540-1-86-005
Office of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
vvEPA
HEALTH EFFECTS ASSESSMENT
FOR 1,1,1-TRICHLOROETHANE
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EPA/540/1-86-005
September 1984
HEALTH EFFECTS ASSESSMENT
FOR 1.1,1-TRICHLOROETHANE
U.S. Environmental Protection Agency
Office of Research and Development
Office of Health and Environmental Assessment
Environmental Criteria and Assessment Office
Cincinnati, OH 45268
U.S. Environmental Protection Agency
Office of Emergency and Remedial Response
Office of Solid Waste and Emergency Response
Washington, DC 20460
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DISCLAIMER
This report has been funded wholly or In part by the United States
Environmental Protection Agency under Contract No. 68-03-3112 to Syracuse
Research Corporation. It has been subject to the Agency's peer and adminis-
trative review, and H has been approved for publication as an EPA document.
Mention of trade names or commercial products does not constitute endorse-
ment or recommendation for use.
11
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PREFACE
This report summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with
1,1,l-Tr1chloroethane. All estimates of acceptable Intakes and carcinogenic
potency presented 1n this document should be considered as preliminary and
reflect limited resources allocated to this project. Pertinent toxlcologlc
and environmental data were located through on-Hne literature searches of
the Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/CATALOG data
bases. The basic literature searched supporting this document 1s current up
to September, 1984. Secondary sources of Information have also been relied
upon 1n the preparation of this report and represent large-scale health
assessment efforts that entail extensive peer and Agency review. The
following Office of Health and Environmental Assessment (OHEA) sources have
been extensively utilized:
U.S. EPA. 1980a. Ambient Water Quality Criteria for Chlorinated
Ethanes. Environmental Criteria and Assessment Office, Cincinnati,
OH. EPA 440/5-80-029. NTIS PB 81-117400.
U.S. EPA, 1982. Revision and update of hazard profile on 1,1,1-
trlchloroethane. Prepared by the Environmental Criteria and
Assessment Office, Cincinnati, OH, OHEA for the Office of Solid
Waste and Emergency Response, Washington, DC.
U.S. EPA. 1984. Health Assessment Document for 1,1,1-TMchloro-
ethane (Methyl Chloroform). EPA-600/8-82-003F. NTIS PB84-183565.
The intent 1n these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited in
scope tending to generate conservative (I.e., protective) estimates. Never-
theless, the interim values presented reflect the relative degree of hazard
associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for sys-
temic toxicants (toxicants for which cancer is not the endpolnt of concern).
The first, the AIS or acceptable intake subchronic, is an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval (I.e., for an Interval that
does not constitute a significant portion of the lifespan). This type of
exposure estimate has not been extensively used or rigorously defined, as
previous risk assessment efforts have been primarily directed towards
exposures from toxicants in ambient air or water where lifetime exposure 1s
assumed. Animal data used for AIS estimates generally Include exposures
with durations of 30-90 days. Subchronic human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
111
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The AIC, acceptable Intake chronic, Is similar In concept to the ADI
(acceptable dally Intake). It 1s an estimate of an exposure level that
would not be expected to cause adverse effects when exposure occurs for a
significant portion of the llfespan [see U.S. EPA (1980b) for a discussion
of this concept]. The AIC 1s route specific and estimates acceptable
exposure for a given route with the Implicit assumption that exposure by
other routes 1s Insignificant.
Composite scores (CSs) for noncardnogens have also been calculated
where data permitted. These values are used for ranking reportable quanti-
ties; the methodology for their development Is explained in U.S. EPA (1983a).
For compounds for which there is sufficient evidence of carc1nogen1dty,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980b). Since cancer Is a
process that 1s not characterized by a threshold, any exposure contributes
an Increment of risk. Consequently, derivation of AIS and AIC values would
be Inappropriate. For carcinogens, q-|*s have been computed based on oral
and inhalation data if available.
1v
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ABSTRACT
In order to place the risk assessment evaluation 1n proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate Inter-
pretation and use of the quantitative estimates presented.
Several subchronlc Inhalation studies In a number of species have been
conducted. An Inhalation AIS of 756 mg/day was estimated based on a 90-day
continuous Inhalation exposure study 1n guinea pigs. This estimate may
require revision when more complete human data are available.
Only one chronic Inhalation study has been conducted (Quast et al.,
1978). In this study, rats were exposed to 4765 mg/m3 6 hours/day, 5
days/week. The AIC estimated from this study 1s 442 mg/day. This estimate
may also require revision when more complete data are available. A CS of 2
was also calculated from this study based on mild hepatocellular lesions
observed at 9549 mg/m3.
Only one oral bloassay was located (NCI, 1977), 1n which rats In all
exposure groups exhibited poor survival as a result of murlne pneumonia.
1,1,1-Trlchloroethane treated animals appeared to be more severely affected
than controls. The low dose 750 mg/kg was used to estimate an AIC of 37.5
mg/day by applying an uncertainty factor of 1000. This Is the same approach
taken 1n the development of an ambient water quality criterion for this
compound (U.S. EPA, 1980a).
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and Helen Ball was >,the Project
Officer. The final documents In this series were prepared for the Office of
Emergency and Remedial Response, Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by:
Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1. ENVIRONMENTAL CHEMISTRY AND FATE
2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1.
2.2.
ORAL
INHALATION
3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1.
3.2.
3.3.
3.4.
SUBCHRONIC
3.1.1. Oral
3.1.2. Inhalation
CHRONIC
3.2.1. Oral
3.2.2. Inhalation
TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.3.1. Oral
3.3.2. Inhalation
TOXICANT INTERACTIONS
4. CARCINOGENICITY
4.1.
4.2.
4.3.
4.4.
