United States
Environmental Protection
1=1 m m Agency
EPA/690/R-11/034F
Final
3-23-2011
Provisional Peer-Reviewed Toxicity Values for
?7-Methyl Dicyclohexylamine
(CASRN 7560-83-0)
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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AUTHORS, CONTRIBUTORS, AND REVIEWERS
CHEMICAL MANAGER
Scott C. Wesselkamper, PhD
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
HISTORY	1
DISCLAIMERS	1
QUESTIONS REGARDING PPRTVS	2
INTRODUCTION	2
REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NON-CANCER)	3
DERIVATION 01 PROVISIONAL VALUES	4
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR	4
MODE-OF-ACTION DISCI SSION	4
REFERENCES	4
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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
ft-METHYL DICYCLOHEXYLAMINE (CASRN 7560-83-0)
BACKGROUND
HISTORY
On December 5, 2003, the U.S. Environmental Protection Agency's (EPA) 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 (PPRTVs) 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 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 a
panel of six EPA scientists and external peer review by three independently selected scientific
experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the multiprogram
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 new information becomes available and scientific methods improve over time,
PPRTVs are reviewed on a 5-year basis and updated into the active database. 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 documents conclude that
a PPRTV cannot be derived based on inadequate data.
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 Resource Conservation and Recovery Act (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
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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 document 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.
INTRODUCTION
No reference dose (RfD), reference concentration (RfC), or cancer assessment for
//-methyl dicyclohexylamine is included in the IRIS database (U.S. EPA, 2010b) or on the
Drinking Water Standards and Health Advisories List (U.S. EPA, 2009). No RfD or RfC values
are reported in the HEAST (U.S. EPA, 2010a). The Chemical Assessments and Related
Activities (CARA) list (U.S. EPA, 1994) does not include a Health and Environmental Effects
Profile (HEEP) for //-methyl dicyclohexylamine. The toxicity of //-methyl dicyclohexylamine
has not been reviewed by the ATSDR (2010) or the World Health Organization (WHO, 2010).
CalEPA (2008, 2009a,b) has not derived toxicity values for exposure to //-methyl
dicyclohexylamine. No occupational exposure limits for //-methyl dicyclohexylamine have been
derived by the American Conference of Governmental Industrial Hygienists (ACGIH, 2010), the
National Institute of Occupational Safety and Health (NIOSH, 2005), or the Occupational Safety
and Health Administration (OSHA, 2010).
The HEAST (U.S. EPA, 2010a) does not report any values for «-methyl
dicyclohexylamine. //-Methyl dicyclohexylamine has not been evaluated under the 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
//-methyl dicyclohexylamine. //-Methyl dicyclohexylamine is not included in the 11th Report on
Carcinogens (NTP, 2005). CalEPA (2009c,d) has not prepared a quantitative estimate of
carcinogenic potential for //-methyl dicyclohexylamine.
Literature searches were conducted on sources published from 1900 through
October 8, 2010, for studies relevant to the derivation of provisional toxicity values for
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//-methyl dicyclohexylamine, CAS No. 7560-83-0. Searches were conducted using EPA's
Health and Environmental Research Online (HERO) evergreen 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 NON-CANCER)
The literature search revealed no usable human or animal studies (acute-, short term-,
subchronic-, or chronic-duration) for development of toxicity values for //-methyl
dicyclohexylamine. In an unpublished inhalation study by McGregor et al. (1981), dominant
lethal and cytogenetic tests were conducted in CD rats, and a sperm abnormality test was
conducted in B6C3Fi mice. Briefly, male and female CD rats and male B6C3Fi mice
(30/sex/group) were exposed to //-methyl dicyclohexylamine (98% purity) through whole-body
inhalation exposure at 0, 5, or 25 ppm (0, 40, or 200 mg/m3), 7 hours/day, for 5 consecutive
days. A single-exposure cytogenetic test was also conducted in male and female CD rats
(10/sex/group) employing 0, 5, or 20 ppm (0, 40, or 160 mg/m3) for 7 hours. There were no
signs of dominant lethal mutation inducing potential or anti-fertility effects in male rats, nor did
inhalation exposure to //-methyl dicyclohexylamine increase the frequency of aberrant cells in rat
bone marrow. Additionally, there were no effects upon the frequency of abnormal sperm in
mice. The study authors qualitatively reported that both mice and rats showed signs of severe
-3
systemic toxicity during exposure to 200 or 160 mg/m , including reduced response to auditory
stimuli, subdued behavior, nervous system effects (e.g., ataxia, convulsions), and mortality (in
mice). However, due to their qualitative nature, these study data cannot be used to develop
toxicity values.
