#ll.	United States
Environmental Protection
^^LbI M % Agency
EPA/690/R-06/015F
Final
7-31-2006
Provisional Peer Reviewed Toxicity Values for
1,2-Dinitrobenzene (o-Dinitrobenzene)
(CASRN 528-29-0)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

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Acronyms and Abbreviations
bw	body weight
cc	cubic centimeters
CD	Caesarean Delivered
CERCLA	Comprehensive Environmental Response, Compensation and Liability Act
of 1980
CNS	central nervous system
cu.m	cubic meter
DWEL	Drinking Water Equivalent Level
FEL	frank-effect level
FIFRA	Federal Insecticide, Fungicide, and Rodenticide Act
g	grams
GI	gastrointestinal
HEC	human equivalent concentration
Hgb	hemoglobin
i.m.	intramuscular
i.p.	intraperitoneal
IRIS	Integrated Risk Information System
IUR	inhalation unit risk
i.v.	intravenous
kg	kilogram
L	liter
LEL	lowest-effect level
LOAEL	lowest-observed-adverse-effect level
LOAEL(ADJ)	LOAEL adjusted to continuous exposure duration
LOAEL(HEC)	LOAEL adjusted for dosimetric differences across species to a human
m	meter
MCL	maximum contaminant level
MCLG	maximum contaminant level goal
MF	modifying factor
mg	milligram
mg/kg	milligrams per kilogram
mg/L	milligrams per liter
MRL	minimal risk level
MTD	maximum tolerated dose
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MTL
median threshold limit
NAAQS
National Ambient Air Quality Standards
NOAEL
no-observed-adverse-effect level
NOAEL(ADJ)
NOAEL adjusted to continuous exposure duration
NOAEL(HEC)
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-observed-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional inhalation reference concentration
p-RfD
provisional oral reference dose
PBPK
physiologically based pharmacokinetic
PPb
parts per billion
ppm
parts per million
PPRTV
Provisional Peer Reviewed Toxicity Value
RBC
red blood cell(s)
RCRA
Resource Conservation and Recovery Act
RDDR
Regional deposited dose ratio (for the indicated lung region)
REL
relative exposure level
RfC
inhalation reference concentration
RfD
oral reference dose
RGDR
Regional gas dose ratio (for the indicated lung region)
s.c.
subcutaneous
SCE
sister chromatid exchange
SDWA
Safe Drinking Water Act
sq.cm.
square centimeters
TSCA
Toxic Substances Control Act
UF
uncertainty factor
Hg
microgram
|j,mol
micromoles
voc
volatile organic compound
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PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR
1,2-DINITROBENZENE (o-DINITROBENZENE) (CASRN 528-29-0)
Background
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) Office of
Superfund Remediation and Technology Innovation (OSRTI) revised its hierarchy of human
health toxicity values for Superfund risk assessments, establishing the following three tiers as the
new hierarchy:
1.	EPA's Integrated Risk Information System (IRIS).
2.	Provisional Peer-Reviewed Toxicity Values (PPRTV) used in EPA's Superfund
Program.
3.	Other (peer-reviewed) toxicity values, including:
~	Minimal Risk Levels produced by the Agency for Toxic Substances and Disease
Registry (ATSDR),
~	California Environmental Protection Agency (CalEPA) values, and
~	EPA Health Effects Assessment Summary Table (HEAST) values.
A PPRTV is defined as a toxicity value derived for use in the Superfund Program when
such a value is not available in EPA's Integrated Risk Information System (IRIS). PPRTVs are
developed according to a Standard Operating Procedure (SOP) and are derived after a review of
the relevant scientific literature using the same methods, sources of data, and Agency guidance
for value derivation generally used by the EPA IRIS Program. All provisional toxicity values
receive internal review by two EPA scientists and external peer review by three independently
selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the
multi-program consensus review provided for IRIS values. This is because IRIS values are
generally intended to be used in all EPA programs, while PPRTVs are developed specifically for
the Superfund Program.
