United States
Environmental Protection
1=1 m m Agency
EPA/690/R-11/043F
Final
8-22-2011
Provisional Peer-Reviewed Toxicity Values for
2-Nitrodiphenylamine
(CASRN 119-75-5)
Superfund Health Risk Technical Support Center
National Center for Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati, OH 45268

-------
AUTHORS, CONTRIBUTORS, AND REVIEWERS
CHEMICAL MANAGER:
Jason C. Lambert, National Center for Environmental Assessment, Cincinnati, OH
DRAFT DOCUMENT PREPARED BY:
National Center for Environmental Assessment, Cincinnati, OH
This document was externally peer-reviewed under contract to:
Eastern Research Group, Inc.
110 Hartwell Avenue
Lexington, MA 02421-3136
Questions regarding the contents of this document may be directed to the U.S. EPA Office of
Research and Development's National Center for Environmental Assessment, Superfund Health
Risk Technical Support Center (513-569-7300).
l

-------
TABLE OF CONTENTS
COMMONLY USED ABBREVIATIONS	iii
BACKGROUND	1
DISCLAIMERS	1
QUESTIONS REGARDING PPRTVS	 1
INTRODUCTION	2
REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER)	3
DERIVATION 01 PROVISIONAL VALUES	4
CANCER WOE DESCRIPTOR	4
MODE-OF-ACTION DISCUSSION	4
REFERENCES	4
ii

-------
COMMONLY USED ABBREVIATIONS
BMC
benchmark concentration
BMD
benchmark dose
BMCL
benchmark concentration lower bound 95% confidence interval
BMDL
benchmark dose lower bound 95% confidence interval
HEC
human equivalent concentration
HED
human equivalent dose
IUR
inhalation unit risk
LOAEL
lowest-observed-adverse-effect level
LOAELadj
LOAEL adjusted to continuous exposure duration
LOAELhec
LOAEL adjusted for dosimetric differences across species to a human
NOAEL
no-ob served-adverse-effect level
NOAELadj
NOAEL adjusted to continuous exposure duration
NOAELhec
NOAEL adjusted for dosimetric differences across species to a human
NOEL
no-ob served-effect level
OSF
oral slope factor
p-IUR
provisional inhalation unit risk
p-OSF
provisional oral slope factor
p-RfC
provisional reference concentration (inhalation)
p-RfD
provisional reference dose (oral)
POD
point of departure
RfC
reference concentration (inhalation)
RfD
reference dose (oral)
UF
uncertainty factor
UFa
animal-to-human uncertainty factor
UFC
composite uncertainty factor
UFd
incomplete-to-complete database uncertainty factor
UFh
interhuman uncertainty factor
UFl
LOAEL-to-NOAEL uncertainty factor
UFS
subchronic-to-chronic uncertainty factor
WOE
weight of evidence
11

-------
FINAL
8-22-2011
PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR
2-NITRODIPEHNYLAMINE (CASRN 119-75-5)
BACKGROUND
A Provisional Peer-Reviewed Toxicity Value (PPRTV) is defined as a toxicity value
derived for use in the Superfund Program. PPRTVs are derived after a review of the relevant
scientific literature using established Agency guidance on human health toxicity value
derivations. All PPRTV assessments receive internal review by a standing panel of National
Center for Environment Assessment (NCEA) scientists and an independent external peer review
by three scientific experts.
The purpose of this document is to provide support for the hazard and dose-response
assessment pertaining to chronic and subchronic exposures to substances of concern, to present
the major conclusions reached in the hazard identification and derivation of the PPRTVs, and to
characterize the overall confidence in these conclusions and toxicity values. It is not intended to
be a comprehensive treatise on the chemical or toxicological nature of this substance.
The PPRTV review process provides needed toxicity values in a quick turnaround
timeframe while maintaining scientific quality. PPRTV assessments are updated approximately
on a 5-year cycle for new data or methodologies that might impact the toxicity values or
characterization of potential for adverse human health effects and are revised as appropriate. It is
important to utilize the PPRTV database (http://hhpprtv.ornl.gov) to obtain the current
information available. When a final Integrated Risk Information System (IRIS) assessment is
made publicly available on the Internet (www.epa.gov/iris), the respective PPRTVs are removed
from the database.
DISCLAIMERS
The PPRTV document provides toxicity values and information about the adverse effects
of the chemical and the evidence on which the value is based, including the strengths and
limitations of the data. All users are advised to review the information provided in this
document to ensure that the PPRTV used is appropriate for the types of exposures and
circumstances at the site in question and the risk management decision that would be supported
by the risk assessment.
Other U.S. Environmental Protection Agency (EPA) programs or external parties who
may choose to use PPRTVs are advised that Superfund resources will not generally be used to
respond to challenges, if any, of PPRTVs used in a context outside of the Superfund program.
QUESTIONS REGARDING PPRTVS
Questions regarding the contents and appropriate use of this PPRTV assessment should
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).
1
2-Nitrodiphenyl amine