5. REGUL
HUMAN DATA
4.1.1. Oral
4.1.2. Inhalation
BIOASSAYS
4.2.1. Oral
4.2.2. Inhalation
OTHER RELEVANT DATA
WEIGHT OF EVIDENCE
ATORY STANDARDS AND CRITERIA
Page
1
1
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, , 1
1
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1
1
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1
1
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1
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1
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1
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TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT 10
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 10
6.1.1. Oral 10
6.1.2. Inhalation 10
6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 10
6.2.1. Oral 10
6.2.2. Inhalation 10
6.3. CARCINOGENIC POTENCY (q-,*) 10
6.3.1. Oral 10
6.3.2. Inhalation 10
7. REFERENCES 10
APPENDIX: Summary Table for 1,1 ,l-Tr1chloroethane 10
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable Intake chronic
AIS Acceptable Intake subchronlc
BSP Sulfobromophthaleln
BUN Blood urea nitrogen
bw Body weight
CAS Chemical Abstract Service
CNS Central nervous system
CS Composite score
LOAEL Lowest-observed-adverse-effect level
MED Minimum effective dose
NOEL No-observed-effect level
ppm Parts per million
RV(j Dose-rating value
RVe Effect-rating value
SGOT Serum glutamlc oxalacetlc transamlnase
STEL Short-term exposure limit
TLV Threshold limit value
TWA Time-weighted average
1x
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• 1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
1,1,1-trlchloroethane (CAS No. 71-55-6), also known as methyl chloroform,
are given as follows:
Chemical class: Halogenated aliphatic hydrocarbon
Molecular weight: 133.41
Vapor pressure: 123 mm Hg at 25°C (Mabey et al., 1981)
Water solubility: 1495 mg/i at 25°C (Horvath, 1982)
1334 mg/a, at 25°C (Banerjee et al., 1980)
Octanol/water partition
coefficient: 295 (Banerjee et al., 1980)
B1oconcentrat1on factor: 9 1n whole body of blueglll (Lepomls
macrochlrus) (U.S. EPA, 1980a)
Half-life In air: 2.2-4.8 years (Singh et al., 1981;
Maklde and Rowland, 1981)
Half-life In water: 20-25 minutes (Callahan et al., 1979)
1.5-7 days (estimated)
The estimated half-life of 2.2-4.8 years Indicates that this compound
may transport from troposphere to stratosphere, where it can contribute to
depletion of the ozone layer. The estimated range for the half-life of
1,1,1-trlchloroethane 1n water has been derived from the reaeration rate
ratio of 0.533 (Mabey et al., 1981) and the oxygen reaeration rate range of
0.19-0.96 day'1 (Mabey et al., 1981).
No quantitative soil mobility value expressed as a retardation factor
for 1,1,1-trichloroethane in soil could be located 1n the literature; how-
ever, since this compound 1s less water soluble and has a lower octanol/
water partition coefficient (Mabey et al., 1981) than its isomer I,l,2-tr1-
chloroethane, Us soil retardation factor should be lower than that of
1,1,2-trichloroethane. For 1,1,2-trichloroethane, the soil retardation
-1-
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factor for a soil depth of 140 cm and an organic carbon content of 0.087%
has been estimated to be 1.2 (Wilson et al., 1981).
The half-life of 1,1,l-tr1chloroethane 1n soil could not be located 1n
the literature; however, evaporation Is expected to be the predominant loss
mechanism from the soil surface (Bouwer et al., 1981). In subsurface soil,
blodegradatlon of 1,1,l-tr1chloroethane Is probably a slow process (Tabak et
al., 1981). Therefore, this compound 1s expected to remain significantly
undegraded In subsurface soil and may leach Into groundwater. Bouwer et al.
(1981) studied the Teachability of 1,1 ,l-tr1chloroethane from soil, and Page
(1981) detected the presence of this compound 1n groundwater at high fre-
quency (78%).
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL MAMMALS
2.1. ORAL
The chloroethanes are likely to be absorbed easily following 1ngest1on
or Inhalation (U.S. EPA, 1980a). Stewart (1971) concluded that 1,1,1-trl-
chloroethane 1s "rapidly and completely" absorbed from the gastrointestinal
tract of humans and rapidly and preferentially distributed to the CNS.
Stewart and Andrews (1966) reported the case of acute (non-fatal) Intoxica-
tion resulting from the accidental ingestion of 1 ounce of 1,1,1-trichloro-
ethane. The concentration of the compound measured over a period of time in
expired air was found to be equivalent to that resulting from inhalation
exposure to 500 ppm in air. Absorption from the gastrointestinal tract
appeared to be rapid and complete.
2.2. INHALATION
1,1,1-Trlchloroethane has been investigated for use as an anesthetic
because of Us rapid pulmonary absorption and distribution to the CNS (U.S.
EPA, 1984). It was considered to be a more potent anesthetic than tri-
chloroethylene and somewhat safer than chloroform, which has a similar odor
and physical properties.
The kinetics of the pulmonary uptake of 1,1,1-trlchloroethane have been
studied by a number of investigators (Monster et al.,. 1979; Humbert and
Fernandez, 1977). These studies have been collectively summarized and
interpreted by the U.S. EPA (1984).
Inhaled 1,1,l-tr1chloroethane rapidly equilibrates with alveolar capil-
lary blood. The rate of absorption depends largely on the blood/air parti-
tion coefficient, which has been estimated at 3.3 (Sato and Nakajlma,
1979). Pulmonary absorption, initially rapid, slows markedly until
-3-
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eqlUbMum 1s reached. The percent of 1,1,1-tMchloroethane retained In the
body during any given breath cycle Is described by the formula (C -C )/
CT x 100, where CT 1s the concentration 1n Inspired air and C. 1s the
II A
concentration 1n alveolar air. Initially, a larger percentage of the con-
centration 1n Inspired air 1s retained than when equilibrium has been
reached. Monster et al. (1979) and Humbert and Fernandez (1977) exposed
volunteers to 1,1 ,l-tr1chloroethane at 70 or 140 ppm for 4 and 8 hours. At
equilibrium, which was reached 1n 4 hours, retention was estimated by
Monster et al. (1979) to be 30% of the Inhaled dose, but 40% less than that
by Humbert and Fernandez (1977). These data were sufficient for the U.S.
EPA (1984) to classify 1,1 ,l-tr1chloroethane as a poorly absorbed partially
soluble vapor.
Although no toxlcoklnetlc data could be found 1n the available litera-
ture concerning absorption after either oral or Inhalation exposure, Stahl
et al. (1969) reported levels of 60, 62 and 120 ppm, respectively, 1n the
blood of three victims of fatal Intoxication (Ingested or Inhaled), Indicat-
ing rapid absorption by either route. Other quantitative data regarding the
absorption of 1,1 ,l-tr1chloroethane could not be located 1n the available
literature.
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Pertinent data regarding the subchronlc oral exposure of
man or experimental animals to 1,1,1-trlchloroethane could not be located In
the available literature.
3.1.2. Inhalation. Adams et al. (1950) exposed animals to various con-
centrations (5000 ppm: guinea pigs, rats, rabbits; 3000 ppm: guinea pigs,
rats, monkeys; 1500 ppm: guinea pigs; 650 ppm: guinea pigs) of I,l,l-tr1-
chloroethane for 7 hours/day, 5 days/week for -1-3 months. Body weights,
relative organ weights and BUN were recorded, and hlstopathologlcal examina-
tions were performed on selected major organs. Guinea pigs had slight but
significantly reduced growth rate at all exposure levels. BUN remained nor-
mal In all test groups. Slight fatty liver degeneration was observed 1n the
3000 ppm group, which had progressed to "slight to moderate" In the 5000 ppm
group. Additionally, testlcular degeneration of varying degrees was
observed 1n the males of the 5000 ppm group.
