Hexabromobenzene (CASRN 87-82-1)
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0161
Hexabromobenzene;
CASRN 87-82-1
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 Hexabromobenzene
File First On-Line 03/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 03/01/1988* |
Inhalation RfC Assessment (I.B.) | no data | |
Carcinogenicity Assessment (II.) | no data |
*A comprehensive review of toxicological studies was completed 01/07/05 - 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)
— Hexabromobenzene
CASRN — 87-82-1
Last Revised — 03/01/1988
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
|
---|---|---|---|---|
Induced serum Rat Dietary Mendoza et al., 1977 |
NOAEL: 40 ppm diet (converted to 2 mg/kg/day) |
1000
|
1
|
2E-3
mg/kg/day |
Rat Preweanling and Primiparous Studies |
LOAEL: 80 ppm diet |
*Conversion Factors: Assumed rat food consumption = 5% bw/day
__I.A.2. Principal and Supporting Studies (Oral RfD)
Mendoza, C.E., H.M. Vijay, J.B. Shields and G.W. Laver. 1977. Effects of
hexabromobenzene on the male rat. Toxicol. Appl. Pharmacol. 41: 127-130.
Mendoza, C.E., B.T. Collins, J.B. Shields and G.W. Laver. 1978. Effects of
hexachlorobenzene or hexabromobenzene on body and organ weights of preweanling
rats after a reciprocal transfer between the treated and control dams. J.
Agric. Food Chem. 26: 941-945.
Mendoza, C.E., J.B. Shields and G.W. Laver. 1979. Comparison of the
porphyrinogenic activity of hexabromobenzene and hexachlorobenzene in
primiparous Wistar rats. Bull. Environ. Contam. Toxicol. 21: 358-364.
Mendoza et al. (1977) found no significant differences among control and
treated rats (adult male Wistar) in body or organ weights and for most
hematologic measurements. Rats were dosed at 0, 10, 20, 40, 80 or 160 ppm
hexabromobenzene (HBB) in the diet for 12 weeks. A statistically significant
induction of serum carboxylesterase activity was found at 40 ppm HBB and
higher. Although the study protocol apportioned eight rats to each treatment
group, a table indicated only four rats in the high-dose group. No
differences were found for liver esterase activity. Liver porphyrin levels
were not significantly increased in the treatment animals. Histopathology was
not performed.
Mendoza et al. (1978) reported increased liver-to-body weight ratios for
preweanling rats (Wistar) nursing on dams fed 80 ppm HBB in the diet during
the suckling period (17-21 days). This study used a cross-adoption design
involving two groups of 4 dams and 10 pups each. Half of the pups were
sacrificed at 17 days and the other half at 21 days. A complex statistical
model was presented. The effect was noted in the 17-day group, but not in the
21-day group. Ten dams (including four in the preweanling study) were fed HBB
at 80 ppm for a total of 101 days (Mendoza et al., 1979). A 1000-fold
difference in the level of porphyrins in the liver and elevated liver esterase
activity were found in the treated animals when compared to controls.
Liver/body weight ratio is an appropriate adverse effect since the liver is
the primary target organ of bromobenzenes in general. The mechanism of action
has been studied extensively, and involves conversion of the parent compound
to a reactive intermediate by hepatic microsomal enzymes. An increase in
serum carboxylesterase without concomitant liver enlargement or liver enzyme
induction is not considered adverse.
The LOAEL is conservative because of the uncertainty of the effects and the
probable higher food consumption of nursing dams (10% of body weight) compared
with the reference value (default) for adult rats (5% of body weight/day).
__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)
None.
__I.A.5. Confidence in the Oral RfD
Study — Low
Database — Low
RfD — Low
Although five dose levels were used in the critical study, the study was of short duration, only one sex was exposed, and few definitive parameters were examined. A question exists as to the number of animals/group as well. All supporting evidence is from the same laboratory. Other studies are mostly short-term and indicate a much higher toxicity threshold for HBB. Thus, confidence in the chosen study, database, and RfD are all considered low.
__I.A.6. EPA Documentation and Review of the Oral RfD
Source Document — U.S. EPA, 1984
The 1984 Health and Environmental Effects Profile for Bromobenzenes has
received Agency Review with the help of two outside scientists.
Other EPA Documentation — None
Agency Work Group Review — 10/09/1985, 11/06/1985
Verification Date — 11/06/1985
A comprehensive review of toxicological studies published through 2004 was conducted. No new health effects data were identified that would be directly useful in the revision of the existing RfD for Hexabromobenzene and a change in the RfD is not warranted at this time. For more information, IRIS users may contact 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 — Hexabromobenzene
CASRN — 87-82-1
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Hexabromobenzene
CASRN — 87-82-1
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 — Hexabromobenzene
CASRN — 87-82-1
Last Revised — 08/01/1989
_VI.A. Oral RfD References
Mendoza, C.E., H.M. Vijay, J.B. Shields and G.W. Laver. 1977. Effects of
hexabromobenzene on the male rat. Toxicol. Appl. Pharmacol. 41: 127-130.
Mendoza, C.E., B.T. Collins, J.B. Shields and G.W. Laver. 1978. Effects of
hexachlorobenzene or hexabromobenzene on body and organ weights of prewean-
ling rats after a reciprocal transfer between the treated and control dams.
J. Agric. Food Chem. 26: 941-945.
Mendoza, C.E., J.B. Shields and G.W. Laver. 1979. Comparison of the por-
phyrinogenic activity of hexabromobenzene and hexachlorobenzene in primipar-
ous Wistar rats. Bull. Environ. Contam. Toxicol. 21: 358-364.
U.S. EPA. 1984. Health and Environmental Effects Profile for Bromobenzenes.
Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste,
Washington, DC.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Hexabromobenzene
CASRN — 87-82-1
Date |
Section |
Description |
---|---|---|
03/01/1988 | I.A.1. | Dose conversion clarified |
08/01/1989 | VI. | Bibliography on-line |
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. |
03/03/2005 | I.A.6. | Screening-Level Literature Review Findings message has been removed and replaced by comprehensive literature review conclusions. |
_VIII. Synonyms
Substance Name — Hexabromobenzene
CASRN — 87-82-1
Last Revised — 03/31/1987