-------
FINAL
8-22-2011
INTRODUCTION
2-Nitrodiphenylamine, CAS No. 119-75-5, is a solid, nitroaromatic compound used in the
manufacture of fuel, propellants, and explosives (ATSDR, 1995). It is also used as a solvent
dye. Although the human and animal health effects are unknown, 2-nitrodiphenylamine has
been shown to enter the bloodstream via oral consumption of water or food. The distribution of
2-nitrodiphenylamine following inhalation or dermal exposure has not been examined. Figure 1
shows the chemical structure of 2-nitrodiphenylamine, and Table 1 presents the physicochemical
properties of 2-nitrodiphenylamine.
Ck + o
Figure 1. 2-Nitrodiphenylamine Structure (CASRN 119-75-5)
Table 1. Physicochemical Properties for 2-Nitrodiphenylamine (CASRN 119-75-5)
Property (unit)
Value
Boiling point (°C at 760 mmHg)
346b
Melting point (°C)
75a
Density (g/cm )
1.36b
Vapor pressure (kPa at 20°C)
Not available
pH (unitless)
5.0-7.0°
Solubility in water (mg/L at 25°C)
27.7d
Relative vapor density (air =1)
Not available
Molecular weight (g/mol)
214.223a
Flash point (°C)
Not available
Octanol/water partition coefficient (log K0Vi unitless)
3.66a
aU.S. National Library of Medicine (2010); experimental data.
bChemCAS (2010).
°Chemicalland21 (2010).
dU.S. National Library of Medicine (2010); estimated data.
No Reference Dose (RfD), Reference Concentration (RfC), or cancer assessment for
2-nitrodiphenylamine is included in the IRIS database (U.S. EPA, 2010a) or on the Drinking
Water Standards and Health Advisories List (U.S. EPA, 2009). No RfD or RfC values are
2
2-Nitrodiphenylamine