Because science and available information evolve, PPRTVs are initially derived with a
three-year life-cycle. However, EPA Regions or the EPA Headquarters Superfund Program
sometimes request that a frequently used PPRTV be reassessed. Once an IRIS value for a
specific chemical becomes available for Agency review, the analogous PPRTV for that same
chemical is retired. It should also be noted that some PPRTV manuscripts conclude that a
PPRTV cannot be derived based on inadequate data.
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Disclaimers
Users of this document should first check to see if any IRIS values exist for the chemical
of concern before proceeding to use a PPRTV. If no IRIS value is available, staff in the regional
Superfund and RCRA program offices are advised to carefully review the information provided
in this document to ensure that the PPRTVs used are appropriate for the types of exposures and
circumstances at the Superfund site or RCRA facility in question. PPRTVs are periodically
updated; therefore, users should ensure that the values contained in the PPRTV are current at the
time of use.
It is important to remember that a provisional value alone tells very little about the
adverse effects of a chemical or the quality of evidence on which the value is based. Therefore,
users are strongly encouraged to read the entire PPRTV manuscript and understand the strengths
and limitations of the derived provisional values. PPRTVs are developed by the EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center for OSRTI. Other EPA programs or external parties who may
choose of their own initiative to use these PPRTVs are advised that Superfund resources will not
generally be used to respond to challenges of PPRTVs used in a context outside of the Superfund
Program.
Questions Regarding PPRTVs
Questions regarding the contents of the PPRTVs and their appropriate use (e.g., on
chemicals not covered, or whether chemicals have pending IRIS toxicity values) may be directed
to the EPA Office of Research and Development's National Center for Environmental
Assessment, Superfund Health Risk Technical Support Center (513-569-7300), or OSRTI.
This document has passed the STSC quality review and peer review evaluation indicating
that the quality is consistent with the SOPs and standards of the STSC and is suitable for use by
registered users of the PPRTV system.
INTRODUCTION
The HEAST (U.S. EPA, 1997) lists a subchronic RfD of 4E-3 mg/kg-day and a chronic
RfD of 4E-4 mg/kg-day for 1,2-dinitrobenzene derived by analogy to 1,3-dinitrobenzene
(m-dinitrobenzene). The assessment for 1,3-dinitrobenzene was based on a subchronic NOAEL
of 0.4 mg/kg-day and LOAEL of 1.1 mg/kg-day for increased splenic weight in rats, and included
an uncertainty factor (UF) of 100 (10 for extrapolation from animal data and 10 for sensitive
individuals) for the subchronic RfD, and 1000 (including an additional UF of 10 for the use of a
subchronic study) for the chronic RfD. The source document was a Health and Environmental
Effects Profile (HEEP) for dinitrobenzenes (U.S. EPA, 1985) that derived a chronic allowable
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daily intake (ADI) for 1,2-dinitrobenzene by analogy equal to the chronic ADI for 1,3-
dinitrobenzene. Because the HEAST derivations did not employ UFs for database deficiencies,
the RfDs for 1,2-dinitrobenzene in the HEAST are higher than the current RfD for 1,3-
dinitrobenzene on IRIS (1E-4 mg/kg-day), which added a database uncertainty factor of 3 (total
UF = 3000) to the previous assessment (U.S. EPA, 2006). The HEAST (U.S. EPA, 1997) does
not list an RfC or cancer assessment for 1,2-dinitrobenzene. On IRIS (U.S. EPA, 2006),
1,2-dinitrobenzene is assigned to cancer weight-of-evidence Group D, not classifiable as to
human carcinogenicity, based on a lack of evidence in humans or animals by any route of
exposure and negative results in a few bacterial genotoxicity assays. This assessment was
derived in a Health and Environmental Effects Document (HEED) for dinitrobenzenes (U.S.
EPA, 1991a). 1,2-Dinitrobenzene is not listed on the Drinking Water Standards and Health
Advisories list (U.S. EPA, 2000). Aside from the HEEP, no additional relevant documents are
included in the CARA list (U.S. EPA, 1991b, 1994).