Torkelson et al. (1958) subjected rats, rabbits, guinea pigs and monkeys
to 500, 1000, 2000 or 10,000 ppm 1,1 ,l-tr1chloroethane 1n the air to estab-
lish safe conditions for repeated exposure. Animals were exposed to 500 ppm
for 7 hours/day, 5 days/week for 6 months. From these preliminary studies,
H was determined that the female guinea pig was the most sensitive species
of those tested. Parameters of toxlclty evaluated were growth rate, general
appearance, mortality, hematology, organ weights and gross and microscopic
pathology. Rats, guinea pigs, rabbits and monkeys appeared to be unaffected
after exposure for 6 months. Female guinea pigs tolerated exposure to 1000
ppm for 0.6 hours/day, 5 days/week, with no observed effects and male rats
tolerated 10,000 ppm for 0.5 hours/day, 5 days/week, presumably for 6
-5-
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months, with no evidence of organ pathology. This study defined a NOEL of
500 ppm 1n rats, guinea pigs, rabbits and monkeys.
U.S. EPA (1982) discussed the study by Prendergast et al. (1967) that
apparently defined a NOEL of 370 ppm 1n a variety of species. Groups of 15
Long-Evans or Sprague-Dawley rats, 15 Hartley guinea pigs, 3 squirrel mon-
keys, 3 New Zealand rabbits and 2 beagle dogs were exposed continuously to
1,1,1-trlchloroethane for 90 days at either 135 or 370 ppm.
McNutt et al. (1975) exposed CF-1 mice to 1,1,1-trlchloroethane concen-
trations of 5400 mg/m3 and 1350 mg/m3 continuously for up to 14 weeks.
In the high-dose animals, cytoplasmlc alterations were observed 1n the cen-
trllobular hepatocytes upon electron microscopic evaluation. Necrosis of
hepatocytes occurred 1n 40% of the high-dose group after 12 weeks of expo-
sure. Moderate Hver trlglycerlde accumulation was evident 1n this group.
Tr1glycer1de accumulation peaked following 7 weeks of exposure and declined
during subsequent weeks. "M1ld to minimal" cytoplasmlc alterations were
seen 1n the low-dose group. Necrosis and fat accumulation were not ob-
served. Rats, dogs and monkeys were exposed to the same concentrations, but
exposure-related effects were not demonstrated 1n these species.
Stewart et al. (1975) exposed 20 human subjects to 500 ppm 1,1,1-trl-
chloroethane for 7.5 hours/day, 5 days/week for 3 weeks. No effects on
clinical blood or urine chemistries or on measurements of pulmonary function
were noted. The subjects did, however, complain of fatigue, Irritation and
headache.
3.2. CHRONIC
3.2.1. Oral. Pertinent data regarding chronic oral exposure of man to
1,1,1-trlchloroethane could not be located 1n the available literature. The
only report of chronic oral exposure of laboratory animals was the NCI
(1977) carc1nogen1dty bloassay conducted with Osborne-Mendel rats.
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Originally, doses of 3000 or 1500 mg/kg bw dissolved. 1n corn oil were
given by gavage 5 days/week to groups of 50 rats of each sex. Marked signs
of Intoxication 1n all treatment groups caused termination of the experiment
after a few weeks. The experiment was restarted with new rats at dosages of
1500 or 750 mg/kg, 5 days/week for 78 weeks. During the second year, yellow
discoloration of the fur of the lower abdomen, Increased ocular and nasal
discharge and dyspnea were noted. Typical signs of aging were noted 1n all
groups of rats Including controls, but seemed more severe In 1,1,1-trl-
chloroethane-exposed rats. Survival data presented In Table 3-1 Indicate a
negative association with treatment which was significant (p<0.04) 1n
treated male rats.
The NCI (1977) blbassay also Included B6C3F, mice. Groups of 50 mice
of each sex were administered 2000 or 4000 mg 1,1,1-trlchloroethane In corn
oil/kg bw by gavage 5 days/week for 78 weeks. Because no signs of toxldty
were observed, the dosages were raised to 2500 and 5000 mg/kg after 10
weeks, and again to 3000 and 6000 mg/kg after another 10 weeks In -the
low- and high-dose groups, respectively. Resultant TWA doses, expanded to
reflect treatment of 5 days/week, were 2005 and 4011 mg/kg/day In low- and
high-dose groups, respectively. Untreated controls consisted of 20 mice of
each sex; no vehicle control animals were used 1n these studies. A reduc-
tion of body weight gain, which appeared to be related directly to treat-
ment, was observed 1n mice of both sexes. Survival data are presented 1n
Table 3-2. For female mice, a significant (p=0.02) association between
mortality and treatment level was noted. No specific lesions appeared to
account for reduced survival.
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TABLE 3-1
Comparison of Survival of Control Groups with
1,1,l-Tr1chloroethane-Treated Rats3
Dose Group
Male:
Control
Low-dose
High-dose
F ema 1 e :
Control
Low-dose
High-dose
Initial No.
of Animals
20
50
50
20
50
50
No. Alive at
78 Weeks
7
1
4
14
9
12
No. Alive at
110 Weeksb
0
0
0
3
2
1
aSource: NCI, 1977
bT1me at last weighing
-8-
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TABLE 3-2
Comparison of Survival of Control Groups with Survival
of 1,1,l-Tr1chloroethane-Treated Mice*
Dose Group
Male:
Control
Low-dose
High-dose
Female
Control
Low-dose
High-dose
Initial No.
of Animals
20
50
50
20
50
50
No. Alive at
78 Weeks
6
21
14
12
28
14
No. Alive at
90 Weeks
2
15
11
11
23
13
'Source: NCI, 1977
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3.2.2. Inhalation. Acute exposure of humans to 1,1,1-tMchloroethane
resulted 1n disruption of CNS function as manifested by changes 1n reaction
time, perceptual speed, manual dexterity and equilibrium following exposure
to 350 ppm for 3 hours (U.S. EPA, 1980a). Inhalation of 450 ppm for 8 hours
caused eye, nose and throat Irritation, and Impaired perceptive capabilities
under stress conditions (U.S. EPA, 1980a).
Kramer et al. (1976) evaluated the cardiovascular and hepatic functions
of employees exposed to an 8-hour TWA of 4-217 ppm for periods of ~6 years.
Although the U.S. EPA (1980a) did not discuss what clinical parameters were
measured, no statistically significant findings were reported regarding
1,1,1-tMchloroethane. WeHbrecht (1965) reported Irritation In nine women
exposed to a "workroom concentration" of 10 ppm 1,1 ,l-tr1chloroethane. These
women worked over open vats of 1,1,l-tr1chloroethane and occasionally had
their hands Immersed 1n 1t for varying lengths of time. FukaboM et al.
