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Hexachloroethane
CASRN 67-72-1
Contents
0167
Hexachloroethane; CASRN 67-72-1
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Hexachloroethane
File On-Line 03/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 04/01/1991
Inhalation RfC Assessment (I.B.) no data 12/01/1992
Carcinogenicity Assessment (II.) on-line 02/01/1994
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Hexachloroethane
CASRN -- 67-72-1
Last Revised -- 04/01/1991
The oral Reference Dose (RfD) is based on the assumption that thresholds exist
for certain toxic effects such as cellular necrosis. It is expressed in units
of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning
perhaps an order of magnitude) of a daily exposure to the human population
(including sensitive subgroups) that is likely to be without an appreciable
risk of deleterious effects during a lifetime. Please refer to the Background
Document for an elaboration of these concepts. RfDs can also be derived for
the noncarcinogenic health effects of substances that are also carcinogens.
Therefore, it is essential to refer to other sources of information concerning
the carcinogenicity of this substance. If the U.S. EPA has evaluated this
substance for potential human carcinogenicity, a summary of that evaluation
will be contained in Section II of this file.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ---------
Atrophy and NOAEL: 1 mg/kg/day 1000 1 1E-3
degeneration of the mg/kg/day
renal tubules LOAEL: 15 mg/kg/day
Rat Subchronic
Dietary Study
Gorzinski et al.,
1985
*Conversion Factors: The doses were estimated by the investigators from body
weights, food consumption and diet analysis data.
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
Gorzinski, S.J., R.J. Nolan, S.B. McCollister, R.J. Kociba and J.L. Mattsson.
1985. Subchronic oral toxicity, tissue distribution and clearance of
hexachloroethane in the rat. Drug Chem. Toxicol. 8(3): 155-169.
Groups of 10 male and 10 female Fischer 344 rats were treated with diets
containing hexachloroethane for 16 weeks. Dosages were 0, 1, 15, or 62
mg/kg/day, as determined by the investigators. The rats were evaluated for
overt signs of toxicity; body weight gain; food consumption; urinalysis,
hematological, and clinical chemistry parameters; organ weights; and gross
pathology. Comprehensive histologic examination was performed on the control
and 62-mg/kg/day groups, while histologic examination of the 1- and 15-
mg/kg/day groups was limited to the liver and kidney. At 15 and 62 mg/kg/day,
male rats had dose-related increased incidences of renal lesions, including
renal atrophy, degeneration, hypertrophy, and dilation. At 62 mg/kg/day,
males had increased absolute and relative kidney weights and peritubular
fibrosis; females had slight renal tubular atrophy and increased liver
weights. No other effects were observed. Thus, 15 mg/kg/day is the LOAEL and
1 mg/kg/day is the NOAEL.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- An uncertainty factor of 1000 was used: 10 to account for interspecies
extrapolation, 10 for the range of sensitivity within the human population to
xenobiotics and 10 for the use of a subchronic study.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
The quality assessment of another chronic gavage bioassay in rats is in
progress (NTP, 1986), but a draft report of results of the preliminary
subchronic gavage study is available (NTP, 1983). In this study, rats were
treated by gavage with 0, 47, 94, 188, 375, or 750 mg/kg/day, 5 days/week for
13 weeks. Body weight gain was reduced at 750 mg/kg/day, behavioral signs of
toxicity were seen at 94 mg/kg/day, and increased relative liver and kidney
weights occurred at 375 mg/kg/day. Dose-related increased incidences of renal
tubular regeneration occurred at 47 mg/kg/day.
In a 6-week inhalation study, rats, dogs, and guinea pigs were exposed to
hexachloroethane 6 hours/day, 5 days/week for 6 weeks at 0, 145, 465, or 2520
mg/cu.m (Weeks et al., 1979). Neurobehavioral effects occurred in rats and
dogs, and reduced body weights, increased relative liver weights, and deaths
occurred in guinea pigs at 2520 mg/cu.m. No effects were observed at 465
mg/cu.m. Based on this inhalation NOAEL in rats, an RfD of 0.03 mg/kg/day
could be calculated using an uncertainty factor of 1000. However, the more
recent 16-week oral study by Gorzinski et al. (1985) is a better basis for the
RfD.
Hexachloroethane has been tested for teratogenicity by oral and inhalation
administration to rats. At gavage doses of 500 mg/kg/day during gestation
there was maternal toxicity, a reduced gestation index, and reduction in the
numbers of fetuses/dam, and increased fetal resorption rates (Weeks et al.,
1979). No effects occurred at 50 or 100 mg/kg/day. Weeks et al. (1979)
administered hexachloroethane to rats by inhalation at 145, 465, or 2520
mg/cu.m, 6 hours/day during gestation. At the two highest doses, maternal
toxicity was observed but there was no evidence of fetoxicity or
teratogenicity.