ACGIH (2001a,b) established a TLV-TWA of 0.15 ppm (1 mg/m3) for all three isomers
of dinitrobenzene to protect against anoxia resulting from methemoglobin formation. The
TLV-TWA also includes a note recognizing that all three isomers are readily absorbed through
the skin. This value was based on the TLV-TWA of 2 ppm (7.6 mg/m3) for aniline (ACGIH,
2001c) and the relatively higher methemoglobin-producing capacity of dinitrobenzenes compared
to aniline. The NIOSH (2002) REL-TWA for 1,2-dinitrobenzene is also 1 mg/m3 with a skin
notation to protect against methemoglobinemia and effects on the liver, cardiovascular system,
eyes, skin and central nervous system. OSHA (2002a,b) established a PEL-TWA of 1 mg/m3
with a skin notation for all dinitrobenzenes to protect against the same effects and, in addition,
kidney damage.
ATSDR (2002) and the WHO (2002) have not published toxicological reviews on 1,2-
dinitrobenzene; ATSDR (1995) published a toxicological profile on 1,3-dinitrobenzene, but this
document has no information about 1,2-dinitrobenzene. IARC (2002) and the NTP (2002) have
not evaluated the carcinogenicity of 1,2-dinitrobenzene. Toxicity reviews on aromatic nitro
compounds (Benya and Cornish, 1994; Weisburger and Hudson, 2001) were consulted for
relevant information. Literature searches were conducted for the period from 1984 to December
2001 to identify data relevant for the derivation of a provisional RfD, RfC and cancer assessment
for 1,2-dinitrobenzene. The following databases were searched: TOXLINE, MEDLINE,
CANCERLIT, TOXLIT/BIOSIS, RTECS, HSDB, GENETOX, CCRIS, TSCATS,
EMIC/EMICBACK and DART/ETICBACK.
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REVIEW OF THE PERTINENT LITERATURE
Human Studies
No data were located regarding oral exposure of humans to 1,2-dinitrobenzene or
subchronic or chronic inhalation exposure of humans to 1,2-dinitrobenzene where the levels of
exposure were known. In general, occupational incidents involved combined inhalation and
dermal exposure and exposure levels were not reported (ACGIH, 2001b). Cyanosis and
methemoglobinemia were the major reported health effects. Following chronic exposures to
dinitrobenzenes, anemia and sometimes hepatic injury, impaired vision, and yellow discoloration
of the conjunctiva and sclera of the eye were observed.
Animal Studies
No data were located on the toxicity of 1,2-dinitrobenzene to animals following chronic
or subchronic oral or inhalation exposure.
Similarity to 1,3-Dinitrobenzene
Data on physical and chemical properties, pharmacokinetics and acute effects suggest that
toxic effects from chronic oral exposure to 1,2-dinitrobenzene will be similar to that of 1,3-
dinitrobenzene, although the 1,2- isomer appears to be less potent. The physical and chemical
properties of the two isomers are generally similar, except that the 1,2-isomer is considerably
more soluble in water (Table 1).
Pharmacokinetic data suggest a similar fate for all of the dinitrobenzenes in mammalian
systems (U.S. EPA, 1991a). Gavage studies of dinitrobenzenes in rats and rabbits showed a high
degree of absorption by the gastrointestinal tract and urinary excretion as the major route of
elimination; significant biliary excretion was reported.. In rabbits gavaged with single doses of
50-100 mg/kg of 1,3-dinitro-[14C]-benzene, absorption was >95% of the dose. Recovery of
radioactivity over 48 hours accounted for 65-93% of the dose in urine and <5% in feces. In rats
given single doses of 25.2 mg/kg of radiolabeled isomer, absorption was at least 92.4% for 1,2-
dinitrobenzene, 82.6% for 1,3-dinitrobenzene and 91.3% for 1,4-dinitrobenzene. Over 48 hours,
radioactivity in urine accounted for 81.3, 63.2 and 75.1%> of the dose, and in feces, 7.6, 17.4 and
8.7%) of the dose for 1,2-, 1,3- and 1,4-dinitrobenzene, respectively.
