EPA-540/1-86-045
Agency
Office of Emergency and
Remedial Response
Washington DC 20460
Office of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
Superfund
HEALTH EFFECTS ASSESSMENT
FOR 1,1,2-TRICHLOROETHANE
Do not
remove
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EPA/540/1-86-045
September 1984
HEALTH EFFECTS ASSESSMENT
FOR 1,1,2-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 1t 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 I,l,2-tr1-
chloroethane. 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/DATALOG 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. 1980b. Ambient Water Quality Criteria for Chlorinated
Ethanes. Environmental Criteria and Assessment Office, Cincinnati,
OH. EPA 440/5-80-029. NTIS PB 81-117400. (Cited In U.S. EPA,
1982)
U.S. EPA. 1982. Hazard Profile on 1,1,2-tr1chloroethane.
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. Review of Toxlcologlc Data 1n Support of Evalua-
tion for Carcinogenic Potential of: 1,1,2-Tr1chloroethane. Pre-
pared by the Carcinogen Assessment Group, OHEA, Washington, DC for
the Office of Solid Waste and Emergency Response, Washington, DC.
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 1s not the endpolnt of concern).
The first, the AIS or acceptable Intake subchronlc, 1s 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 Hfespan). 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 1n ambient air or water where lifetime exposure 1s
assumed. Animal data used for AIS estimates generally Include exposures
with durations of 30-90 days. Subchronlc human data are rarely available.
Reported exposures are usually from chronic occupational exposure situations
or from reports of acute accidental exposure.
Ill
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The AIC, acceptable Intake chronic, 1s similar 1n 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 Hfespan [see U.S. EPA (1980a) 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 1s explained 1n U.S. EPA (1983a).
For compounds for which there 1s sufficient evidence of cardnogenlcHy,
AIS and AIC values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980a). Since cancer 1s a
process that Is 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 1f available.
1v
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ABSTRACT
In order to place the risk assessment evaluation In 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.
No data are available which address the potential cardnogenlcHy of
this compound 1n humans. Limited in vitro mutagenldty evaluations have
been negative. Only one cancer bloassay has been conducted. In this study
1,1,2-tr1chloroethane was carcinogenic In mice, but not rats by oral
administration. Using the mouse data, a human q-|* of 5.73xlO~2
(mg/kg/day)"1 was computed.
No data addressing the potential cardnogenlcHy of this compound by the
Inhalation route were located.
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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 wasithe Project
Officer. The final documents 1n 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.
2.
3.
4.
5.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1.
2.2.
ORAL
INHALATION
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
CARCINOGENICITY
4.1.
4.2.
4.3.
4.4.
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
REGULATORY STANDARDS AND CRITERIA
Page
1
. . . 2
. . . 2
. . . 2
. . . 3
3
. . . 3
3
, . . 3
. . . 3
. . . 3
. . . 3
. . . 3
. . . 3
4
. . . 5
. . . 5
. . . 5
. . . 5
. . . 5
. . . 5
. . . 5
. . . 5
. . . 6
. . . 7
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TABLE OF CONTENTS (cont.)
Page
6. RISK ASSESSMENT . 8
6.K ACCEPTABLE INTAKE SUBCHRONIC (AIS) 8
6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 8
6.3. CARCINOGENIC POTENCY (q-|*) 8
6.3.1. Oral 8
6.3.2. Inhalation 8
7. REFERENCES 10
APPENDIX A: Summary Table for 1,1,2-Tr1chloroethane 13
APPENDIX B: Cancer Data Sheet for Derivation of * 14
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
AIC Acceptable intake chronic
AIS Acceptable Intake subchronlc
BCF B1oconcentrat1on factor
bw Body weight
CAS Chemical Abstract Service
CS Composite score
ppm Parts per million
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
1,1,2-tMchloroethane (CAS No. 79-00-5) are as follows:
Chemical class:
Molecular weight:
Vapor pressure:
Water solubility:
Log octanol/water
partition coefficient:
BCF:
Soil mobility:
(predicted as retardation
factor for a soil depth of
140 cm and organic carbon
content of 0.087%)
Half-lives In
Air:
Water:
halogenated aliphatic hydrocarbon
133.41 (Verschueren, 1983)
30.3 mm Hg at 25°C
(Mackay et al., 1982)
4500 mg/a. at 20°C
(Verschueren, 1983)
2.38 (Konemann, 1981)
21 (estimated from the equation of
VeHh et al., 1979)
<1.5 (WHson et al., 1981)
24 days (Singh et al., 1981)
1.9 days (Zoeteman et al., 1980)
The half-life of 1,1,2-tr1chloroethane In soil could not be located In
the available literature; however, volatilization 1s expected to be the
predominant loss mechanism from the soil surface. In subsurface soil,
blodegradatlon of this compound 1s likely to be a slow process (Wilson et
al., 1981). Based on the aqueous solubility and octanol/water partition
coefficient, 1,1,2-tr1chloroethane 1s expected to leach Into groundwater
(Page, 1981; Wilson et al., 1981).