(1976, 1977) determined that significant amounts of 1,1 ,l-tr1chloroethane can
be absorbed through unbroken skin. Furthermore, 1t 1s suspected that air
concentrations of such a volatile liquid directly above open vats were con-
siderably greater than the levels found 1n workroom air. It 1s, therefore,
Impossible to relate the effects reported by this small sample to a specific
level of exposure to 1,1,1-tMchloroethane.
Sek1 et al. (1975) reported on 196 male workers exposed to I,l,l-tr1-
chloroethane for >5 years at concentrations of 4, 25, 28 or 53 ppm. Routine
clinical pathological blood and urine chemistries failed to reveal evidence
of hepatic or renal malfunction. On the basis of these tests, the ability of
workers to detect tuning fork vibrations and evaluation of answers from a
questlonalre, Seke et al. (1975) concluded that exposure to <53 ppm
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1,1,1-trlchloroethane resulted 1n no dose-related effects. There were no
control subjects 1n this study and H was unclear how frequently the concen-
tration data were obtained. It was suspected (U.S. EPA, 1980a) that actual
concentrations experienced by these workers were 1n excess of those reported.
Maronl et al. (1977) studied a cohort of 21 women exposed for 6.5 years
to an average concentration of 1,1,l-tr1chloroethane of 110-345 ppm. An
evaluation of neurophyslologlcal function (specific tests not reported) re-
vealed no neurotoxldty 1n exposed workers compared with seven unexposed con-
trol subjects (U.S. EPA, 1980a).
Only one report of chronic animal exposure to 1,1,l-tr1chloroethane by
Inhalation was found 1n the available literature. Quast et al. (1978)
exposed 96 rats of each sex to 875 or 1750 ppm 1,1,1-trlchloroethane for 6
hours/day, 5 days/week for 12 months, followed by an observation period of 19
months. Animals were monitored for decreased life span and changes 1n hema-
tology, clinical chemistry, and gross and microscopic pathology. The only
effect reported was focal hepatocellular change 1n high-dose females. The
lower dose level of 875 ppm appeared to represent a NOEL 1n this study. This
concentration, expanded to continuous exposure, assuming an Inhalation rate
of 0.26 mVday and a body weight of 0.35 kg for rats, corresponds to a
dosage of 633 mg/kg/day.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. No reports of teratogenldty of 1,1,1-trlchloroethane caused
by oral exposure 1n humans, and no studies of teratogenldty of orally-admin-
istered 1,1 ,l-tr1chloroethane 1n animals could be located 1n the available
literature.
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3.3.2. Inhalation. Pertinent data regarding the teratogenlclty or feto-
toxlclty of 1,1,l-tr1chloroethane 1n humans could not be located In the
available literature. Results of animal experiments In mice and rats were
negative. Swetz et al. (1975) exposed Swiss-Webster mice to 875 ppm
1,1,1-trlchloroethane for 7 hours/day on days 6-15 of gestation; day 0 was
the day a vaginal plug was first observed. Control mice were maintained on
filtered air. On day 18, fetuses were collected by Caesarean section. All
fetuses were examined for external anomalies; half of the fetuses were
examined for soft tissue malformations by free-hand sectioning, and half were
cleared, stained and examined for skeletal malformations. From each Utter,
one fetus was subjected to complete hlstopathologlcal examination. Exposure
to 875 ppm 1,1,1-trlchloroethane for 7 hours/day on days 6-15 of gestation
was associated with slightly but not significantly reduced maternal body
weights, but was not associated with fetoxlclty or teratogenlclty.
Schwetz et al. (1975) exposed pregnant rats on gestation days 6-15 to 875
ppm 1,1,1-trlchloroethane using the same protocol that had been used with
mice. Rats were terminated on gestatlonal day 21; fetuses were collected by
Caesarean section and were examined for external malformation. From each
Utter, 50% of the fetuses were examined for soft tissue malformation, and
the other 50?4 were examined for skeletal malformation. A randomly selected
fetus from each litter was serially sectioned for complete hlstologlcal
evaluation. There was no evidence of maternal or fetal toxldty or terto-
genlclty 1n any of the 23 Utters examined.
3.4. TOXICANT INTERACTIONS
Tralger and Plaa (1974) examined the effects of pretreatment with ace-
tone or Isopropanol on the hepatotoxlclty of selected chlorinated ethanes In
mice as evaluated by SGOT activity. Pretreatment with acetone or Isopro-
panol did not alter the toxlclty of 1,1,1-trlchloroethane 1n mice.
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Pretreatment of mice for 3 days with 5 g ethanol/kg by gavage and admini-
stration of 2.75 ml 1,1,1-trlchloroethane by IntraperHoneal Injection on
the 4th day resulted In depressed liver function as evidenced by BSP reten-
tion. BSP was elevated from 0.91 mg/100 mi serum In nonpretreated mice to
3.76 mg/100 ma serum 1n ethanol-pretreated mice (Klaassen and Plaa, 1966).
Cornish and Adefuln (1966) demonstrated that pretreatment of rats with
ethanol enhanced the hepatotoxldty of 1,1,1-trlchloroethane as evaluated by
SGOT activity. Pretreatment with phenobarbHal did not affect the hepato-
toxldty of 1,1,1-trlchloroethane as evaluated by SGOT levels (Cornish et
al., 1973). No further details concerning these studies were available from
U.S. EPA (1980a).
Exposure of rats to 3000 ppm 1,1,1-trlchloroethane In the air for 24
hours decreased sleeping time Induced by IntraperHoneal Injection of hexo-
barbltal, meprobamate or zoxazolamlne 24 hours post-exposure. Inhibitors of
protein synthesis blocked the effect of 1,1,1-trlchloroethane on hexobarbl-
tal Induced sleeping time (Fuller et al., 1970). The hypothesis that hepatic
mlcrosomal enzymes were Induced by the chlorinated hydrocarbon was supported
by data showing In. vitro stimulation of mlcrosomal aniline hydroxylase
activity by 1,1,1-trlchloroethane (Van Dyke and Rlkans, 1970). Potent1at1on
of toxlclty was not observed 1n extensive studies with a 3:1 mixture of
1,1,1-trlchloroethane and tetrachloroethylene (by weight) In mice, rats,
guinea pigs, rabbits, dogs and human subjects (Rowe et al., 1963).
-13-
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• 4. CARCINOGENICITY
4.1. HUMAN DATA
No reports of cancer In humans associated with 1,1,1-trlchloroethane
could be located 1n the available literature.