Analysis of urinary metabolites in rats gavaged with dinitrobenzenes revealed some
differences in metabolic pathways (U.S. EPA, 1991a; Benya and Cornish, 1994). The major
urinary metabolites of 1,2-dinitrobenzene were S-(2-nitrophcnyl)-A,'-acctylcystcinc (42%), 2-
nitroanilinc-A'-glucuronide (4%), 2-amino-3-nitrophenyl sulfate (1.5%) and 2-(N-
hydroxylamine)-nitrobenzene (1-2%). The major urinary metabolites of 1,3-dinitrobenzene
were 3-aminoacetanilide (22%), 4-acetamidophenyl sulfate (6%), 1,3-diacetamidobenzene (7%)
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Table 1. Selected Properties of Dinitrobenzenes (U.S. EPA, 1985, 1991a; O'Neil et al., 2001)
Physical Property
1,2-Dinitrobenzene
1,3-Dinitrobenzene
Physical state
white crystals
yellowish crystals
Melting point °C
117.9
89.9
Boiling point °C
319 (at 773 mm Hg)
291 (at 756 mm Hg)
Specific gravity
1.565
1.546
Vapor pressure (mm Hg)
1.60 x 10"4
2.23 x 10"4
Water solubility (mg/L)
2100 at 25°C
500 at 25°C
Log octanol/water partition
coefficient
1.58
1.49
and 3-nitroanilinc-A''-glucuronidc. The major urinary metabolites of 1,4-dinitrobenzene were 2-
amino-5-nitrophenyl sulfate (35%), S-(4-nitrophcnyl)-/V-acctylcystcinc (13%) and 1,4-
diacetamidobenzene (7%). These results indicate that 1,3-dinitrobenzene was metabolized
exclusively by reduction of the nitro groups to amines, which were subsequently acetylated. No
direct conjugation to glutathione was detected for 1,3-dinitrobenzene, whereas that process was
the major metabolic pathway for 1,2-dinitrobenzene. 1,4-Dinitrobenzene was metabolized by
both of these pathways, but its major pathway involved reduction of a nitro group followed by
hydroxylation of the phenyl ring and sulfate conjugation of the phenol.
Comparative in vitro analysis of the metabolites in rat erythrocytes or hepatocytes
exposed for 30 minutes also demonstrated differences and similarities among the isomers (U.S.
EPA,1991a; Rickert, 1987). In erythrocytes, 37% of added 1,2-dinitrobenzene was conjugated to
glutathione and 24% was conjugated to macromolecules. In erythrocytes treated with 1,3-
dinitrobenzene, no metabolites were detected, but 2% was covalently bound to macromolecules.
In erythrocytes treated with 1,4-dinitrobenzene, 6% was conjugated to glutathione, 10% was
reduced to 4-nitrophenylhydroxylamine and 40% was covalently bound to erythrocyte
macromolecules. In hepatocytes, a significant proportion of all three isomers was converted to
the related nitroaniline (30% 2-nitroaniline, 74% 3-nitroaniline and 81% 4-nitroaniline) and no
covalent binding of any isomer was detected. Glutathione conjugation represented 48% of the
1,2-dinitrobenzene added to rat hepatocytes. These experiments indicate that all dinitrobenzene
isomers, to some degree, covalently bind to macromolecules in erythrocytes and are metabolized
to another methemoglobin-producing compound (nitroaniline) in the liver (see below).
Acute oral exposure to dinitrobenzene isomers causes methemoglobinemia in humans
and animals (U.S. EPA, 1985, 1991a). An acute oral LD0 of 28 mg/kg has been reported for 1,3-
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dinitrobenzene in humans (U.S. EPA, 1991 a). The acute oral LD0s in rats were 250, 27 and 29
mg/kg for 1,2-, 1,3- and 1,4-dinitrobenzene, respectively (Watanabe et al., 1976; U.S. EPA,
1991a). In rats injected i.p. with 100 |iM dinitrobenzene isomer, methemoglobin levels five
hours after injection were 13.1, 25.5 and 29.5% for 1,2-, 1,3- and 1,4-dinitrobenzene,
respectively (Watanabe et al., 1976). In single-dose studies in rats, treatment with > 16 mg/kg of
1,3-dinitrobenzene caused testicular lesions that were not caused by the other dinitrobenzenes
(U.S. EPA, 1991a).
