1,2,4-Tribromobenzene (CASRN 615-54-3)
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0196
1,2,4-Tribromobenzene;
CASRN 615-54-3
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-Tribromobenzene
File First On-Line 03/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 06/01/1993* |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
*A comprehensive review of toxicological studies was completed (2004) - please see section I.A.6 for more information.
_I. Chronic Health Hazard Assessments for Noncarcinogenic Effects
_I.A. Reference Dose for Chronic Oral Exposure (RfD)
Substance Name — 1,2,4-Tribromobenzene
CASRN — 615-54-3
Last Revised — 06/01/1993
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 |
---|---|---|---|---|
Increased liver-to- Rat Oral Subchronic Carlson and Tardiff, |
NOAEL: 5 mg/kg/day LOAEL: 10 mg/kg/day |
1000
|
1
|
5E-3
mg/kg/day |
*Conversion Factor and Assumptions -- None
__I.A.2. Principal and Supporting Studies (Oral RfD)
Carlson, G.P. and R.G. Tardiff. 1977. Effect of 1,4-dibromobenzene and
1,2,4-tribromobenzene on xenobiotic metabolism. Toxicol. Appl. Pharmacol.
42: 189-196.
Six male rats/group were dosed daily with 0, 2.5, 5 or 10 mg 1,2,4-
tribromobenzene (TBB)/kg bw for 45 or 90 days. TBB was administered in corn
oil p.o. as 0.1% of body weight. Controls received corn oil only. Animals
were sacrificed at 45 or 90 days or after an additional 30-day recovery period
after 90 days of treatment. Body weight, liver weight, and hepatic microsomal
enzyme activity were measured. Liver-to-body weight ratios were increased 12-
16% over controls for the rats treated at 10 mg/kg/day. Liver enzyme
activities were 1.4- to 3-fold that of controls for the same group. Full
recovery to baseline enzyme activity was observed after the 30-day recovery
period; liver-to-body weight ratios were only 7% greater than the control
values. Similar results were reported by Carlson (1979) in a follow-up study.
Although no overt liver toxicity was demonstrated for TBB, bromobenzene
mixtures at higher doses cause acute hepatic necrosis. The mechanism of
bromobenzene toxicity has been studied in detail and involves conversion of
the parent compound to toxic intermediates by hepatic microsomal enzymes.
Induction of these enzymes can potentiate the toxicity of bromobenzenes and
other similarly-activated compounds.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — The uncertainty factor includes factors for interspecies variability,
subchronic-to-chronic exposure duration extrapolation, and intrahuman
variability.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
None.
__I.A.5. Confidence in the Oral RfD
Study — Low
Database — Low
RfD — Low
Low confidence levels were assigned to both the study and the database because of the lack of adequate toxicity parameters in the critical study, the lack of chronic toxicity data in general, and a degree of uncertainty about the significance of the effects. Low confidence in the RfD follows.
__I.A.6. EPA Documentation and Review of the Oral RfD
Source Document — U.S. EPA, 1984
Other EPA Documentation — None
Agency Work Group Review — 10/09/1985, 05/15/1986
Verification Date — 05/15/1986
A comprehensive review of toxicological studies published prior to 2004 was conducted. No new health effects data were identified that would be directly useful in the revision of the existing RfD for 1,2,4-Tribromobenzene and a change in the RfD is not warranted at this time.
__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-Tribromobenzene
CASRN — 615-54-3
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — 1,2,4-Tribromobenzene
CASRN — 615-54-3
This substance/agent has not undergone a complete evaluation and determination under US EPA's IRIS program for evidence of human carcinogenic potential.
_III.
[reserved]
_IV. [reserved]
_V. [reserved]
_VI. Bibliography
Substance Name — 1,2,4-Tribromobenzene
CASRN — 615-54-3
Last Revised — 06/01/1993
_VI.A. Oral RfD References
Carlson, G.P. 1979. Brominated benzene induction of hepatic porphyria.
Experimentia. 35(4): 513-514.
Carlson, G.P. and R.G. Tardiff. 1977. Effect of 1,4-dibromobenzene and
1,2,4-tribromobenzene on xenobiotic metabolism. Toxicol. Appl. Pharmacol.
42: 189-196.
U.S. EPA. 1984. Health and Environmental Effects Profile for Bromobenzene.
Prepared by the Environmental Criteria and Assessment Office, Cincinnati, OH
for the Office of Solid Waste and Emergency Response, Washington, DC. NTIS
PB88-137757/AS.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — 1,2,4-Tribromobenzene
CASRN — 615-54-3
Date |
Section |
Description |
---|---|---|
06/01/1991 | VI. | Bibliography on-line |
06/01/1993 | I.A.6. | Source document corrected |
06/01/1993 | VI.A. | U.S. EPA, 1984 corrected |
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. |
09/29/2004 | I.A.6. | Screening-Level Literature Review Findings message has been removed and replaced by comprehensive literature review conclusions. |
_VIII. Synonyms
Substance Name — 1,2,4-Tribromobenzene
CASRN — 615-54-3
Last Revised — 03/31/1987
- 615-54-3
- Benzene, 1,2,4-tribromo- (8CI)(9CI)
- 1,2,4-Tribromobenzene
- Tribromobenzene, 1,2,4-