4.2. BIOASSAYS
4.2.1. Oral. The NCI (1977) sponsored a bloassay of the carclnogenlclty
of 1,1.1-tMchloroethane 1n Osborne-Mendel rats and 86C3F1 mice (see Sec-
tion 3.2.1). Low survival of both male and female treated rats may have
precluded significant development of tumors late 1n life. A variety of neo-
plasms were observed 1n both treated and matched control rats. These neo-
plasms were common to aged rats and were not significantly related to
dosage. Malignancies found only In treated rats Included papillary cysta-
denocardnoma In the subcutls (1/50 high-dose females), urinary bladder
transitional cell carcinoma (1/50 high-dose males), malignant glloma In the
brain (1/48 low-dose males) and mesenteMc metastatlc osteosarcoma (1/50
high-dose females)-.
Similarly, mice suffered early heavy mortality that was significantly
related to dosage level for females. A variety of neoplasms was observed in
both treated and matched control mice. Although not statistically signifi-
cant, malignant lymphoma was a relatively common finding In both treated and
control mice. Other pathologic lesions found were those common to aging
mice and were not significantly related to treatment. Malignancies found
only In treated mice were flbrosarcoma (1/42 low-dose females) and sarcoma
(1/50 high-dose females) 1n the skin, hepatocellular adenoma (3/49 high-dose
males), hepatocellular carcinoma (1/49 high-dose males) and hemanglosarcoma
(1/47 low-dose males).
-14-
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NCI (1977) concluded that "these studies cannot be regarded as appropri-
ate tests for the cardnogenlcity of [1,1 Jtrlchloroethane] In the test ani-
mals because of the abbreviated Hfespans of both the rats and the mice."
4.2.2. Inhalation. A brief report of the Investigation of 1,1,1-trl-
chloroethane-lnduced cardnogenlcity by Inhalation was located 1n the liter-
ature. Quast et al. (1978) exposed 96 rats of both sexes to 875 or 1750 ppm
1,1,1-trlchloroethane for 6 hours/day, 5 days/week for 12 months, followed
by an additional 19-month observation period. As discussed In Section
3.2.2., the only effect reported was a focal hepatocellular change 1n high-
dose females. No significant dose-related neoplasms were reported.
4.3. OTHER RELEVANT DATA
Few reports of mutagenldty of 1,1,1-trlchloroethane were located 1n the
available literature. Positive results 1n Salmonella typhlmurlum strain
TA100 were observed by several Investigators (Simmon et al., 1977; F1shbe1n,
1979; Snow-et al., 1979). Exogenous metabolic activation was not required
to obtain a positive result, but did Increase the number of revertants/
plate. Henschler et al. (1977) and Taylor (1978) obtained negative results
with S. typhlmurlum strain TA100. j>. typhlmurlum strain TA1535 was positive
with metabolic activation (Farber, 1977) and without activation (Nestmann et
al., 1980). Negative results were obtained In an experiment 1n which pre-
cautions were not taken to prevent evaporation of the compound (Simmon et
al., 1977). Negative results were obtained with J>. typhlmurlum strains
TA98, TA1537 and TA1538 (Farber, 1977; Simmon et al., 1977; Taylor, 1978;
Nestmann et al., 1980). It was suggested that volatilization was respons-
ible for the negative results 1n these tests (U.S. EPA, 1984).
-15-
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1,1,1-TMchloroethane was not mutagenlc 1n the gene conversion or
mltotlc recombination tests with Saccharomyces cerevlslae (Farber, 1977;
Simmon et al., 1977) or the host-mediated forward mutation assay using
Schlzosaccharomyces porobe 1n mice. The chemical also failed to produce
chromosomal aberrations In the bone marrow cells of rats (Rampy et al.,
1977), but responded positively In the mammalian cell transformation test
with rat embryo cells (Price et al., 1978).
4.4. WEIGHT OF EVIDENCE
IARC has not evaluated the risk to humans associated with oral or
Inhalation exposure to 1,1,1-trlchloroethane. Applying the criteria for
evaluating the overall weight of evidence of cardnogenldty to humans
proposed by the Carcinogen Assessment Group of the U.S. EPA (Federal
Register, 1984), 1,1,l-tr1chloroethane 1s most appropriately designated a
Group D - Not Classified chemical.
-16-
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5. REGULATORY STANDARDS AND CRITERIA
The ACGIH (1980) recommended a TLV of 350 ppm and an STEL of 450 ppm to
protect against anesthetic effects and objections to odor, based primarily
on the study by Kramer et al. (1978). Other countries, however, recommended
much lower levels, as summarized 1n Table 5-1.
The Code of Federal Regulations (1981) standard for an 8-hour TWA expo-
sure to 1,1,1-trlchloroethane Is 350 ppm 1n workplace air. According to
U.S. EPA (1980a), NIOSH recommended a 10-hour TWA exposure criterion of 200
ppm to protect against CNS responses and cardiovascular and respiratory
effects.
Based on extrapolations of data from the NCI (1977) bloassay, the U.S.
EPA (1980a) set the ambient water quality criteria at 18.4 mg/a.
When used as a solvent In pesticide formulations or as a post-harvest
fumlgant for citrus fruit, 1,1,1-tMchloroethane 1s exempt from requirement
of a tolerance for residues (IARC, 1979).
-17-
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TABLE 5-1
Current Regulatory Standards and Criteria for 1,1,l-Tr1chloroethane
Standard or Criteria
Recommendation
Reference
TLV, U.S.
STEL, U.S.
TLV, E. Germany (1973)
TLV, W. Germany (1974)
TLV, Sweden (1978)
TLV, USSR (1972)
TLV, Czechoslovakia (1969)
Ambient water quality
criteria
NIOSH (current)
NIOSH^( proposed)
350 ppm (-1900 mg/m3)
450 ppm (-2450 mg/m3)
90 ppm
200 ppm
70 ppm
4 ppm
90 ppm
18.4 mg/2.
350 ppm
200 ppm
ACGIH, 1980
ACGIH, 1980
ACGIH, 1980
ACGIH, 1980
ACGIH, 1980
ACGIH, 1980
U.S. I-PA, 1980a
IARC, 1979
U.S. EPA, 1980a
-18-
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
6.1.1. Oral. Since no pertinent data concerning subchronlc oral exposure
to 1,1,1-trlchloroethane could be found In the available literature, no cal-
culation of an AIS 1s possible.
6.1.2. Inhalation. The Adams et al. (1950) study (see Section 3.1.2.)
defined a LOAEL 1n guinea pigs of 650 ppm 1,1,1-trlchloroethane 7 hours/day,
5 days/week, associated with slight retardation of growth. Assuming an
Inhalation rate of 0.23 mVday and a body weight of 0.43 kg, this corres-
ponds to a dosage of 395 mg/kg/day. The significance of the reported retar-
dation of growth Is questionable, however, because similar effects were not
observed by Prendergast et al. (1967) 1n a study 1n which guinea pigs were
exposed continuously to 370 ppm for 90 days. Applying the same assumptions
mentioned above, this exposure corresponds to 1080 mg/kg/day.