In vitro studies demonstrated that 1,4-dinitrobenzene was about ten times more potent
than 1,2-dinitrobenzene in inducing methemoglobin formation in freshly-drawn sheep
erythrocytes (French et al., 1995); 1,3-dinitrobenzene was not effective in sheep erythrocytes.
Methemoglobin levels about four times higher than control were produced by treatment with
0.005 mM 1,4-dinitrobenzene or 0.05 mM 1,2-dinitrobenzene. The related nitroanilines were
also significant inducers of methemoglobin formation, but their effect required the presence of an
NADP bioactivation system. 4-Nitroaniline was more potent than 2- or 3-nitroaniline;
approximately four-fold increases in methemoglobin were induced by 0.005 mM 4-nitroaniline,
0.25 mM 3-nitroaniline or 0.05 mM 2-nitroaniline.
The available in vitro evidence suggests that 1,2-dinitrobenzene is less genotoxic than
1,3-dinitrobenzene (U.S. EPA, 1985, 1991a). Neither isomer induced reverse mutations in
Salmonella typhimurium strains TA1537 or TA100NR3 (nitroreductase-deficient) with or
without metabolic activation. 1,2-Dinitrobenzene did not induce reverse mutations in TA98,
TA1535 or TA1538 with or without metabolic activation, or in strain TA100 without activation,
whereas 1,3-dinitrobenzene generally tested positive in these strains (U.S. EPA, 1985, 1991a).
Positive results occurred when strain TA100 was tested with 1,2-dinitrobenzene in the presence
of S9 from Kanechlor 500-induced rat liver (Kawai et al., 1987); S9 from Arochlor-induced rat
liver was not effective (U.S. EPA, 1991a; Assmann et al., 1997). 1,2-Dinitrobenzene, as well as
the 1,3- and 1,4- isomers, induced chromosomal aberrations in peripheral lymphocytes obtained
from a human male donor (Huang et al., 1996); in this study, all three isomers tested positive at
concentrations of > 1 mmol/1.
DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
ORAL RfD VALUES FOR 1,2-DINITROBENZENE
BY ANALOGY TO 1,3-DINITROBENZENE
No data are available for the chronic or subchronic oral toxicity of 1,2-dinitrobenzene in
humans or animals. However, a chronic RfD of 1E-4 mg/kg-day is available for
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1,3-dinitrobenzene on IRIS (U.S. EPA, 2006) and a related subchronic RfD1 of 1E-3 is available
for 1,3-dinitrobenzene in the HEAST (U.S. EPA, 1997). The chronic RfD was based on
increased splenic weight (apparently secondary to erythrocyte effects) in rats treated with 8 ppm
of 1,3-dinitrobenzene in drinking water for 16 weeks (Cody et al., 1981). The chronic RfD for
1,3-dinitrobenzene was calculated by applying an uncertainty factor of 3000 (10 for extrapolation
from rats to humans, 10 to protect sensitive individuals, 10 for the use of a subchronic study, and
3 for database deficiencies) to the NOAEL of 0.4 mg/kg-day (3 ppm).
In order to derive an oral p-RfD for 1,2-dinitrobenzene by analogy to 1,3-dinitrobenzene,
the two isomers must be sufficiently similar in physical properties, fate in the body and nature of
their toxic effects to justify the extrapolation. This is largely a matter of judgement. As noted
above, the physical and chemical properties are similar for 1,2-dinitrobenzene and 1,3-
dinitrobenzene, and both compounds have the ability to convert hemoglobin to methemoglobin.
