iPs	United States
Environmental Protection
m»Agency
EPA/690/R-11/004F
Final
6-1-2011
Provisional Peer-Reviewed Toxicity Values for
3 -Amino-4-chlorobenzotrifluoride
(CASRN 121-50-6)
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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AUTHORS, CONTRIBUTORS, AND REVIEWERS
CHEMICAL MANAGER
Custodio V. Muianga, PhD, M.P.H.
CONTRIBUTOR
Jon Reid, 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).

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TABLE OF CONTENTS
COMMONLY USED ABBREVIATIONS	ii
BACKGROUND	1
DISCLAIMERS	1
QUESTIONS REGARDING PPRTVS	 1
INTRODUCTION	2
REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER)	4
DERIVATION 01 PROVISIONAL VALUES	4
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR	4
MODE-OF-ACTION (MOA) DISCI SSION	5
REFERENCES	5
i	3-Amino-4-chlorobenzotrifluoride

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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
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PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR
3-AMINO-4-CHLOROBENZOTRIFLUORIDE (CASRN 121-50-6)
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 flittp://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).
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INTRODUCTION
3-Amino-4-chlorobenzotrifluoride [synonyms: 2-chloro-5-trifluoromethylaniline;
2-chloro-5-trifluoromethyl-phenylamine; 2-chloro-5-(trifluoromethyl)aniline; 2-chloro-
5-(trifluoromethyl)phenylamine; benzenamine, 2-chloro-5-(trifluoromethyl)] CASRN 121-50-6
is a clear liquid, colorless to light yellow, with a penetrating odor, synthetically produced and
used in the chemical industry. It is stable under normal temperatures and pressures. 3-Amino-
4-chlorobenzotrifluoride presents a solubility of 11 g/L at 60°C in water and is soluble in most of
organic solvents. The decomposition products of this chemical includes hydrogen chloride,
nitrogen oxides, carbon monoxide, carbon dioxide, and hydrogen fluoride gas (Merck KGaA,
2010; ChemExper, 2011). The molecular formula for 3-amino-4-chlorobenzofluoride is
C7H5CIF3N (see Figure 1 for the structure). A table of chemico-physical properties is provided
below (see Table 1).
F
nh2
Figure 1. 3-Amino-4-chlorobenzotrifluoride Structure
Table 1. Physicochemical Properties
(3-Amino-4-chlorobenzotrifluoride CASRN 121-50-6)3
Property (unit)
Value
Boiling point (°C)
82-83 (9 mmHg)
Melting point (°C)
10
Density (g/cm )
1.428 @20°C
Vapor pressure (mbar)
0.15
pH (unitless)
-
Solubility in water (g/L at 60°C)
11
Molecular weight (g/mol)
195.57
aSources: Merck KGaA (2010), ChemExper (2011)
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No Reference Dose (RfD), Reference Concentration (RfC), or cancer assessment for
3-amino-4-chlorobenzotrifluoride	is included in the IRIS database (U.S. EPA, 2010) or on the
Drinking Water Standards and Health Advisories List (U.S. EPA, 2009). No RfD or RfC values
are reported in the Health Effects Assessment Summary Tables (HEAST; US. EPA, 2003). The
Chemical Assessments and Related Activities (CARA) list (U.S. EPA, 1994) does not include a
Health and Environmental Effects Profile (HEEP) for 3-amino-4-chlorobenzotrifluoride
(U.S. EPA, 1985). The toxicity of 3-amino-4-chlorobenzotrifluoride 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 3-amino-4-chlorobenzotrifluoride. The
American Conference of Governmental Industrial Hygienists (ACGIH, 2010) has not derived
threshold limit value (TLV), nor biological exposure index; National Institute of Occupational
Safety and Health (NIOSH, 2010) has cited neither a recommended occupational limit (REL),
and Occupational Safety and Health Administration (OSHA, 2006b) has not cited permissible
exposure limit (PEL) for 3-amino-4-chlorobenzotrifluoride. However, OSHA (2006a) does cite a
PEL 8-hour time-weighted average (TWA) of 2.5 mg/m3 (3 ppm) for fluorides (as F), which is
similar to the OSHA PEL for HF (as F) of 2.5 mg/m3 (3 ppm). NIOSH (2010) reports presents a
REL of 2.5 mg/m3 (3 ppm) for HF, and ACGIH (2008) presents a TLV-TWA of 2.5 mg/m3 for
fluorides, as F and TLV-TWA of 0.5 ppm, a ceiling limit of 2 ppm (skin) for HF.
The HEAST (U.S. EPA, 2003) does not report any values based on the U.S. EPA (1986)
cancer weight-of-evidence classification for 3-amino-4-chlorobenzotrifluoride. 3-Amino-
4-chlorobenzotrifluoride	has not been evaluated under the 2005 Guidelines for Carcinogen Risk
Assessment (U.S. EPA, 2005). The International Agency for Research on Cancer (IARC, 2010)
has not reviewed the carcinogenic potential of 3-amino-4-chlorobenzotrifluoride. 3-Amino-
4-chlorobenzotrifluoride is not included in the 11th Report on Carcinogens (NTP, 2005).
CalEPA (2008) has not prepared a quantitative estimate of carcinogenic potential for 3-amino-
4-chlorobenzotri fluoride.
