United States Environmental Protection 1=1 m m Agency EPA/690/R-06/016F Final 6-16-2006 Provisional Peer Reviewed Toxicity Values for 1,4-Dinitrobenzene (/?-Dinitrobenzene) (CASRN 100-25-4) Superfund Health Risk Technical Support Center National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati, OH 45268 ------- 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 1 ------- 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 11 ------- 06-16-2006 PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR 1,4-DINITROBENZENE (p-DINITROBENZENE) (CASRN 100-25-4) 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. 1 ------- 06-16-2006 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 1,4-dinitrobenzene derived by analogy to 1,3-dinitrobenzene. The assessment for 1,3-dinitrobenzene (m-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 2 ------- 06-16-2006 daily intake (ADI) for 1,4-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 1,4-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 1,4-dinitrobenzene. However, a Health and Environmental Effects Document (HEED) for dinitrobenzenes (U.S. EPA, 1991a) assigned 1,4- dinitrobenzene to weight-of-evidence Group D, not classifiable as to human carcinogenicity, because of a lack of human and animal data and negative results for genotoxicity in bacteria. 1,4-Dinitrobenzene is not included on IRIS (U.S. EPA, 2006) or 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 (1,2-, 1,3- and 1,4- isomers) of dinitrobenzene, with a skin notation, to protect against anoxia resulting from methemoglobin formation. 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 (2001) REL-TWA for 1,4-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 1,4- dinitrobenzene; ATSDR (1995) published a toxicological profile on 1,3-dinitrobenzene, but this document has no information about 1,4-dinitrobenzene. IARC (2002) and the NTP (2002) have not evaluated the carcinogenicity of 1,4-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 1,4-dinitrobenzene. The following databases were searched: TOXLINE, MEDLINE, CANCERLIT, TOXLIT/BIOSIS, RTECS, HSDB, GENETOX, CCRIS, TSCATS, EMIC/EMICBACK and DART/ETICBACK. REVIEW OF PERTINENT DATA Human Studies No data were located regarding oral exposure of humans to 1,4-dinitrobenzene or subchronic or chronic inhalation exposure of humans to 1,4-dinitrobenzene at known levels. In general, occupational incidents involved combined inhalation and dermal exposure and exposure 3 ------- 06-16-2006 levels were not reported (ACGIH, 2001b). Cyanosis and methemoglobinemia were the major 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 1,4-dinitrobenzene in animals following chronic or subchronic oral or inhalation exposure. Analogy to 1,3-Dinitrobenzene Data on physical properties, pharmacokinetics and acute effects suggest that toxicity from chronic oral exposure to 1,4-dinitrobenzene will be similar to that of 1,3-dinitrobenzene. The physical properties of the two isomers are generally similar, except that the 1,4-isomer is considerably less soluble in water and has a higher melting point (Table 1). Table 1. Selected Properties of Dinitrobenzenes (U.S. EPA, 1985,1991a; O'Neil et al., 2001) Physical and Chemical Property 1,4-Dinitrobenzene 1,3-Dinitrobenzene Physical state white crystalline solid yellow crystalline solid Melting point °C 172-173 89.9 Boiling point °C 299 (at 777 mm Hg) 291 (at 756 mm Hg) Specific gravity 1.6 1.546 Vapor pressure (mm Hg) 2.11 x 10"4 2.23 x 10"4 Water solubility (mg/L) 80 at 20°C 370 at 20°C Log octanol/water partition coefficient 1.46 1.49 Pharmacokinetic data suggest a similar fate for all three dinitrobenzenes in mammalian systems (U.S. EPA, 1991a). Gavage studies 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 l,3-dinitro-[14C]-benzene, absorption of 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 91.3% for 1,4- dinitrobenzene, 82.6% for 1,3-dinitrobenzene and 92.4% for 1,2-dinitrobenzene. Radioactivity 4 ------- 06-16-2006 in urine accounted for 75.1, 63.2 and 81.3% of the dose, and in feces, 8.7, 17.4 and 7.6% of the dose for 1,4-, 1,3- and 1,2-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 1,3-dinitrobenzene were 3-aminoacetanilide (22%), 4-acetamidophenyl sulfate (6%), 1,3-diacetamidobenzene (7%) and 3-nitroanilinc-A''-glucuronidc. The major urinary metabolites of 1,2-dinitrobenzene were 5*-(2-nitrophenyl)-A^-acetylcysteine (42%), 2-nitroaniline- /Y-glucuronide (4%), 2-amino-3-nitrophenyl sulfate (1.5%) and 2-(A,'-hydroxylaminc)- nitrobenzene (1-2%). The major urinary metabolites of 1,4-dinitrobenzene were 2-amino-5- nitrophenyl sulfate (35%), 5*-(4-nitrophenyl)-A^-acetylcysteine (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, 6% of added 1,4-dinitrobenzene was conjugated to glutathione, 10% was reduced to 4-nitrophenylhydroxylamine and 40% was covalently bound to erythrocyte macromolecules. In erythrocytes treated with 1,3-dinitrobenzene, no metabolites were detected, but 2% was covalently bound to macromolecules. In erythrocytes treated with 1,2-dinitrobenzene, 37% was conjugated to glutathione and 24% was conjugated to 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 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 dinitrobenzenes causes