Although there are slight differences in pharmacokinetic pathways, the major hepatic metabolites
(nitroanilines) of both compounds are also methemoglobin-producing. The apparent higher acute
toxicity of 1,3-dinitrobenzene suggests that RfDs based on 1,3-dinitrobenzene will be sufficiently
protective for exposures to 1,2-dinitrobenzene. Therefore, the chronic RfD of 1E-4 mg/kg-day
for 1,3-dinitrobenzene on IRIS (U.S. EPA, 2006) is adopted as the chronic p-RfD for 1,2-
dinitrobenzene. The subchronic p-RfD for 1,2-dinitrobenzene is derived by eliminating the
uncertainty factor of 10 for use of the subchronic study, resulting in a subchronic p-RfD of 1E-3
mg/kg-day for 1,2-dinitrobenzene. These p-RfD values are lower than those in the HEAST
(U.S. EPA, 1997) because the new derivations include uncertainty factors for data base
deficiencies.
Confidence in the subchronic and chronic p-RfDs for 1,2-dinitrobenzene is low, as no
relevant studies were located and the p-RfDs were derived by analogy to the 1,3-dinitrobenzene
isomer.
DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC
INHALATION RfC VALUES FOR 1,2-DINITROBENZENE
No data are available for the chronic or subchronic inhalation toxicity of 1,2-
dinitrobenzene in humans or animals. In addition, no information is available for 1,3-
dinitrobenzene or 1,4-dinitrobenzene. In the absence of compound-specific data or data on close
analogs, it is not feasible to derive subchronic or chronic p-RfCs for 1,2-dinitrobenzene.
1 The HEAST (1997) misstates the uncertainty factor for the subchronic RfD for 1,3-dinitrobenzene; it was
300 and not 100.
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DERIVATION OF A PROVISIONAL CARCINOGENICITY ASSESSMENT
FOR 1,2-DINITROBENZENE
No human or animal carcinogenicity data were located for 1,2-dinitrobenzene. In vitro
genotoxicity data indicate that this chemical is not mutagenic in bacteria without bioactivation,
but that it may induce chromosomal aberrations in human lymphocytes. Under the U.S. EPA
(2005) cancer guidelines, the available data are inadequate for an assessment of human
carcinogenic potential.
Derivation of quantitative estimates of cancer risk for 1,2-dinitrobenzene is precluded by
the absence of carcinogenicity data.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). 2001a. Threshold limit
values (TLV) for chemical substances and physical agents and biological exposure indices.
ACGIH, Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hygienists). 2001b. Dinitrobenzene
(All Isomers). Documentation of the Threshold Limit Values and Biological Exposure Indices,
7th Ed. ACGIH, Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hygienists). 2001c. Aniline.
Documentation of the Threshold Limit Values and Biological Exposure Indices, 7th ed. ACGIH,
Cincinnati, OH.
Assmann, N., M. Emmrich, G. Kampf and M. Kaiser. 1997. Genotoxic activity of important
nitrobenzenes and nitroanilines in the Ames test and their structure-activity relationship.
Mutat. Res. 395:139-144. [CCRIS entry]
ATSDR (Agency for Toxic Substances and Disease Registry). 1995. Toxicological Profile for
1,3-Dinitrobenzene and 1,3,5-Trinitrobenzene. PB 95/264289/AS.
ATSDR (Agency for Toxic Substances and Disease Registry). 2002. Internet HazDat-
Toxicological Profile Query. Online, www.atsdr.cdc.gov/gsq 1/toxprof.script
Benya, T.J. and H.H. Cornish. 1994. Aromatic nitro and amino compounds. In: Patty's
Toxicology, 4th ed. Vol. 2, Part B. G.D. Clayton and F.E. Clayton, Ed. John Wiley and Sons,
New York. p. 947-1055.
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Cody, T.E., S. Witherup, L. Hastings et al. 1981. 1,3-Dinitrobenzene: toxic effects in vivo and
in vitro. J. Toxicol. Environ. Health. 7: 829-847.
French, C.L., S.-S. Yaun, L.A. Baldwin et al. 1995. Potency ranking of methemoglobin-forming
agents. J. Appl. Toxicol. 15: 167-174.
