1,2,4,5-Tetrachlorobenzene (CASRN 95-94-3)
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0107
1,2,4,5-Tetrachlorobenzene;
CASRN 95-94-3
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 1,2,4,5-Tetrachlorobenzene
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 03/01/1991 |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — 1,2,4,5-Tetrachlorobenzene
CASRN — 95-94-3
Last Revised — 03/01/1991
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 |
---|---|---|---|---|
Kidney lesions Rat Oral Subchronic Chu et al., 1984 |
NOAEL: 5.0 ppm of diet LOAEL: 50 ppm of diet |
1000 |
1 |
3E-4 mg/kg/day |
*Conversion Factors: Dose conversions were reported by the authors.
__I.A.2. Principal and Supporting Studies (Oral RfD)
Chu, I., D.C. Villeneuve, V.E. Valli and V.E. Secours. 1984. Toxicity of
1,2,3,4-, 1,2,3,5- and 1,2,4,5-tetrachlorobenzene in the rat: Results of a 90-
day feeding study. Drug Chem. Toxicol. 7: 113-127.
Groups of 15/sex weanling Sprague-Dawley rats were fed diets containing 0,
0.5, 5.0, 50, and 500 ppm of 1,2,4,5-tetrachlorobenzene (TCB) for 13 weeks.
The corresponding dose range in mg/kg bw/day was given as 0.034-34. Dose-
related increases in the frequency and severity of kidney lesions for male
rats were observed at 1,2,4,5-TCB dose levels of 5.0 ppm and greater. The
severity of effects was considered significant only at the 50 and 500 ppm
levels because of a high incidence of mild kidney lesions in the controls.
Liver lesions were observed for female rats at 500 ppm.
A 28-day feeding study of 1,2,4,5-TCB in rats (10/sex/group) showed dose-
related effects for liver and kidney pathology at 3.4 and 32 mg/kg bw/day (Chu
et al., 1983). Liver lesions were reported as mild to moderately severe,
while kidney lesions were judged to be mild. Relative liver weight was
significantly increased (20-30%) at 32 mg/kg/day. Hepatic microsomal enzymes
were induced 2- to 12-fold at 32 mg/kg/day. Males were more susceptible than
females for all criteria. Adverse effects were not observed at two lower
doses (0.04 and 0.4 mg/kg/day).
Higher doses (50, 100, and 200 mg/kg/day) were associated with mortality (200
mg/kg/day only), elevated serum cholesterol, increased organ weights, and
liver enzyme induction when administered to pregnant rats for 10 days (Ruddick
et al., 1981).
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — The uncertainty factor of 1000 reflects 10 for both intraspecies and
interspecies variability to the toxicity of this chemical in lieu of specific
data, and 10 for extrapolation of a subchronic effect level to its chronic
equivalent.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
Braun et al. (1978) reported a NOAEL for dogs of 5 mg/kg bw/day for 1,2,4,5-
TCB administered in the diet for 2 years. Increased serum alkaline
phosphatase activity and increased liver weights were reported at 10 mg/kg
bw/day in a separate 144-day dog study referred to in Braun et al. (1978).
Both studies were unpublished and were judged inadequate for risk assessment.
The 2-year study was designed for other purposes and did not employ adequate
controls or timely histopathologic analysis.
A Russian study (Fomenko, 1965) reported impaired liver function and learning
response for rats and rabbits dosed orally for 8 months with 1,2,4,5-TCB at
0.005 or 0.05 mg/kg bw/day. A NOAEL of 0.001 mg/kg/day was established. The
study was judged unsuitable because of the lack of itemized data and detailed
study protocol.
NTP testing is in progress.
__I.A.5. Confidence in the Oral RfD
Study — Medium
Database — Low
RfD — Low
The principal study, although of short duration, is excellent in most respects (dose range, toxicologic criteria, data presentation, range of effects) except for the high incidence of kidney lesions in the control animals and a subsequent uncertainty in interpretation of effects. Thus, the confidence in the study is rated medium. The principal supporting study is of similar high quality, although shorter in duration. Effect levels are mutually supportive. However, the database lacks a bona fide chronic study and adequate reproductive and teratology bioassays. Thus, the database rates a low confidence. Low confidence in the RfD follows.
__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 — 10/09/1985, 11/06/1985
Verification Date — 11/06/1985
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfD for 1,2,4,5-Tetrachlorobenzene conducted in September 2002 identified one or more significant new studies. IRIS users may request the references for those studies from the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.
__I.A.7. EPA Contacts (Oral RfD)
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).
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — 1,2,4,5-Tetrachlorobenzene
CASRN — 95-94-3
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — 1,2,4,5-Tetrachlorobenzene
CASRN — 95-94-3
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_VI. Bibliography
Substance Name — 1,2,4,5-Tetrachlorobenzene
CASRN — 95-94-3
Last Revised — 03/01/1991
_VI.A. Oral RfD References
Braun, W.H., L.Y. Sung, D.G. Keyes and R.J. Kociba. 1978. Pharmacokinetic
and toxicological evaluation of dogs fed 1,2,4,5-tetrachlorobenzene in the
diet for two years. J. Toxicol. Environ. Health. 4: 727-734.
Chu, I., D.C. Villeneuve, V.E. Valli and V.E. Secours. 1984. Toxicity of
1,2,3,4-, 1,2,3,5- and 1,2,4,5-tetrachlorobenzene in the rat: Results of a
90-day feeding study. Drug Chem. Toxicol. 7: 113-127.
Chu, I., D.C. Villeneuve and V.E. Secours. 1984. Comparative toxicity of
1,2,3,4-, 1,2,4,5- and 1,2,3,5-tetrachlorobenzene in the rat: Results of acute
and subacute studies. J. Toxicol. Environ. Health. 11: 663-677.
Fomenko, V.N. 1965. Determination of the maximum permissible concentratin of
tetrachlorobenzene in water basins. Gig. Sanit. 30: 8-15.
Ruddick, J.A., D.C. Villeneuve, I. Chu, S. Kacew and V.E. Valli. 1981.
Transplacental and teratological evaluation of tetrachlorobenzene isomers in
the rat. Teratology. 23: 59A.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — 1,2,4,5-Tetrachlorobenzene
CASRN — 95-94-3
Date |
Section |
Description |
---|---|---|
03/01/1988 | I.A.1. | Dose conversion clarified |
03/01/1988 | I.A.5. | Confidence levels revised |
03/01/1988 | I.A.6. | Documentation corrected |
02/01/1989 | I.A.7. | Secondary contact's phone number corrected |
06/01/1990 | IV.A.1. | Area code for EPA contact corrected |
06/01/1990 | IV.F.1. | EPA contact changed |
03/01/1991 | I.A.4. | Fomenko, 1964 citation year corrected to 1965 |
03/01/1991 | VI. | Bibliography on-line |
01/01/1992 | IV. | Regulatory actions updated |
04/01/1992 | IV.A.1. | CAA regulatory action withdrawn |
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 | I.A.6. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — 1,2,4,5-Tetrachlorobenzene
CASRN — 95-94-3
Last Revised — 01/31/1987
- 95-94-3
- BENZENE, 1,2,4,5-TETRACHLORO-
- RCRA WASTE NUMBER U207
- 1,2,4,5-Tetrachlorobenzene
- Tetrachlorobenzene, 1,2,4,5-