methemoglobin formation in humans and animals (U.S. EPA, 1985, 1991a). In an acute occupational incident, five steampress operators exposed to an adhesive containing 1% 1,4-dinitrotoluene as a contaminant developed blood methemoglobin levels as high as 41.2% and symptoms including cyanosis, headache, nausea, chest pain, dizziness and confusion (U.S. EPA, 1991a; Benya and Cornish, 1994). One worker had a seizure. In a simulation later conducted by OSHA, the blood methemoglobin level of the steampress operator rose to 12.5% after 2 hours. The incident involved combined inhalation and dermal exposure. An acute oral LD0 of 28 mg/kg has been reported for 1,3-dinitrobenzene in humans (U.S. EPA, 1991a). The acute oral LD0 in rats was 29 mg/kg for 1,4-dinitrobenzene and 27 mg/kg for 1,3-dinitrobenzene (U.S. EPA, 1991a). The acute oral LD0s in rats were 250, 27 5 ------- 06-16-2006 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, and neither compound required metabolic activation for its effect (French et al., 1995); 1,3-dinitrobenzene was not effective on 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. There is some in vitro evidence for genotoxicity of 1,4- and 1,3-dinitrobenzene (U.S. EPA, 1985, 1991a). With or without metabolic activation, 1,4- and 1,3-dinitrobenzene did not induce reverse mutations in Salmonella typhimurium strains TA100NR (nitroreductase-deficient) or TA1537. 1,3-Dinitrobenzene yielded positive results in strains TA98 and TA1538, and conflicting, but usually positive, results in TA100 and TA1535, whereas 1,4-dinitrobenzene gave conflicting results in all of these strains and only tested positively at higher concentrations (U.S. EPA, 1985, 1991a). Neither 1,4- nor 1,3-dinitrobenzene induced unscheduled DNA synthesis in cultured rat hepatocytes (U.S. EPA, 1991a). 1,4-Dinitrobenzene, as well as the 1,2- and 1,3- 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 1,4-DINITROBENZENE BY ANALOGY TO 1,3-DINITROBENZENE No data are available for the chronic or subchronic oral toxicity of 1,4-dinitrobenzene in humans or animals. However, a chronic RfD of 1E-4 mg/kg-day is available for 1,3- dinitrobenzene on IRIS (U.S. EPA, 2006) and a related subchronic RfD1 of 1E-3 is available for 'The HEAST (1997) misstates the uncertainty factor for the subchronic RfD for 1,3-dinitrobenzene; it was 300 and not 100. 6 ------- 06-16-2006 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 1,4-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 properties of 1,4- and 1,3-dinitrobenzene are similar and both isomers have the ability to convert hemoglobin to methemoglobin. Although there are differences in pharmacokinetic pathways, the major hepatic metabolites (nitroanilines) of both compounds are also methemoglobin-producing. The similar acute toxicity of 1,4- and 1,3-dinitrobenzene suggests that p-RfDs based on 1,3-dinitrobenzene will be sufficiently protective for exposures to 1.4-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 1,4-dinitrobenzene. The subchronic RfD for 1,4-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 1,4-dinitrobenzene. These 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 p-RfDs for 1,4-dinitrobenzene is low, as no relevant studies were located and the RfDs were derived by analogy to the 1,3-dinitrobenzene isomer. DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC INHALATION RfC VALUES FOR 1,4-DINITROBENZENE No data are available for the chronic or subchronic inhalation toxicity of 1,4- dinitrobenzene in humans or animals. In addition, no information is available for the other isomers of 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 1,4-dinitrobenzene. DERIVATION OF A PROVISIONAL CARCINOGENICITY ASSESSMENT FOR 1,4-DINITROBENZENE No human or animal carcinogenicity data were located for 1,4-dinitrobenzene. In vitro genotoxicity data indicate that the compound is sometimes mutagenic in bacteria and that it may induce chromosomal aberration in human lymphocytes. Under the U.S. EPA (2005) cancer guidelines, the available data are inadequate for an assessment of human carcinogenic potential. 7 ------- 06-16-2006 Derivation of quantitative estimates of cancer risk for 1,4-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. p. 29. 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. 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, http://www.atsdr.cdc.gov/gsql/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. Cody, T.E., S. Witherup, L. Hastings et al. 1981. 1,3-Dinitrobenzene: Toxic effect 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. Relationships 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 IARC agents and summary evaluations. Online, http://monographs.iarc.fr/ 8 ------- 06-16-2006 NIOSH (National Institute for Occupational Safety and Health). 2001. p-Dinitrobenzene. CASRN 100-25-4. NIOSH Pocket Guide to Chemical Hazards. Online. http://www.cdc.gov/niosh/npg/npgd0233.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, p. 3299. 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-). Preared 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. 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. 9 ------- 06-16-2006 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 10 ------- |