-------
FINAL
8-22-2011
reported in the Health Effects Assessment Summary Tables (HEAST) (U.S. EPA, 2010b). The
Chemical Assessments and Related Activities (CARA) list does not include a Health and
Environmental Effects Profile (HEEP) for 2-nitrodiphenylamine (U.S. EPA, 1994). The toxicity
of 2-nitrodiphenylamine has not been reviewed by the Agency for Toxic Substances and Disease
Registry (ATSDR, 2010) or the World Health Organization (WHO, 2010). The California
Environmental Protection Agency (CalEPA, 2008, 2009) has not derived toxicity values for
exposure to 2-nitrodiphenylamine. No occupational exposure limits for 2-nitrodiphenylamine
have been derived by the American Conference of Governmental Industrial Hygienists
(ACGIH, 2010), the National Institute of Occupational Safety and Health (NIOSH, 2010), or the
Occupational Safety and Health Administration (OSHA, 2010).
The HEAST (U.S. EPA, 2010b) does not report an EPA (1986) cancer
weight-of-evidence (WOE) classification or an oral slope factor. The International Agency for
Research on Cancer (IARC, 2010) has not reviewed the carcinogenic potential of
2-nitrodiphenylamine. 2-Nitrodiphenylamine is not included in the 11th Report on Carcinogens
(NTP, 2005). CalEPA (2008) has not prepared a quantitative estimate of carcinogenic potential
for 2-nitrodiphenylamine.
Literature searches were conducted on sources published from 1900 through July 2011
for studies relevant to the derivation of provisional toxicity values for 2-nitrodiphenylamine,
CAS No. 119-75-5. Searches were conducted using EPA's Health and Environmental Research
Online (HERO) database of scientific literature. HERO searches the following databases:
AGRICOLA; American Chemical Society; BioOne; Cochrane Library; DOE: Energy
Information Administration, Information Bridge, and Energy Citations Database; EBSCO:
Academic Search Complete; GeoRef Preview; GPO: Government Printing Office;
Informaworld; IngentaConnect; J-STAGE: Japan Science & Technology; JSTOR: Mathematics
& Statistics and Life Sciences; NSCEP/NEPIS (EPA publications available through the National
Service Center for Environmental Publications [NSCEP] and National Environmental
Publications Internet Site [NEPIS] database); PubMed: MEDLINE and CANCERLIT databases;
SAGE; Science Direct; Scirus; Scitopia; SpringerLink; TOXNET (Toxicology Data Network):
ANEUPL, CCRIS, ChemlDplus, CIS, CRISP, DART, EMIC, EPIDEM, ETICBACK, FEDRIP,
GENE-TOX, HAPAB, HEEP, HMTC, HSDB, IRIS, ITER, LactMed, Multi-Database Search,
NIOSH, NTIS, PESTAB, PPBIB, RISKLINE, TRI; and TSCATS; Virtual Health Library; Web
of Science (searches Current Content database among others); World Health Organization; and
Worldwide Science. The following databases outside of HERO were searched for risk
assessment values: ACGIH, ATSDR, CalEPA, EPA IRIS, EPA HEAST, EPA HEEP, EPA OW,
EPA TSCATS/TSCATS2, NIOSH, NTP, OSHA, and RTECS.
REVIEW OF POTENTIALLY RELEVANT DATA
(CANCER AND NONCANCER)
The literature search revealed no human or animal studies, at any relevant exposure
duration, available for hazard or dose-response assessment. However, the ATSDR published a
Toxicological Profile for Otto Fuel II (ATSDR, 1995), of which 2-nitrodiphenylamine is a minor
component. In this profile, limited information on the toxicity of 2-Nitrodiphenyl amine alone
was included. Following an acute oral exposure to 2-nitrodiphenylamine, a LD50 value of
3
2-Nitrodiphenyl amine

-------
FINAL
8-22-2011
6150 mg/kg was identified in rats (This information was obtained from a Material Safety Data
Sheet on 2-nitrodiphenylamine [American Cyanamid, 1982], as cited in ATSDR, 1995).
However, because the original acute study was unavailable for review, this value could not be
verified by the ATSDR or the EPA. A U.S. Army review indicated that oral
2-nitrodiphenylamine exposure in rats at a dose of 3070 mg/kg resulted in an elevation of blood
methemoglobin levels of 9.45% (U.S. Army, 1979; this information was obtained by the
U.S. Army through personal communication with American Cyanamid). Because the actual
study was unavailable for review, this information could not be verified by the ATSDR or the
EPA. No other information pertaining to noncancer toxicity of 2-nitrodiphenylamine could be
located.
DERIVATION OF PROVISIONAL VALUES
The lack of relevant data precludes development of both cancer and noncancer toxicity
values.
CANCER WOE DESCRIPTOR
The lack of data precludes development of a WOE descriptor.
MODE-OF-ACTION DISCUSSION
The lack of data precludes development of a mode-of-action discussion.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). (2010) Threshold limit
values for chemical substances and physical agents and biological exposure indices. Cincinnati,
OH. As cited in HSDB (Hazardous Substances Data Bank). Available online at
http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB. Accessed on November 09, 2010.
625688.
American Cyanamid. (1982) Material safety data sheet on 2-nitrodiphenylamine. American
Cyanamid Company, Wayne, NJ; MSDS no. 0404-01. As cited in ATSDR, 1995.
ATSDR (Agency for Toxic Substances and Disease Registry). (1995) Toxicological profile for
Otto Fuel II and its components. U.S. Department of Health and Human Services, Public Health
Service, Atlanta, GA. Available at http://www.atsdr.cdc.gov/toxprofiles/tp77.pdf. Accessed on
November 9, 2010.
4
2-Nitrodiphenyl amine