-1-
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Pertinent data regarding the absorption of orally administered
1,1,2-tMchloroethane could not be located In the available literature. By
analogy to other chlorinated ethanes, 1,1,2-tr1chloroethane 1s rapidly
absorbed from the gastrointestinal tract (U.S. EPA, 1980b).
2.2. INHALATION
Pertinent data regarding the absorption of Inhaled 1,1,2-tr1chloroethane
could not be located In the available literature. By analogy to other
chlorinated ethanes, 1,1,2-tr1chloroethane 1s rapidly absorbed following
Inhalation exposure.
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3. ' TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. Pertinent data regarding the subchronlc oral tox1c1ty of
1,1,2-trlchloroethane could not be located In the available literature.
3.1.2. Inhalation. In an unpublished Dow Chemical Company study,
Torkelson and Rowe (1981) exposed rats, guinea pigs and rabbits (numbers and
strains unspecified) to 15 ppm (81.8 mg/m3} 1,1,2-trlchloroethane for 7
hours/day, 5 days/week for 6 months, or to 30 ppm (163.7 mg/m3) 7 hours/
day, 5 days/week for 16 exposures. No effects were noted on organ weight,
hematology or clinical chemistry, but fatty changes were observed 1n female
rats at the high dose.
3.2. CHRONIC
3.2.1. Oral. The NCI (1978) administered TWA doses of 46 or 92 mg/kg
bw/day to Osborne-Mendel rats and 195 or 390 mg/kg bw/day to B6C3F1 mice (50
anlmals/spedes/sex/dose) by gavage, 5 days/week for 78 weeks, followed by a
13-35 week observation period. The corresponding controls consisted of 20
animals each. No dose-related, non-neoplast1c changes were reported for
either sex of either species.
3.2.2. Inhalation. Pertinent data regarding the chronic Inhalation
toxldty of 1,1,2-trlchloroethane could not be located 1n the available
literature.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1. Oral. Pertinent data regarding the teratogenlclty or other repro-
ductive effects of orally administered 1,1,2-trlchloroethane could not be
located 1n the available literature.
3.3.2. Inhalation. Pertinent data regarding the teratogenlclty or other
reproductive effects of Inhaled 1,1,2-trlchloroethane could not be located
1n the available literature.
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3.4. TOXICANT INTERACTIONS
Tralger and Plaa (1974) reported that pretreatment with acetone or
Isopropyl alcohol (2.5 mg/kg bw by gavage) resulted 1n an Increased hepato-
toxlc response to, and enhanced the effects of threshold doses of 1,1,2-trl-
chloroethane 1n mice.
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4. CARCINOGENICITY
4.1. HUMAN DATA
4.1.1. Oral. Pertinent data regarding the oral cardnogenlcHy of 1,1,2-
tMchloroethane 1n humans could not be located 1n the available literature.
4.1.2. Inhalation. Pertinent data regarding the cardnogenlcHy of
Inhaled 1,1,2-tr1chloroethane 1n humans could not be located 1n the avail-
able literature.
4.2. BIOASSAYS
4.2.1. Oral. The NCI (1978-) treated groups of 50 male and 50 female
B6C3F1 mice or Osborne-Mendel rats with 195 or 390 mg/kg bw/day (mice) or 46
or 92 mg/kg bw/day (rats), 5 days/week for 78 weeks by gavage. The mice
were observed for an additional 13 weeks and the rats for an additional 35
weeks. There was no relationship between 1,1,2-trlchloroethane treatment
and the development of tumors 1n rats. All groups of treated mice had
significantly (p<0.01) Increased Incidences of hepatocellular carcinomas.
The Incidences were 37/49, 18/49, 2/20 and 0/20 (males) and 40/45, 16/48,
0/20 and 2/20 (females) for the high-dose, low-dose, vehicle control and
untreated control groups, respectively. The Incidence of adrenal pheo-
chromocytomas was Increased 1n the high-dose groups (both sexes).
4.2.2. Inhalation. Pertinent data regarding the cardnogenlcHy of
Inhaled 1,1,2-trlchloroethane 1n experimental animals could not be located
In the available literature.