Torkelson et al. (1958) defined a NOEL of 500 ppm In guinea pigs exposed
to 1,1,1-trlchloroethane for 7 hours/day, 5 days/week for 6 months. Using
the same assumptions for Inhalation rate and body weight of guinea pigs,
this level corresponds to a dosage of 304 mg/kg/day. In this study guinea
pigs were more sensitive than the other species tested.
The lowest exposure concentration which defined an effect level was the
14-week continuous exposure study conducted by HcNutt et al. (1975) using
mice. In this study, the lowest dose tested, 1350 mg/m3, produced elec-
tron microscopically detectable cytoplasmlc alterations 1n hepatocytes fol-
lowing continuous exposure and Is appropriately designated a LOAEL.
Since the goal^f the risk estimates In this document Is to project
acceptable exposure concentrations for continuous exposure situations, and
since extrapolation from Intermittent exposure regimens to projected contln
-19-
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uous exposure conditions Is subject to significant uncertainty, use of data
generated using a continuous exposure protocol Is preferable. Two continu-
ous exposure, subchronlc studies have been conducted. HcNutt et al. (1975)
established a LOAEL In mice exposed continuously for 14 weeks to 1350
mg/m3 for electron microscopically detectable alterations In hepatocytes.
The projected dose to the mice 1s 2250 mg/kg/day. The other continuous
exposure protocol (Prendergast et al., 1967) established a NOEL for guinea
pigs exposed to 2014 mg/m3 for 90 days. The projected animal dose 1s 1080
mg/kg/day. An AIS can be calculated from the guinea pig NOEL by multiplying
by 70 kg and dividing by an uncertainty factor of 100 (10 for Interspedes
extrapolation and 10 for 1nter1nd1v1dual variability). The resulting AIS 1s
756 mg/day.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
6.2.1. Oral. The only report of chronic oral exposure to 1,1,1-trl-
chloroethane 1s the NCI (1977) bloassay. Survival time In rats was reduced
significantly 1n both dose groups. The low dose (750 mg/kg) 1s selected for
derivation of an AIC. An uncertainty factor of 10 1s used for Interspecles
extrapolation, a factor of 10 Is used to afford greater protection to un-
usually sensitive paaMlations and a final factor of 10 to extrapolate from a
LOAEL to a NOEL. The general poor health of these rats was attributed pri-
marily to chronic murlne pneumonia, a common syndrome encountered In aging
laboratory rodents. It Is entirely possible that exposure to 1,1,1-trl-
chloroethane may have accelerated this disease process, or that the disease
process may have masked subtle manifestations of 1,1,l-tr1chloroethane-1n-
duced toxlcity. From these data, an AIC 1s calculated as follows:
AIC = 750 mg/kg/dose x 70 kg/man x 5 days/7 days/week * 1000
AIC =37.5 mg/day
-20-
-------
The term, 5 days/7 days/week, 1s applied to adjust for treatment on 5
days/week.
6.2.2. Inhalation. The sole chronic Inhalation evaluation (Quast et al.,
1978) reported a NOEL of 4765 mg/m3 for rats exposed 6 hours/day, 5 days/
week. Assuming an Inhalation rate of 0.26 m3/day and an average body
weight of 0.35 kg for rats, this NOEL results 1n an animal dose of 632
mg/kg/day. A human AIC 1s calculated by multiplying the animal dose by
70 kg, the assumed average body weight of humans, and by applying an uncer-
tainty factor of 100 (10 for Interspedes extrapolation and 10 to afford
greater protection to unusually sensitive Individuals). The resulting AIC
1s 442 nig/day for an average 70 kg human.
U.S. EPA (1983b) computed a CS for the hepatocellular hlstopathology
observed by Quast *afcal. (1978) 1n rats exposed to 1750 ppm (9549 mg/m3)
1,1,1-trlchloroethane for 6 hours/day, 5 days/week for 1 year. A human MED
was calculated by expanding this concentration to continuous exposure and.
assuming that an average human Inhales 20 m3 of air/day and that absorp-
tion of the chemical Is 50%. A human MED of 17,053 results, corresponding
to an RV. of 1. The minor hlstologlcal hepatocellular changes observed
are assigned an RV of 2. A CS of 2 1s calculated by multiplying RVd x
RV .
e
6.3. CARCINOGENIC POTENCY (q^)
Neither the NCI (1977) bloassay nor the study by Quast et al. (1978)
demonstrated evidence for carclnogenlclty of 1,1,1-trlchloroethane by oral
or Inhalation routes, respectively. It Is not possible, therefore, to
derive a q * for 1,1,1-trlchloroethane for either the oral or Inhalation
exposure routes.
-21-
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7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1980.
Documentation of the Threshold Limit Values for Substances 1n Workroom Air,
4th ed., Cincinnati, OH. p. 269-270. (Cited In U.S. EPA, 1982)
Adams, E.M., et al. 1950. Vapor toxldty of 1,1,1-tMchloroethane (methyl
chloroform) dete&ained by experiments on laboratory animals. Arch. Ind.
Hyg. Occup. Med. 1: 225.
Banerjee, S., S.H. Yalkowsky and S.C. Valvanl. 1980. Water solubility and
octanol/water partition coefficients of organlcs. Limitations of the solu-
bility-partition coefficient correlation. Environ. Sc1. Technol. 14:
1227-1229.
Bouwer, E.J., P.L. McCarty and C. Lance. 1981. Trace organic behavior In
soil columns during rapid Infiltration of secondary wastewater. Water Res.
15: 151-159.
Callahan, M.A., M.W. SUmak, N.W. Gabel, et al. 1979. Water-related en-
vironmental fate of 129 priority pollutants, Vol. II. OWPS, OWWM, U.S. EPA,
Washington, DC. EPA-440/4-79-029-b.
Code of Federal Regulations. 1981. OSHA Safety and Health Standards (29
CFR 910.1000)
-22-
-------
Cornish, H.H. and J. Adefuln. 1966. Ethanol potentlatlon of halogenated
aliphatic solvent toxldty. Am. Ind. Hyg. Assoc. J. 27: 57. (Cited 1n
U.S. EPA, 1980a)
Cornish, H.H., B.P. L1ng and M.L. Barth. 1973. PhenobarbHal and organic
solvent toxldty. Am. Ind. Hyg. Assoc. J. 34: 487-492. (Cited In U.S.
EPA, 1980a)
Farber, H. 1977. Manager of Environmental Affairs, Dow Chemical letter to
James Price, Chief of A1r Quality Data Analysis, Texas A1r Control Board,
Austin, TX. NCI, 1977. (Cited In U.S. EPA, 1984.)
Federal Register. 1984. Environmental Protection Agency. Proposed guide-
lines for carcinogenic risk assessment. 49 FR 46294-46299.