-------
FINAL
8-22-2011
ATSDR (Agency for Toxic Substances and Disease Registry). (2010) Toxicological profile
information sheet. U.S. Department of Health and Human Services, Public Health Service,
Atlanta, GA. Available online at http://www.atsdr.cdc.gov/toxprofiles/index.asp. Accessed on
November 9, 2010. 595415.
CalEPA (California Environmental Protection Agency). (2008) All OEHHA acute, 8-hour and
chronic reference exposure levels (chRELs) as on December 18, 2008. Office of Environmental
Health Hazard Assessment, Sacramento, CA. Available online at
http://www.oehha.ca.gov/air/al 1 rels.htm 1. Accessed on November 9, 2010. 595416.
CalEPA (California Environmental Protection Agency). (2009) Office of Environmental Health
Hazard Assessment. OEHHA Toxicity Criteria Database. Available online at
http://www.oehha.ca.gov/riskAChemicalDB/index.asp. Accessed on November 9, 2010.
595417.
ChemCAS. (2010) MSDS for 2-Nitrodiphenylamine. Available online at:
http://www.chemcas.org/drug/analytical/cas/119-75-5.asp. Accessed on November 10, 2010.
Chemicalland21. (2010) 2-Nitrodiphenylamine. Available online at
http://chemicalland21.com/specialtychem/finechem/2-NITRODIPHENYLAMINE.htm.
Accessed on November 9, 2010.
IARC (International Agency for Research on Cancer). (2010) Monographs on the evaluation of
carcinogenic risks to humans. Lyon, France: IARC. Available online at
http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php. Accessed on November 9, 2010.
597416.
NIOSH (National Institute for Occupational Safety and Health). (2010) NIOSH Pocket Guide
to Chemical Hazards. Index of chemical abstracts service registry numbers (CAS No.). Center
for Disease Control and Prevention, U.S. Department of Health, Education and Welfare,
Atlanta, GA. Available online at http://www.cdc.gov/niosh/npg/npgdcas.html. Accessed on
November 9, 2010. 625692.
NTP (National Toxicology Program). (2005) 11th Report on carcinogens. U.S. Department of
Health and Human Services, Public Health Service, National Institutes of Health, Research
Triangle Park, NC. Available online at http://ntp.niehs.nih.gov/ntp/roc/tocl 1.html. Accessed on
November 9, 2010. 093207.
OSHA (Occupational Safety and Health Administration). (2010) Air contaminants:
occupational safety and health standards for shipyard employment, subpart Z, toxic and
hazardous substances. U.S. Department of Labor, Washington, DC; OSHA Standard 1915.1000.
Available online at
http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=102
86. Accessed on November 9, 2010. 625691.
U.S. EPA (Environmental Protection Agency). (1986) Guidelines for carcinogen risk
assessment. Risk Assessment Forum, Washington, DC; EPA/630/R-00/004. September 1986.
Available online at http://epa.gov/raf/publications/pdfs/CA%20GUIDELINES_1986.PDF. .
199530.
5
2-Nitrodiphenylamine

-------
FINAL
8-22-2011
U.S. EPA (Environmental Protection Agency). (1994) Chemical Assessments and Related
Activities (CARA). Office of Health and Environmental Assessment, Washington, DC;
EPA/600/R-94/904. Available online at
nepis.epa.gov/Exe/ZyPURL.cgi?Dockey=6000 lG8L.txt. December. 596444.
U.S. EPA (Environmental Protection Agency). (2009) 2009 Edition of the drinking water
standards and health advisories. Office of Water, Washington, DC; EPA 822/R-09/011.
Available online at http://www.epa.gov/waterscience/drinking/standards/dwstandards2009.pdf.
Accessed November 9, 2010. 644141.
U.S. EPA (Environmental Protection Agency). (2010a) Integrated risk information system
(IRIS). Prepared by the Office of Research and Development, National Center for
Environmental Assessment, Washington, DC. Available online at http://www.epa.gov/iris.
Accessed November 9, 2010. 003752.
U.S. EPA (Environmental Protection Agency). (2010b) Health effects assessment summary
tables (HEAST). 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. Available online at http://epa-heast.ornl.gov. Accessed
November 9, 2010. 595422.
U.S. National Library of Medicine. (2010) ChemlDplus Lite: Physicial Properties, 2-nitro-
/V-phenyl-benzenamine, CAS RN: 119-75-5. Available online at
http://chem.sis.nlm.nih.gov/chemidplus/jsp/common/PhysicalProperties.jsp7calledFrommte.
Accessed on November 9, 2010.
WHO (World Health Organization). (2010) Online catalogs for the Environmental Health
Criteria series. Available online at http://www.who.int/ipcs/publications/ehc/en. Accessed
November 9, 2010. 595424.
6
2-Nitrodiphenyl amine

-------