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o-Dinitrobenzene
CASRN 528-29-0
Contents
0633
o-Dinitrobenzene; CASRN 528-29-0
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 o-Dinitrobenzene
File On-Line 09/01/1992
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) no data
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) on-line 12/01/1996
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- o-Dinitrobenzene
CASRN -- 528-29-0
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- o-Dinitrobenzene
CASRN -- 528-29-0
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- o-Dinitrobenzene
CASRN -- 528-29-0
Last Revised -- 12/01/1996
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 -- D; not classifiable as to human carcinogenicity
Basis -- Based on no data in humans and animals.
___II.A.2. HUMAN CARCINOGENICITY DATA
None.
___II.A.3. ANIMAL CARCINOGENICITY DATA
None.
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
Data are not available regarding the carcinogenicity of any dinitrobenzene
isomers (i.e., o-, m- or p-dinitrobenzene) in humans or animals by any route
of exposure.
In the only available evaluation of o-dinitrobenzene mutagenicity, no
reverse mutations were observed in Salmonella typhimurium strains TA1535,
TA1538, TA98, TA100 or TA100NR3 with or without metabolic activation with rat
liver S9 fractions (Spanggord et al., 1982). Spanggord et al. (1982) also
reported that p-dinitrobenzene was not mutagenic in the same strains, but
Probst et al. (1981) reported mutagenic activity in strains TA1535, TA1538 and
TA98 following exposure to p-dinitrobenzene.
In contrast, m-dinitrobenzene was mutagenic with or without metabolic
activation in strains TA1538, TA98 and TA100, but not in TA100NR3, TA1535 or
TA1537 (Spanggord et al., 1982). Other tests have observed mutagenic
responses to m-dinitrobenzene in Salmonella typhimurium (McGregor et al.,
1980; Chiu et al., 1978; Garner and Nuttman, 1977; Matsuda, 1981; Probst et
al., 1981). It has been suggested that the lack of mutagenicity in strain
TA100NR3 (a nitro-reductase-deficient strain) indicates that nitro-reduction
may be required for the expression of m-dinitrobenzene genotoxicity (Spanggord
et al., 1982).
Qualitative and quantitative differences in the metabolic pathways of the
dinitrobenzenes have been observed in rats (Nystrom and Rickert, 1987). Direct
conjugation with glutathione appeared to be the most important pathway for o-
dinitrobenzenes; pathways involving reduction of the nitro groups appeared to
be of secondary importance. Radioactivity in urinary S-(2-nitrophenyl)-N-
acetylcysteine accounted for 42% of administered radiolabeled o-dinitrobenzene
in rats. In contrast, no evidence was observed for direct conjugation of m-
dinitrobenzene with glutathione; the significant pathways for m-dinitrobenzene
in rats involved initial reduction of the nitro groups followed by acetylation
of the resulting amino groups. Analysis of urinary metabolites indicated that
both pathways (i.e., reduction of nitro groups and direct conjugation with
glutathione) operated in rats following exposure to p-dinitrobenzene (Nystrom
and Rickert, 1987).
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
None.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
None.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1991
The 1991 Health and Environmental Effects Document for Dinitrobenzenes (draft)
has received Agency review.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 04/02/1992
Verification Date -- 04/02/1992
___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 -- o-Dinitrobenzene
CASRN -- 528-29-0
Last Revised -- 09/01/1992
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Chiu, C.W., L.H. Lee, C.Y. Wang and G.T. Bryan. 1978. Mutagenicity of some
commercially available nitro compounds for Salmonella typhimurium. Mutat.
Res. 58: 11-22.
Garner, R.C. and C.A. Nutman. 1977. Testing of some azo dyes and their
reduction products for mutagenicity using Salmonella typhimurium TA1538.
Mutat. Res. 44: 9-19.
Matsuda, A. 1981. Studies on the mutagenicity of nitroaromatic compounds in
environment. Gifu Daigaku Igakubu Kiyo. 29(2): 278-296.
McGregor, D.B., C.G. Riach, R.M. Hastwell and J.C. Dacre. 1980. Genotoxic
activity in microorganisms of tetryl, 1,3-dinitrobenzene and 1,3,5-
trinitrobenzene. Environ. Mutagen. 2(4): 531-541.
Nystrom, D.D. and D.E. Rickert. 1987. Metabolism and excretion of
dinitrobenzenes by male Fischer-344 rats. Drug Metab. Dispos. 15(6):
821-825.
Probst, G.S., R.E. McMahon, L.E. Hill, C.Z. Thompson, J.K. Epp and S.B. Neal.
1981. Chemically-induced unscheduled DNA synthesis in primary rat hepatocyte
cultures: A comparison with bacterial mutagenicity using 218 compounds.
Environ. Mutagen. 3(1): 11-32.
Spanggord, R.J., K.E. Mortelmans, A.F. Griffin and V.F. Simmon. 1982.
Mutagenicity in Salmonella typhimurium and structure-activity relationships of
waste water components emanating from the manufacture of trinitrotoluene.
Environ. Mutagen. 4(2): 163-179.
U.S. EPA. 1991. Health and Environmental Effects Document on
Dinitrobenzenes. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Solid Waste and Emergency Response, Washington, DC. (Draft)
_VII. REVISION HISTORY
Substance Name -- o-Dinitrobenzene
CASRN -- 528-29-0
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
05/01/1992 II. Carcinogenicity assessment now under review
06/01/1992 Synonyms Synonyms added
09/01/1992 II. Carcinogenicity assessment on-line
09/01/1992 VI. Bibliography on-line
07/01/1993 II.D.1. Other EPA Documentation heading removed
12/01/1996 II.D.3. Primary contact removed
VIII. SYNONYMS
Substance Name -- o-Dinitrobenzene
CASRN -- 528-29-0
Last Revised -- 06/01/1992
528-29-0
Benzene, 1,2-dinitro-
AI3-15338
Benzene, o-dinitro-
HSDB 4486
o-dinitrobenzene
1,2-Dinitrobenzene
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0633.HTM
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