F1shbe1n, L. 1979. Potential halogenated Industrial carcinogenic and muta-
genlc chemicals. II. Halogenated saturated hydrocarbons. Sc1. Total
Environ. 11: 163. (Cited In U.S. EPA, 1980a)
Fukaborl, S., K. Nakaal, J. Yonemoto and 0. Tada. 1976. On the cutaneous
absorption of methyl chloroform. J. Scl. Labour. 53: 67-80. (CHed In
U.S. EPA, 1982)
Fukaborl, S., K. Nakaakl, J. Yonemoto and 0. Tada. 1977. On the cutaneous
absorption of 1,1,1-trlchloroethane. J. Sc1. Labour. 53: 89-95. (CHed In
U.S. EPA, 1982)
-23-
-------
Fuller, G.C., et al. 1970. Induction of hepatic drug metabolism 1n rats by
methylchloroform Inhalation. J. Pharmacol. Ther. 175: 311. (Cited 1n U.S.
EPA, 1980a)
Henschler, D., E. Eder, T. Neudecker and M. Metzler. 1977. Cardnogenlclty
of trlchloroethylene: Fact of artifact? Arch. Toxlcol. 37: 233-236.
(CHed 1n U.S. EPA, 1984.)
Horvath, A.L. 1982. Halogenated hydrocarbons. Solubility mlsclblHty with
water. Marcel Dekker, Inc., New York. p. 500.
Humbert, B.E. and J.G. Fernandez. 1977. Exposure to 1,1,1-trlchloroethane:
Contribution to the study of absorption, excretion and metabolism 1n human
subjects. Arch. Mai. Prof. 38: 415-425. (Cited 1n U.S. EPA, 1984.)
IARC (International Agency for Research on Cancer). 1979. 1,1,1-TMchloro-
ethane. in: Some Halogenated Hydrocarbons. IARC Monographs on the Carcino-
genic Risk of Chemicals to Humans. WHO, IARC, Lyon, France. 20: 515-531.
Klaassen, C.D. and G.L. Plaa. 1966. Relative effects of various chlorin-
ated hydrocarbons on liver and kidney function 1n mice. Toxlcol. Appl.
Pharmacol. 9: 139. (Cited In U.S. EPA, 1980a)
Kramer, C.G., et al. 1976. Health of workers exposed to 1,1,1-trlchloro-
ethane -- A matched pair study. Dow Chemical Co., Midland, MI. (CHed 1n
U.S. EPA, 1980a)
-24-
-------
Kramer, C.6., M.G. Ott, J.E. Fulkerson, N. Hicks and H.R. Imbus. 1978.
Health of workers exposed to 1,1,1-tMchloroethane: A matched-pair study.
Arch. Environ. Health. 33: 331-342. (Cited 1n U.S. EPA, 1982)
Mabey, W.R., J.H. Smith, R.T. Podoll, et al. 1981. Aquatic fate process
data for organic priority pollutants. Monlt. Data Sup. D1v., OWRS, Washing-
ton, DC. EPA 440/4-81-014.
Maklde, Y. and F.S. Rowland. 1981. TropospheMc concentrations of methyl
chloroform, CH.Cl-, 1n January 1978 and estimates of the atmospheric
residence times of halocarbons. Proc. NAS. 78: 5933-5937.
Maronl, M., C. Bulgheronl, M.G. CassHto, F. Merluzzl, R. G1l1ol1 and V.
Foa. 1977. A clinical, neurophyslologlcal and behavioral study of female
workers exposed to 1,1 ,T-tr1chloroethane. Scand. J. Work Envlronm. Health.
3: 16-22. (Cited In U.S. EPA, 1982)
McNutt, N.S., R.L. Amster, E.E. McConnell and F. Morris. 1975. Hepatic
lesions 1n mice after continuous Inhalation exposure to 1,1,l-tr1chloro-
ethane. Lab. Invest. 32: 642-654.
Monster, A.C., G. Boersma and H. Steenweg. 1979. Kinetics of I,l,l-tr1-
chloroethane 1n volunteers, Influence of exposure concentrations and work
load. Int. Arch. Occup. Environ. Health. 42: 293-301. (Cited 1n U.S. EPA,
1984.)
-25-
-------
NCI (National Cancer Institute). 1977. Bloassay of 1,1,1-trlchloroethane
for possible carc1nogen1c1ty. Cardnog. Tech. Rep. Ser. No. 3, NCI-CG-TR-3.
p. 70. (Cited 1n U.S. EPA, 1982)
Nestman, E.R., E.G-H. Lee, T.I. Matula, G.R. Douglas and J.C. Mueller.
1980. Mutagenlclty of constituents Identified 1n pulp and paper mill efflu-
ents using the Salmonella/mammal1an-m1crosome assay. Mutat. Res. 79:203-212.
Page, G.W. 1981. Comparison of groundwater and surface water for patterns
and levels of contamination by toxic substances. Environ. Sc1. Technol.
15: 1475-1481.
Prendexgast, J.A., R.A. Jones, L.J. Jenkins, Jr. and J. Selgel. 1967.
Effects on experimental animals of long-term Inhalation of trlchloroethy-
lene, carbon tetrachlorlde, 1,1,l-tr1chloroethane, dlchlorodlfluoromethane
and I,l-d1chloroethylene. Toxlcol. Appl. Pharmacol. 10: 270-289.
Price, P.J., C.M. Hassett and J.I. Mansfield. 1978. Transforming activi-
ties of trlchloroethylene and proposed Industrial alternatives. In. vitro.
14: 290-293. (Cited 1n U.S. EPA, 1984)
Quast, J.F., B.K.J. Leong, L.W. Rampy and P.J. GehMng. 1978. Tox1colog1c
and carcinogenic evaluation of a methylchloroform (1,1,1-trlchloroethane)
formulation by chronic Inhalation In rats — Interim report after 24 months.
Dow Chemical Co., Midland, MI. p. 14. (Cited In U.S. EPA, 1982)
-26-
-------
Rampy, L.W., J.F. Quast, B.K.J. Leong and P.J. GehMng. 1977. Results of
long-term Inhalation toxldty studies on rats of 1,1 ,l-tr1chloroethane and
perchloroethylene formulations. In: Proc. Int. Cong. Toxlcol. Toronto,
p. 27. (Cited 1n U.S. EPA, 1984)
Rowe, V.K., et al. 1963. Toxldty of a solvent mixture of 1,1 ,l-tr1chloro-
ethane and tetrachloroethylene as determined by experiments on laboratory
animals and human subjects. Am. Ind. Hyg. Assoc. J. 24: 541. (Cited In
U.S. EPA, 1980a)
Sato, A. and T. Nakajlma. 1979. A structure-activity relationship of some
chlorinated hydrocarbons. Arch. Environ. Health. 34: 69-75. (Cited 1n
U.S. EPA, 1984)
Schwetz, B.A., B.K.J. Leong and P.J. Gehrlng. 1975. The effect of matern-
ally Inhaled trlchloroethyl-ene, perchloroethylene, methylchloroform, and
methylene chloride on embryonal and fetal development 1n mice and rats.