4.3. OTHER RELEVANT DATA
1,1,2-trlchloroethane has been tested for mutagenldty 1n the Ames
Salmonella typh1mur1um assay, both by the standard plate Incorporation assay
and by exposing the cells to vapors of the compound In a closed container
(Barber et a!., 1981; Simmon et al., 1977). Doses up to 158.9 pmol/plate,
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a level toxic to the Salmonella strains used (TA1535, TA100, TA98), produced
only negative results, both with and without the addition of rat liver S-9
preparation to provide metabolic activation.
4.4. WEIGHT OF EVIDENCE
Since 1,1,2-tr1chloroethane has only been demonstrated to Induce liver
tumors 1n one strain of mice 1n one experiment, the evidence for the
carclnogenlclty of 1,1,2-tr1chloroethane 1n animals 1s best considered
"limited". Since no data are available regarding the carclnogenlclty of
1,1,2-tr1chloroethane In humans, the chemical 1s best classified as a Group
C compound - Possible Human Carcinogen, by applying the criteria for weight
of evidence proposed by the Carcinogen Assessment Group of the U.S. EPA
(Federal Register, 1984).
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5. REGULATORY STANDARDS AND CRITERIA
The ACGIH (1980) has established a TLV of 10 ppm (-45 mg/m3} and a
STEL of 20 ppm (-90 mg/m3), based on "the toxlcologlcal resemblance to
symmetric tetrachloroethane and by analogy with the TLV for chloroform."
The Occupational Safety and Health Administration has adopted this TLV as a
general Industry standard (Code of Federal Regulations, 1981).
The U.S. EPA (1980b) has estimated that a concentration of 6.0
1n ambient water will result 1n an excess lifetime cancer risk of 10~5.
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6. RISK ASSESSMENT
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS)
1,1,2-Trlchloroethane 1s a chemical associated with liver tumors 1n mice
and for which data are sufficient for calculation of a q^. It 1s, there-
fore, Inappropriate to calculate an oral or Inhalation AIS for 1,1,2-trl-
chloroethane.
6.2. ACCEPTABLE INTAKE CHRONIC (AIC)
1,1,2-Trlchloroethane 1s a chemical associated with liver tumors 1n mice
and for which data are sufficient for calculation of a q^*. It 1s, there-
fore, Inappropriate to calculate an oral or Inhalation AIC for I,l,2-tr1-
chloroethane.
6.3. CARCINOGENIC POTENCY (q^)
6.3.1. Oral. One study (NCI, 1978) has Indicated that 1,1,2-tr1chloro-
ethane 1s carcinogenic 1n B6C3F1 mice (see Section 4.2.1.}. The U.S. EPA
(1980b) has calculated a human q^ of 5.73xlO~2 (mg/kg bw/day)"1,
based on the Incidence of hepatocellular carcinoma In male mice (Table 6-1)
and using a linearized multistage model.
6.3.2. Inhalation. Pertinent data regarding the cardnogenldty of
1,1,2-tr1chloroethane In humans or experimental animals exposed by Inhala-
tion could not be located 1n the available literature.
A complete data set for the derivation of the q * 1s presented 1n
Appendix B.
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TABLE 6-1
Incidence of Hepatocellular Carcinoma 1n Male B6C3F1 Mice
Exposed to 1,1,2-Trlchloroethane*
Dose
(mg/kg bw/day)
Incidence
(No. Responding/No. Tested)
0
195
390
2/20
18/49
37/49
*Source: U.S. EPA, 1980b
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7. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyg1en1sts). 1980.
Documentation of the Threshold Limit Values for Substances 1n Workroom A1r,
4th ed. Cincinnati, OH. p. 406. (Cited In U.S. EPA, 1982)
Barber, E.D., W.H. Donlsh and K.R. Mueller. 1981. A procedure for the
quantitative measurement of the mutagenlclty of volatile liquids In the Ames
Salmonella/mlcrosome assay. J. Mutat. Res. 90(1): 31-48. (Cited In U.S.
EPA, 1982)
Code of Federal Regulations. 1981. OSHA Safety and Health Standards. 29
CFR 1910.10000.
Federal Register. 198.4. Environmental Protection Agency. Proposed guide-
lines for carcinogenic risk assessment. 49 FR 46294-46299.
Konemann, H. 1981. Quantitative structure-activity relationships In fish
toxldty studies. Part 1: Relationship for 50 Industrial pollutants.
Toxicology. 19: 209-221.
Mackay, 0., A. Babra, D.W. Chan and W.Y. Sh1u. 1982. Vapor pressure corre-
lations for low-volatility environmental chemicals. Environ. Sc1. Technol.
