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1,1,2,2-Tetrachloroethane (CASRN 79-34-5)

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0193

1,1,2,2-Tetrachloroethane; CASRN 79-34-5


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 1,1,2,2-Tetrachloroethane

File First On-Line 03/31/1987

Category (section)
Status
Last Revised
Oral RfD Assessment (I.A.) no data
Inhalation RfC Assessment (I.B.) no data
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 — 1,1,2,2-Tetrachloroethane
CASRN — 79-34-5

Not available at this time.

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_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — 1,1,2,2-Tetrachloroethane
CASRN — 79-34-5

Not available at this time.

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_II.  Carcinogenicity Assessment for Lifetime Exposure

Substance Name — 1,1,2,2-Tetrachloroethane
CASRN — 79-34-5
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 Human Carcinogenicity

__II.A.1. Weight-of-Evidence Characterization

Classification — C; possible human carcinogen

Basis — Increased incidence of hepatocellular carcinomas in mice

__II.A.2. Human Carcinogenicity Data

None.

__II.A.3. Animal Carcinogenicity Data

In a bioassay undertaken by NCI (1978) 50 each male and female Osborne- Mendel rats and B6C3F1 mice were gavaged with technical grade (90% pure) 1,1,2,2,-tetrachloroethane in corn oil, 5 days/week. Treatment was over 78 weeks, followed by observation periods of 32 weeks for the rats and 12 weeks for the mice. The high and low average doses (incorporating varying dosage levels throughout the treatment period) were, respectively, 108 and 62 mg/kg/day for male rats, 76 and 43 mg/kg/day for female rats, and 282 and 142 mg/kg/day for mice of both sexes. Control groups consisted of 20 animals/sex and species. Vehicle controls received corn oil at the same rate as the high-dose animals; untreated controls were not intubated. Ten of the high-dose female rats died within the first 5 weeks of the study, but the association between increased dosage and elevated mortality was not statistically significant for male rats. Significantly increased mortality was also evident in the high-dose mice of both sexes. No statistically significant incidence of neoplasms was observed in rats. A highly significant dose-related increase in the incidence of hepatocellular carcinomas was observed in both male and female mice.

__II.A.4. Supporting Data for Carcinogenicity

1,1,2,2-Tetrachloroethane is mutagenic for the Salmonella typhimurium missense mutants TA1530 and TA1535 and selectively inhibits growth of E. coli polA (Rosenkranz 1977; Brem et al., 1974).

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_II.B. Quantitative Estimate of Carcinogenic Risk from Oral Exposure

__II.B.1. Summary of Risk Estimates

Oral Slope Factor — 2.0E-1 per (mg/kg)/day

Drinking Water Unit Risk — 5.8E-6 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)
2E+1 ug/L
E-5 (1 in 100,000)
2E+0 ug/L
E-6 (1 in 1,000,000)
2E-1 ug/L

__II.B.2. Dose-Response Data (Carcinogenicity, Oral Exposure)

Tumor Type: hepatocellular carcinoma
Test animals: Mouse/B6CC3F1
Route: gavage
Reference: NCI, 1978

Administered
Dose (mg/kg)/day
Human Equivalent
Dose (mg/kg)/day
Tumor
Incidence
2 0 0/20
87 6.56 30/48
174 13.12 43/47

__II.B.3. Additional Comments (Carcinogenicity, Oral Exposure)

Administered doses are TWAs, adjusted for frequency (5/7 days) and length of exposure (546 days of an assumed lifespan of 637). Control group received vehicle (corn oil) by stomach tube. Weight of animals was assumed to be 0.030 kg. Human equivalent dose was adjusted by (0.03/70)**1/3 for body weight.

The unit risk should not be used if the water concentration exceeds 2E+3 ug/L, since above this concentration the unit risk may not be appropriate.

__II.B.4. Discussion of Confidence (Carcinogenicity, Oral Exposure)

An adequate number of animals was treated. Malignancies increased as a function of treatment dose, and their incidence was significantly increased at both doses.

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_II.C. Quantitative Estimate of Carcinogenic Risk from Inhalation Exposure

__II.C.1. Summary of Risk Estimates

Inhalation Unit Risk — 5.8E-5 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) 2E+0 ug/cu.m
E-5 (1 in 100,000) 2E-1 ug/cu.m
E-6 (1 in 1,000,000) 2E-2 ug/cu.m

__II.C.2. Dose-Response Data for Carcinogenicity, Inhalation Exposure

The inhalation risk estimates were calculated from the oral exposure data in II.B.2.

__II.C.3. Additional Comments (Carcinogenicity, Inhalation Exposure)

The unit risk should not be used if the air concentration exceeds 2E+2 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.

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_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 (1980) received extensive peer and public review.

__II.D.2. EPA Review (Carcinogenicity Assessment)

Agency Work Group Review — 06/26/1986

Verification Date — 06/26/1986

Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the cancer assessment for 1,1,2,2-Tetrachloroethane conducted in September 2002 did not identify any critical new studies. IRIS users who know of important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.

__II.D.3. EPA Contacts (Carcinogenicity Assessment)

Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).

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_III.  [reserved]
_IV.  [reserved]
_V.  [reserved]


_VI.  Bibliography

Substance Name — 1,1,2,2-Tetrachloroethane
CASRN — 79-34-5
Last Revised — 08/01/1989

_VI.A. Oral RfD References

None

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_VI.B. Inhalation RfD References

None

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_VI.C. Carcinogenicity Assessment References

Brem, H., A.B. Stein and H.S. Rosenkranz. 1974. The mutagenicity and DNA- modifying effect of halokanes. Cancer Res. 34: 2576-2579.

NCI (National Cancer Institute). 1978. Bioassay of 1,1,2,2,-Tetrachloro- ethane for possible carcinogenicity. U.S. Dept. Health, Education and Welfare. Pub. No. (NIH) 78-827).

Rosenkranz, H.S. 1977. Mutagenicity of halogenated alkanes and their derivaties. Environ. Health Perspect. 21: 79-84.

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 Regu- lations and Standards, Washington, DC. EPA 440/5-80-029. NTIS PB 81117400.

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_VII.  Revision History

Substance Name — 1,1,2,2-Tetrachloroethane
CASRN — 79-34-5

Date
Section
Description
03/01/1988 II.B.4. Confidence statement revised
03/01/1988 II.C.4. Confidence statement revised
03/01/1988 II.D.3. Secondary contact changed
08/01/1989 I.A. Oral RfD now under review
08/01/1989 VI. Bibliography on-line
01/01/1991 II. Text edited
01/01/1991 II.C.1. Inhalation slope factor removed (global change)
01/01/1992 IV. Regulatory Actions updated
02/01/1994 II.D.3. Primary contact's phone number changed
08/01/1995 I.A. EPA's RfD/RfC and CRAVE workgroups were discontinued in May, 1995. Chemical substance reviews that were not completed by September 1995 were taken out of IRIS review. The IRIS Pilot Program replaced the workgroup functions beginning in September, 1995.
04/01/1997 III., IV., V. Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were removed from IRIS on or before April 1997. IRIS users were directed to the appropriate EPA Program Offices for this information.
12/03/2002 II.D.2. Screening-Level Literature Review Findings message has been added.
03/07/2005 II.B.1. Text edited.

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_VIII.  Synonyms

Substance Name — 1,1,2,2-Tetrachloroethane
CASRN — 79-34-5
Last Revised — 03/31/1987

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