Literature searches were conducted on sources published from 1900 through May 2011
for studies relevant to the derivation of provisional toxicity values for 3-amino-
4-chlorobenzotrifluoride, CAS No. 121-50-6. 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
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Worldwide Science. The following databases outside of HERO were searched for risk
assessment values: ACGM, AT SDR, 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 (i.e., acute-, short-term-,
subchronic-, or chronic-duration) for 3-Amino-4chlorobenzotrifluoride.
Doull et al. (1962) reported results of preliminary toxicity studies of 1200 compounds
that included 3-amino-4-benzotrifluoride. The toxicity studies were necessary to determine the
amount of each compound the mice could receive before the chemical toxicity caused death.
Small group of mice were injected intraperitoneally with increasing dosage levels of each
compound, and the resulting mortality was recorded for one week. The approximate LD50 (lethal
dose, 50%; 7-day) for 3-amino-4-benzotrifluoride was 100 mg/kg. No additional information
was reported.
The Merck Safety Data Sheet (Merck KGaA, 2010) reported an //-octanol/water partition
coefficient log Pow of 3.19 for 3-amino-4-chlorobenzotrifluoride, which indicate a remarkable
bioaccumulation potential. Also reported is an LC50 (lethal concentration, 50%) of 7 mg/L for
zebra fish (Danio rerio) for an exposure time of 96 hours and an EC50 (Half maximal effective
concentration 50) of 62 mg/L for bacteria for an exposure time of 3 hours (Merck KGaA, 2010).
Another study by Dacarro et al. (1986), examined the toxicity of eight compounds (e.g.,
derivatives of benzotrifluoride and intermediates in the production of several herbicides) by a
test based on the inhibition of the cell multiplication of pseudomonas putida that included
3-amino-4-chlorobenzotrifluoride. Through a mathematical model analogous to that proposed
by Weiball, an EC50 of over 100 mg/L was estimated (Dacarro et al., 1986).
DERIVATION OF PROVISIONAL VALUES
Limitations in the available data preclude development of cancer and noncancer toxicity
values for 3-amino-4-chlorobenzotrifluoride.
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR
Limitations in the available data preclude development of a WOE descriptor.
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MODE-OF-ACTION (MOA) DISCUSSION
Limitations in the available data preclude determination of a MOA discussion.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). (2008) Threshold limit
values for chemical substances and physical agents and biological exposure indices. Cincinnati,
OH: ACGIH. As cited in HSDB (Hazardous Substances Data Bank). Available online at
http://toxnet.nlm.nih.eov/cgi-bin/sis/htmlgen7HSDB. Accessed on October 4, 2010.
ACGIH (American Conference of Governmental Industrial Hygienists). (2010) Threshold limit
values for chemical substances and physical agents and biological exposure indices. Cincinnati,
OH: ACGIH. As cited in HSDB (Hazardous Substances Data Bank). Available online at
http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB. Accessed on October 4, 2010.
ATSDR (Agency for Toxic Substances and Disease Registry). (2010) Toxicological profile
information sheet. U.S. Department of Health and Human Services, Public Health Service.
Available online at http://www.atsdr.cdc.gov/toxprofiles/index.asp. Accessed on October 4,
2010.
CalEPA (California Environmental Protection Agency). (2008) All OEHHA acute, 8-hour and
chronic reference exposure levels (chRELs) as of December 18, 2008. Office of Environmental
Health Hazard Assessment, Sacramento, CA. Available online at
http://www.oehha.ca.gov/air/chronic rets/AllChrels.html. October 4, 2010.
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 October 4, 2010.
ChemExper. 2011. Chemical directory. Available online at http://www.chemexper.com/.
Dacarro, C; Baldi, M; Bonferoni, MC; Riganti, V. (1986) Test di inibizone della
moltiplicatiozione cellular di pseudomonas putida: Curve di Weibull dose-effect di derivati del
benzotrifluoruro. L'Igiene Moderna 86:223-239.
Doull, J; Plzak, V; Brois, S. (1962) A Survey of compounds for radiation protection. School of
Aerospace Medicine, USAF Aerospace Medical Division (ASFC), Brooks Air Force Base,
Texas. 62-29. Available online at http://www.dtic.mil/cgi-
bin/GetTRDoc?AD A D277689& Location L'2&doc GetTRDoc.pdt'.
IARC (International Agency for Research on Cancer). (2010) IARC Monographs on the
evaluation of carcinogenic risks to humans. Lyon, France: IARC. Available online at
http://monographs.iarc.fr/ENG/Monographs/PDFs/index.pdf. Accessed on October 4, 2010.
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Merck KGaA. (2010) Safety data sheet. 841772 3-Amino-4-chlorobenzotrifluoride. ©Merck
KGaA, Darmstaadt, Germany.
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
October 4, 2010.
NTP (National Toxicology Program). (2005) 11th Report on carcinogens. U.S. Department of
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32BA9724-F1F6-975E-7FCE50709CB4C932. Accessed on October 4, 2010.
OSHA (Occupational Safety and Health Administration). (2006a) Table Z-l limits for air
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substances. U.S. Department of Labor, Washington, DC; OSHA Standard 1910.1000. Available
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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.
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