16: 645-649.
NCI (National Cancer Institute). 1978. Bloassay of 1,1,2-tr1chloroethane
for possible cardnogenlcHy. U.S. OWEW Tech. Rep. Ser. 74, Washington, DC.
Publ. No. NIH 78-1324. (Cited In U.S. EPA, 1983b)
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Page, G.W. 1981. Comparison of groundwater and surface water for patterns
and levels of contamination by toxic substances. Environ. Scl. Technol.
15: 1475-1481.
Simmon, V.F., K. Kauhanen and R.G. Tardlff. 1977. Mutagenlc activity of
chemicals Identified 1n drinking water. Toxlcol. Environ. Sd. 2: 249-258.
(CHed 1n U.S. EPA, 1980b, 1982)
Singh, H.B., L.J. Salas, A.J. Smith and H. Shlgelshl. 1981. Measurements
of some potentially hazardous organic chemicals In urban environments.
Atmos. Environ. 15: 601-612.
Torkelson, T.R. and V.K. Rowe. 1981. Halogenated aliphatic hydrocarbons:
1,1,2-tMchloroethane. In: Patty's Industrial Hygiene and Toxicology, 3rd
rev. ed., Vol. 2B. John Wiley and Sons, Inc., New York. p. 3510-3513.
Tralger, G.J. and G.L. Plaa. 1974. Chlorinated hydrocarbon toxldty.
Arch. Environ. Health. 28: 276. (CHed 1n U.S. EPA, 1980b)
U.S. EPA. 1980a. Guidelines and Methodology Used 1n the Preparation of
Health Effects Assessment Chapters of the Consent Decree Water Quality
Criteria. Federal Register. 45: 79347-79357.
U.S. EPA. 1980b. Ambient Water Quality Criteria for Chlorinated Ethanes.
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-
80-029. NTIS PB 81-117400. (Cited 1n U.S. EPA, 1982)
-11-
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U.S. EPA. 1982. Hazard Profile on 1,1,2-tr1chloroethane. 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. 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. Review of Tox1colog1c Data 1n Suport of Evaluation for
Carcinogenic Potential of: 1,1,2-TMchloroethane. Prepared by the Carcino-
gen Assessment Group, OHEA, Washington, DC for the Office of Solid Waste and
Emergency Response, Washington, DC.
Velth, G.D., D.L. DeFoe and B.V. Bergstedt. 1979. Measuring and estimating
the bloconcentratlon factor of chemicals In fish. J. F1sh Res. Board Can.
36: 1040-1048.
Verschueren, K. 1983. Handbook of Environmental Data on Organic Chemistry,
2nd ed. Van Nostrand Relnhold Company, New York. 1310 p.
Wilson, J.T., C.G. Enfleld, W.J. Dunlap, R.L. Cosby, D.A. Foster and L.B.
Baskln. 1981. Transport and fate of selected organic pollutants 1n a sandy
soil. J. Environ. Qua!. 10: 501-506.
Zoeteman, B.C.J., K. Harmsen, J.B.H.J. Llnders, C.F.H. Morra and W. Slooff.
1980. Persistent organic pollutants 1n river water and groundwater of the
Netherlands. Chemosphere. 9: 231-249.
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APPENDIX A
Summary Table for 1,1,2-Trlchloroethane
CO
I
Carcinogenic Species
Potency
Inhalation
Oral mice
Experimental
Dose/Exposure
0, 195 or 390
mg/kg bu/day
Effect
hepatocellular
carcinoma
qi* Reference
NO
5.73xlO"2
(mg/kg/day) *•
NCI,
U.S.
1978;
EPA, 1980
ND = Not derived
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APPENDIX B
Cancer Data Sheet for Derivation of q-|*
Compound: 1,1,2-tr1chloroethane
Reference: NCI, 1978
Species, Strain, Sex: mice, B6C3F1, male
Body weight: 0.33 kg (measured)
Length of exposure (le) = 546 days
Length of experiment (Le} = 637 days
Llfespan of animal (L) = 637 days
Tumor site and type: liver, hepatocellular carcinoma
Route, vehicle: oral, gavage
Experimental Doses
or Exposures
(mg/kg/day)
0
195
390
Transformed Dose*
(mg/kg/day)
0
119.14
239.143
Incidence
No. Responding/No. Tested
or Examined
2/20
18/49
37/49
*Calculated to reflect treatment on 5 days/week and for 546 days of 637-day
experimental period
Unadjusted q-|* from study = 4.4611191xlO~3 (mg/kg/day)"1
Human q-|* = 5.73xlO~3 (mg/kg/day)'1
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