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Medium
Data Base -- Medium
RfD -- Medium
Medium to high confidence is placed in the Gorzinski et al. (1985) study
because, although it defined a NOAEL and a LOAEL, the study used small groups
of animals. Confidence in the data base is medium because, although
hexachloroethane has been tested for carcinogenicity and teratogenicity, a
NOAEL for chronic toxicity has not been defined. Confidence in the RfD is
therefore medium.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
Other EPA Documentation -- None
Agency Work Group Review -- 12/18/1985, 04/16/1987
Verification Date -- 04/16/1987
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Hexachloroethane
CASRN -- 67-72-1
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Hexachloroethane
CASRN -- 67-72-1
Last Revised -- 02/01/1994
Section II provides information on three aspects of the carcinogenic
assessment for the substance in question; the weight-of-evidence judgment of
the likelihood that the substance is a human carcinogen, and quantitative
estimates of risk from oral exposure and from inhalation exposure. The
quantitative risk estimates are presented in three ways. The slope factor is
the result of application of a low-dose extrapolation procedure and is
presented as the risk per (mg/kg)/day. The unit risk is the quantitative
estimate in terms of either risk per ug/L drinking water or risk per ug/cu.m
air breathed. The third form in which risk is presented is a drinking water
or air concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1
in 1,000,000. The rationale and methods used to develop the carcinogenicity
information in IRIS are described in The Risk Assessment Guidelines of 1986
(EPA/600/8-87/045) and in the IRIS Background Document. IRIS summaries
developed since the publication of EPA's more recent Proposed Guidelines for
Carcinogen Risk Assessment also utilize those Guidelines where indicated
(Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to
Section I of this IRIS file for information on long-term toxic effects other
than carcinogenicity.
__II.A. EVIDENCE FOR CLASSIFICATION AS TO HUMAN CARCINOGENICITY
___II.A.1. WEIGHT-OF-EVIDENCE CLASSIFICATION
Classification -- C; possible human carcinogen
Basis -- Observation of carcinomas in one mouse strain after oral exposure
___II.A.2. HUMAN CARCINOGENICITY DATA
None.
___II.A.3. ANIMAL CARCINOGENICITY DATA
Limited. Technical grade hexachloroethane (98% pure) was administered by
gavage to Osborne-Mendel rats and B6C3F1 mice (50 each male and female) (NCI,
1978). Rats were treated with either 250 or 500 mg hexachloroethane/kg/day, 5
days/week for 23 weeks. After this time animals were rested 1 week and
gavaged for 4 succeeding weeks up to week 78; an observation period of 33-34
weeks followed. Final TWA treatment doses were 212 and 432 mg/kg/day. There
was no evidence of hexachloroethane-induced neoplastic growth in rats. Mice
were administered 500 or 1000 mg/kg/day, 5 days/week, continuously. At week 9
the doses were increased to 600 and 1200 mg/kg/day, and this dosage was
maintained until week 78. Mice were observed for 12-13 weeks after cessation
of treatment. The TWA doses were 590 and 1179 mg/kg/day. Mice of both sexes
showed a significant increase in the incidence of hepatocellular carcinoma.
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
None. Hexachloroethane was not mutagenic for any of 5 Salmonella
typhimurium strains (TA1535, TA1537, TA1538 TA98 or TA100) or for
Saccharomyces cerevisiae D4 in the absence or presence of rat liver
homogenates (Weeks et al., 1979).
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
___II.B.1. SUMMARY OF RISK ESTIMATES
Oral Slope Factor -- 1.4E-2 per (mg/kg)/day
Drinking Water Unit Risk -- 4.0E-7 per (ug/L)
Extrapolation Method -- Linearized multistage procedure, extra risk
Drinking Water Concentrations at Specified Risk Levels:
Risk Level Concentration
-------------------- -------------
E-4 (1 in 10,000) 3E+2 ug/L
E-5 (1 in 100,000) 3E+1 ug/L
E-6 (1 in 1,000,000) 3E+0 ug/L
___II.B.2. DOSE-RESPONSE DATA (CARCINOGENICITY, ORAL EXPOSURE)
Tumor Type -- hepatocelluar carcinomas
Test Animals -- mouse/B6C3F1, male
Route -- gavage
Reference -- NCI, 1978
Administered Human Equivalent Tumor
Dose (mg/kg)/day Dose (mg/kg)/day Incidence
---------------- ---------------- ---------
0 0 3/20
421 27.8 15/50
841 55.5 31/49
___II.B.3. ADDITIONAL COMMENTS (CARCINOGENICITY, ORAL EXPOSURE)
The administered doses are TWA-adjusted for frequency of exposure (5/7
days). Human equivalent doses were adjusted for length of exposure (546
days of a potential lifespan of 637) and weight of the animals (assumed to
be 0.032 kg). The vehicle control group incidence data was used in modeling.
Toxic tubular nephropathy was noted in treated animals of both species.
Rats, but not mice, exhibited dose-related increases in mortality.
The unit risk should not be used if the water concentration exceeds 3E+4
ug/L, since above this concentration the unit risk may not be appropriate.
