D = FAR LEFT-DUAL TASK
a FR-S = FAR RIGHT-SINGLE
” C-D =CENTER -OUAL
WwW 450+ FL-S FL-S =FAR LEFT- SINGLE
a C-S =CENTER - SINGLE
c-s
430-
0
CONTROL PLACEBO

DIAZEPAM

A three-way interaction among the four conditions of
diazepam administration, the two conditions of the
peripheral-light task: single and dual, and the three
angles of light presentation: far right, far left, and
center is indicated. Peripheral-light response times
were measured to an accuracy of + 1 msec.

144
''ADDENDUM (cont, )

more evident by the added stress of responding to peripheral lights while
simultaneously counting a central blinking light received no support in this
study with three subjects. Variations in the data with regard to misses,
false positives, and central light blinking accuracy were extremely small
and did not warrant analysis.

The general conclusion from this behavioral test was that the peripheral-

light test,as applied, provided little insight into possible PCE-diazepam and
PCE-alcohol interactions. Furthermore, the test did not reveal any significant
or consistent trend with regard to the main effects of PCE, alcohol, or diazepam.

I 4 5 ve U.S. GOVERNMENT PRINTING OFFICE: 1977—757-057/6710
'' 

 

——_—

7.

 

 

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