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DERIVATION OF PROVISIONAL VALUES
Limitations in the available data preclude development of both cancer and noncancer
toxicity values for //-methyl dicyclohexylamine.
CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR
Limitations in the available data preclude development of a WOE descriptor.
MODE-OF-ACTION DISCUSSION
Limitations in the available data preclude determination 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,
Ohio. As cited in HSDB (Hazardous Substances Data Bank). Available online at
http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB. Accessed on 10/8/2010.
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 10/8/2010.
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/
allrels.html. Accessed on 10/8/2010.
CalEPA (California Environmental Protection Agency). (2009a) OEHHA/ARB approved
chronic reference exposure levels and target organs. Office of Environmental Health Hazard,
Sacramento, CA. Available online at http://www.arb.ca.gov/toxics/healthval/chronic.pdf.
Accessed on March 8, 2011.
CalEPA (California Environmental Protection Agency). (2009b) OEHHA toxicity criteria
database. Office of Environmental Health Hazard Assessment, Sacramento, CA. Available
online at http://www.oehha.ca.gOv/risk//ChemicalDB/index.asp. Accessed on 10/8/2010.
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CalEPA (California Environmental Protection Agency). (2009c) Hot spots unit risk and cancer
potency values. Office of Environmental Health Hazard Assessment, Sacramento, CA.
Available online at http://www.oehha.ca.gov/air/hot_spots/pdf/CPFs042909.pdf. Accessed on
10/8/2010.
CalEPA (California Environmental Protection Agency). (2009d) Hot spots unit risk and cancer
potency values. Appendix A. Office of Environmental Health Hazard Assessment, California,
CA. Available online at http://www.oehha.ca.gov/air/hot_spots/2009/AppendixA.pdf. Accessed
on 10/8/2010.
IARC (International Agency for Research on Cancer). (2010) IARC Monographs on the
evaluation of carcinogenic risks to humans. Available online at http://monographs.iarc.fr/ENG/
Monographs/PDFs/index.php. Accessed on 10/8/2010.
McGregor, DB. (1981). Tier II mutagenic screening of 13 NIOSH priority compounds.
Individual compound report «-methyl dicyclohexylamine, Report No. 36. National Institute for
Occupational Safety and Health (NIOSH), Cincinnati, OH. Available online at
http://www.ntis.gov/search/product.aspx?ABBR=PB83126607. Accessed on 2/18/2011.
NIOSH (National Institute for Occupational Safety and Health). (2005) NIOSH pocket guide to
chemical hazards. Centers for Disease Control and Prevention, Atlanta, GA. Index by CASRN.
Available online at http://www.cdc.gov/niosh/npg/npgdcas.html. Accessed on 10/8/2010.
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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
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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
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table=STANDARDS&p_id=10286. Accessed on 10/8/2010.
U.S. EPA (Environmental Protection Agency). (1986) Guidelines for carcinogen risk
assessment. Prepared by the Risk Assessment Forum, U.S. Environmental Protection Agency.
Washington, DC. Available online at http://www.epa.gov/raf/publications/pdfs/CA%20
GUIDELINE S_1986 PDF
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=
60001G8L.txt.
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U.S. EPA (Environmental Protection Agency). (2005) Guidelines for carcinogen risk
assessment. Risk Assessment Forum, Washington, DC; EPA/630/P-03/001F. Federal Register
70(66): 17765-17817. Available online at http://www.epa.gov/raf/publications/pdfs/
CANCER_GUIDELINES_FINAL_3 -25-05 PDF
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standards and health advisories. Office of Water, Washington, DC; EPA 822-R-06-013.
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Accessed on 10/8/2010.
U.S. EPA (Environmental Protection Agency). (2010a) Health effects assessment summary
tables (HEAST). Office of Research and Development, National Center for Environmental
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on 10/8/2010.
U.S. EPA (Environmental Protection Agency). (2010b) Integrated risk information system
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Washington, DC. Available online at http://www.epa.gov/iris/. Accessed on 10/8/2010.
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