Huang, Q,-G., L.-R. Kong, Y.-B. Liu and L.-S. Wang. 1996. Relationship between molecular
structure and chromosomal aberrations in in vitro human lymphocytes induced by substituted
nitrobenzenes. Bull. Environ. Contam. Toxicol. 57: 349-353.
IARC (International Agency for Research on Cancer). 2002. Search I ARC agents and summary
evaluations. Online, http://monographs.iarc.fir/
Kawai, A., S. Goto, U. Matsumoto and H. Matsushita. 1987. Mutagenicity of aliphatic and
aromatic nitro compounds. Jpn. J. Ind. Health. 29: 34-54. [CCRIS entry]
NIOSH (National Institute for Occupational Safety and Health). 2002. o-Dinitrobenzene.
CASRN 528-29-0. NIOSH Pocket Guide to Chemical Hazards. Online.
www.cdc.gov/niosh/npg/npgd0231.html
NTP (National Toxicology Program). 2002. Website search engine. Online.
http://ntp-server.niehs.nih.gov/cgi/iH Indexes/ALL SRCH/iH ALL SRCH Frames.html
O'Neil, M.J., A. Smith, and P.E. Heckelman, Ed. 2001. The Merck Index. 13th ed. Merck &
Co., Inc., Whitehouse Station, New Jersey. 3299 p.
OSHA (Occupational Safety and Health Administration). 2002a. Chemical Sampling
Information for Dinitrobenzene (All Isomers). Online.
http://www.osha-slc.gov/dts/chemicalsampling/data/CH 236600.html
OSHA (Occupational Safety and Health Administration). 2002b. Occupational safety and health
guideline for dinitrobenzene (all isomers). Online.
http://www. ¦Osha-slc.gov/SLTC/healthguidelines/dinitrobenzeneallisomers/recognition.html
Rickert, D.E. 1987. Metabolism of nitroaromatic compounds. Drug Metab. Rev. 18:25-53.
U.S. EPA. 1985. Health and Environmental Effects Profile (HEEP) for Dinitrobenzenes (o-, m-,
p-). 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. September.
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U.S. EPA. 1991a. Health and Environmental Effects Document (HEED) for 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. October.
U.S. EPA. 1991b. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. April.
U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and
Environmental Assessment, Washington, DC. December.
U.S. EPA. 1997. Health Effects Assessment Summary Tables (HEAST). FY-1997 Update.
Prepared by the Office of Research and Development, National Center for Environmental
Assessment, Cincinnati, OH, for the Office of Emergency and Remedial Response, Washington,
DC. July. EPA/540/R-97/036. NTIS PB 97-921199.
U.S. EPA. 2000. Drinking Water Standards and Health Advisories. Office of Water,
Washington, DC. Summer 2000. EPA/822/B-00/001. Online.
www.epa.gov/ost/drinking/standards/dwstandards.pdf
U.S. EPA. 2005. Guidelines for Carcinogen Risk Assessment. Office of Research and
Development, National Center for Environmental Assessment, Washington, DC.
EPA/63 0/P-03/001F.
U.S. EPA. 2006. Integrated Risk Information System (IRIS). Office of Research and
Development, National Center for Environmental Assessment, Washington, DC. Online.
www.epa.gov/iris
Watanabe, T., N. Ishihara and M. Ikeda. 1976. Toxicity of and biological monitoring for 1,3-
diamino-2,4,6-trinitrobenzene and other nitro-amino derivatives of benzene and chlorobenzene.
Int. Arch. Occup. Environ. Health. 37: 157-168.
Weisburger, E.K. and V.W. Hudson. 2001. Aromatic nitro and amino compounds. In: Patty's
Toxicology, 5th ed. Vol. 4, E. Bingham, B. Cohrssen and C.H. Powell, Ed. John Wiley and
Sons, New York. p. 817-968.
WHO (World Health Organization). 2002. Online catalogs for the Environmental Health
Criteria series. Online, www.who.int/dsa/cat97/zehc.htm and
www.who.int/dsa/iustpub/add.htm
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