Toxlcol. Appl. Pharmacol. 32: 84-96. (Cited 1n U.S. EPA, 1984)
Sek1, Y., Y. Urashlma, H. Alkawa, et al. 1975. Trlchloro-compounds In the
urine of humans exposed to methyl chloroform at sub-threshold levels. Int.
Arch. Arbeltsmed. 34: 39-49. (Cited In U.S. EPA, 1982)
Simmon, V.F., et al. 1977. Mutagenlc activity of chemicals Identified In
drinking water. In: Progress In Genetic Toxicology, D. Scott et al., Ed.
Elsevler/North Holland B1omed1cal Press, Amsterdam. (Cited In U.S. EPA,
1980a)
-27-
-------
Singh, H.B., L.J. Salas, A.J. Smith and H. Sh1ge1sh1. 1981. Measurements
of some potentially hazardous organic chemicals In urban environments.
Atmos. Environ. 15: 601-612.
Snow, L.P., B.C. Nalr and B.C. Castro. 1979. Mutagenlc testing of
1,1,1-trlchloroethane In Salmonella strains TA100 and TA98. Northrop Ser-
vices, Inc., Research Triangle Park, NC. (Cited In U.S. EPA, 1984)
Stahl, C.J., et al. 1969. Trlchloroethane poisoning: Observations on the
pathology and toxicology In six fatal cases. J. Forensic Scl. 14: 393.
(Cited 1n U.S. EPA, 1982)
Stewart, R.D. 1971. Methyl chloroform Intoxication: Diagnosis and treat-
ment. J. Am. Med. Assoc. 1789-1792. (Cited 1n U.S. EPA, 1984)
Stewart, R.D. and J.T. Andrews. 1966. Acute Intoxication with methyl
chloroform. J. Am. Med. Assoc. 904-906. (Cited 1n U.S. EPA, 1984)
Stewart, R.D., C.L. Hake, A. Wu, et al. 1975. 1,1,1-Trlchloroethane:
Development of a biologic standard for the Industrial worker by breath anal-
ysis. Medical College of Wisconsin and National Institute of Occupational
Safety and Health. NIOSH-MCOW-ENVM-1,1.l-T-75-4. (Cited 1n U.S. EPA, 1980a)
Tabak, H.H., S.A. Quare, C.J. Mashnl and E.F. Broth. 1981. BlodegradabH-
Hy studies with organic priority pollutant compounds. J. Wales Pollut.
Control. Fed. 53: 1503-1518.
-28-
-------
Taylor, 6. 1978. Personal communication. NIOSH, Morgantown, WV. (Cited
In U.S. EPA, 1984)
Torkelson, T.R. and V.K. Rowe. 1981. Halogenated aliphatic hydrocarbons.
In: Toxicology, Vol. 2B of Patty's Industrial Hygiene and Toxicology, G.D.
Clayton and T.E. Clayton, Ed. 3ohn Wiley and Sons, Inc., New York.
p. 3502-3510.
Torkelson, T.R., F. Oyen, D.D. McCollister and V.K. Rowe. 1958. Toxicity
of 1,1,1-trichloroethane as determined on laboratory animals and human sub-
jects. Am. Ind. Hyg. Assoc. 3. 19: 353-362.
Traiger, 6.J. and G.L. Plaa. 1974. Chlorinated hydrocarbon toxicity.
Arch. Environ. Health. 28: 276. (Cited in U.S. EPA, 1980a)
U.S. EPA. 1980a. Ambient Water Quality Criteria for Chlorinated Ethanes.
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
440/5-80-029. NTIS PB 81-117400.
U.S. EPA. 1980b. Guidelines and Methodology Used in the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water Quality Cri-
teria. Federal Register. 45:79347-79357.
U.S. EPA. 1982. Revision and update of hazard profile on 1,1,1-trichloro-
ethane. Prepared by the Environmental Criteria and Assessment Office, Cin-
cinnati, OH, OHEA for the Office of Solid Waste and Emergency Response,
Washington, DC.
-29-
-------
U.S. EPA. 1983a. Methodology and Guidelines for Reportable Quantity Deter-
minations Based on Chronic Toxldty Data. Prepared by the Environmental
Criteria and Assessment Office, Cincinnati, OH, OHEA for the Office of Solid
Waste and Emergency Response, Washington, DC.
U.S. EPA. 1983b. Reportable Quantity Document for 1,1,1-Trlchloroethane.
Prepared by the Environmental Criteria and Assessment Office, Cincinnati,
OH, OHEA for the Office of Solid Waste and Emergency Response, Washington,
DC.
U.S. EPA. 1984. Health Assessment Document for 1,1,1-Trlchloroethane
(Methyl Chloroform). EPA-600/8-82-003F. NTIS PB 84-183565.
Van Dyke, R.A. and I.E. Rlkans. 1970. Effect of the volatile anesthetics
on aniline hydroxylase and amlnopyrlne demethylase. Blochem. Pharmacol.
19: 1501. (CHed 1n U.S. EPA, 1980a)
Weltbrecht, U. 1965. Tr1 and trl-substltutes 1n the metal Industry.
Zentralb Arbeltsmed. 15: 138-146. (Cited 1n U.S. EPA, 1982)
Wilson, J.T., C.G. Enfleld, W.J. Annlap, R.L. Cosby, D.A. Foster and L.B.
Baskln. 1981. Transport and fate of selected organic pollutants In a sandy
soil. J. Environ. Qua!. 10: 501-506.
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APPENDIX
Summary Table for 1,1,1-Trlchloroethane
Species
Experimental
Dose/Exposure
Effect
Acceptable Intake
(AIS or AIC)
Reference
CO
Inhalation
AIS
AIC
rat
Maximum CS rat
guinea 2014 mg/m3 (continuous)
4765 mg/m3 (6 hours/day,
5 days/week
1750 ppm (9549 mg/m3)
6 hours/day, 5 days/week
for 1 year (RVd = 1)
none
none
756 mg/day
442 mg/day
mild hepatocellular 2
hlstopathologlc
lesions (RVe = 2)
Prendergast
et al., 1971
Quast et al.,
1978
Quast et al.,
1978; U.S.
EPA. 1983b
Oral
AIS
AIC
NA NA
rat 750 mg/kg/day
NA
reduced survival
ND
37.5 mg/day
NA
NCI, 1977
NA = Not applicable; ND = not derived
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