___II.B.4. DISCUSSION OF CONFIDENCE (CARCINOGENICITY, ORAL EXPOSURE)
Adequate numbers of animals were treated and the tumor response was
dose-related. Background incidence of these tumors is high.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
___II.C.1. SUMMARY OF RISK ESTIMATES
Inhalation Unit Risk -- 4.0E-6 per (ug/cu.m)
Extrapolation Method -- Linearized multistage procedure, extra risk
Air Concentrations at Specified Risk Levels:
Risk Level Concentration
-------------------- ---------------
E-4 (1 in 10,000) 3E+1 ug/cu.m
E-5 (1 in 100,000) 3E+0 ug/cu.m
E-6 (1 in 1,000,000) 3E-1 ug/cu.m
___II.C.2. DOSE-RESPONSE DATA FOR CARCINOGENICITY, INHALATION EXPOSURE
The inhalation risk estimates were calculated from the oral data presented
in II.B.2.
___II.C.3. ADDITIONAL COMMENTS (CARCINOGENICITY, INHALATION EXPOSURE)
The unit risk should not be used if the air concentration exceeds 3000
ug/cu.m, since above this concentration the unit risk may not be appropriate.
___II.C.4. DISCUSSION OF CONFIDENCE (CARCINOGENICITY, INHALATION EXPOSURE)
See II.B.4.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1980
The values in the Ambient Water Quality Criteria Document for Chlorinated
Ethanes received extensive peer and public review.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 07/23/1986
Verification Date -- 07/23/1986
___II.D.3. U.S. EPA CONTACTS (CARCINOGENICITY ASSESSMENT)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_VI. BIBLIOGRAPHY
Substance Name -- Hexachloroethane
CASRN -- 67-72-1
Last Revised -- 04/01/1991
__VI.A. ORAL RfD REFERENCES
Gorzinski, S.J., R.J. Nolan, S.B. McCollester, R.J. Kociba and J.L. Mattsson.
1985. Subchronic oral toxicity, tissue distribution and clearance of
hexachloroethane in the rat. Drug Chem. Toxicol. 8(3): 155-169.
NTP (National Toxicology Program). 1983. Subchronic study with
hexachloroethane in rats. Unpublished report submitted by contract
laboratory. Internal working document.
NTP (National Toxicology Program). 1986. Toxicology and carcinogenesis
studies of hexachloroethane (CAS No. 67-72-1) in F344/N rats (gavage studies).
NTP Tech. Report Ser. No. 361. PB 90-170895/AS.
Weeks, M.H., R.A. Angerhofer, R. Bishop, J. Thomasino and C.R. Pope. 1979.
The toxicity of hexachloroethane in laboratory animals. Am. Ind. Hyg. Assoc.
J. 40: 187-198.
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
NCI (National Cancer Institute). 1978. Bioassay of Hexachloroethane for
Possible Carcinogenicity. CAS No. 67-72-1. NCI-CG-TR-68. Tech. Report Ser.
No. 68. U.S. DHEW. Publ. No. (NIH) 78-1318.
U.S. EPA. 1980. Ambient Water Quality Criteria for Chlorinated Ethanes.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Water
Regulations and Standards, Washington, DC. EPA 440/5-80-029. NTIS PB
81-117400.
_VII. REVISION HISTORY
Substance Name -- Hexachloroethane
CASRN -- 67-72-1
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
09/30/1987 I.A. Oral RfD assessment on-line
03/01/1988 I.A.5. Confidence levels revised
03/01/1988 II.B.3. Text clarified
03/01/1988 II.B.4. Confidence statement revised
03/01/1988 II.C.4. Confidence statement revised
01/01/1991 II. Text edited
01/01/1991 II.C.1. Inhalation slope factor removed (global change)
04/01/1991 I.A. Text edited
04/01/1991 I.A.7. Secondary contact changed
04/01/1991 II. Text edited
04/01/1991 VI. Bibliography on-line
12/01/1991 I.B. Inhalation RfC now under review
12/01/1991 IV.F.1. EPA contact changed
01/01/1992 IV. Regulatory actions updated
12/01/1992 I.B. Work group review date added
02/01/1994 II.D.3. Secondary contact's phone number changed
VIII. SYNONYMS
Substance Name -- Hexachloroethane
CASRN -- 67-72-1
Last Revised -- 03/31/1987
67-72-1
AVLOTHANE
CARBON HEXACHLORIDE
DISTOKAL
DISTOPAN
DISTOPIN
EGITOL
ETHANE HEXACHLORIDE
ETHANE, HEXACHLORO-
ETHYLENE HEXACHLORIDE
FALKITOL
FASCIOLIN
HEXACHLOR-AETHAN
Hexachloroethane
1,1,1,2,2,2-HEXACHLOROETHANE
HEXACHLOROETHYLENE
MOTTENHEXE
NA 9037
NCI-C04604
PERCHLOROETHANE
PHENOHEP
RCRA WASTE NUMBER U131
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0167.HTM
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