United States
Environmental Protection
1=1 m m Agency
EPA/690/R-11/066F
Final
7-19-2011
Provisional Peer-Reviewed Toxicity Values for
Tris(3 -chloro-1 -propyl)phosphate
CASRN 1067-98-7
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
Alan Weinrich, 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	iii
BACKGROUND	4
DISCLAIMERS	4
QUESTIONS REGARDING PPRTVS	4
INTRODUCTION	5
REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER)	7
DERIVATION 01 PROVISIONAL VALUES	7
CANCER WOE DESCRIPTOR	7
MODE-OF-ACTION (MOA) DISCUSSION	7
REFERENCES	7
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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
TRIS(3-CHLORO-l-PROPYL)PHOSPHATE (CASRN 1067-98-7)
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).
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INTRODUCTION
Tris(3-chloro-l-propyl)phosphate, CAS No. 1067-98-7, belongs to the class of
compounds known as chlorinated alkyl phosphate esters (NRC, 2000). Chemicals in this class
generally are used as flame retardants and plasticizers. Tris(l-chloro-2-propyl) phosphate
(TCPP), CAS No. 13674-84-5, is an isomer of this compound (NRC, 2000); its toxicology is
under review by the Agency for Toxic Substances and Disease Registry (ASTDR, 2009),
whereas tris(3-chloro-l-propyl)phosphate has not been reviewed. Figure 1 shows the chemical
structure of tris(3-chloro-l-propyl)phosphate, and Table 1 lists the physicochemical properties of
both tris(3-chloro-l-propyl)phosphate and TCPP.
el
Figure 1. Tris(3-chloro-l-propyl)phosphate Structure
Table 1. Physicochemical Properties for Tris(3-chloro-l-propyl)phosphate and TCPP3
Property (unit)
Estimated Value for
Tris(3-chloro-l-
propyl)phosphateb
Value for
Tris(l-Chloro-2-Propyl) Phosphate
Boiling point (C)
Not available
235-248
Melting point (C)
84
380
Density (g/cm )
Not available
1.29
Vapor pressure (Pa at 25C)
0.0006
<266.6
pH
Not available
Not available
Solubility in water (g/100 mL at
25C)
0.0019
0.11-0.12
Relative vapor density (air =1)
Not available
Not available
Molecular weight (g/mol)
327.57
327.59
aData specific to tris(3-chloro-l-propyl)phosphate often were not available; however, the physicochemical properties
of TCPP are presented when available (NRC, 2000).
bEstimated values from Episuite software using PBT Profiler (www.pbtprofiler.net).
http://lb.chemie.uni-hamburg.de/static/RN/l_1016-82-6%20.. ,%201070-89-9. php?content= 120/hxaHikLm.
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No reference dose (RfD), reference concentration (RfC), or cancer assessment for
tris(3-chloro-l-propyl)phosphate is included in the IRIS database (U.S. EPA, 201 la) or on the
Drinking Water Standards and Health Advisories List (U.S. EPA, 2009). The HEAST does not
report RfD or RfC values (U.S. EPA, 201 lb). The Chemical Assessments and Related Activities
(CARA) list (U.S. EPA, 1994) does not include a Health and Environmental Effects Profile
(HEEP) for tris(3-chloro-l-propyl)phosphate. The toxicity of tris(3-chloro-l-propyl)phosphate
has not been reviewed by ATSDR (2011) or the World Health Organization (WHO, 2011).
ATSDR (2009) has reviewed the toxicity of several phosphate ester flame retardants but not
tris(3-chloro-l-propyl)phosphate. The California Environmental Protection Agency (CalEPA,
2008, 2009) has not derived toxicity values for exposure to tris(3-chloro-l-propyl)phosphate. No
occupational exposure limits for tris(3-chloro-l-propyl)phosphate have been derived by the
American Conference of Governmental Industrial Hygienists (ACGIH, 2011), the National
Institute of Occupational Safety and Health (NIOSH, 2010), or the Occupational Safety and
Health Administration (OSHA, 2010).
The HEAST (U.S. EPA, 201 lb) does not report any cancer weight-of-evidence (WOE) or
oral slope factor values for tris(3-chloro-l-propyl)phosphate. The International Agency for
Research on Cancer (IARC, 2011) has not reviewed the carcinogenic potential of tris(3-chloro-
1-propyl)phosphate. Tris(3-chloro-l-propyl)phosphate is not included in the 11th Report on
Carcinogens (NTP, 2005). CalEPA (2008) has not prepared a quantitative estimate of
carcinogenic potential for tris(3-chloro-l-propyl)phosphate.
Literature searches were conducted on sources published from 1900 through
March 8, 2011 for studies relevant to the derivation of provisional toxicity values for
tris(3-chloro-l-propyl)phosphate, CAS No. 1067-98-7. 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.
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REVIEW OF POTENTIALLY RELEVANT DATA
(CANCER AND NONCANCER)
The literature search revealed no human or animal studies (acute-, short-term-, or chronic
duration), for tris(3-chloro-l-propyl)phosphate. Neither the NICNAS (2001) review of the
trisphosphates nor the NAS (2000) or ATSDR (2009) reviews of flame-retardant chemicals
included relevant information on tris-3-chloropropylphosphate. Nakamura et al. (1979) found
that tris(3-chloro-l-propyl)phosphate generally was not mutagenic when tested against
Salmonella typhimurium TA98, TA100, TA1535, TA1537, or TA1538, with and without rat
liver in vitro metabolic activation. Because the database for tris-3-chloropropylphosphate does
not include even an LD50, there are insufficient data to indicate whether the toxicology of
tris-3-chloropropylphosphate is similar to that for tris(l-chloro-2-propyl) phosphate or other
isomers.
DERIVATION OF PROVISIONAL VALUES
Limitations in the available data preclude development of cancer or noncancer toxicity
values.
CANCER WOE DESCRIPTOR
Limitations in the available data preclude development of a WOE descriptor.
MODE-OF-ACTION (MOA) DISCUSSION
Limitations in the available data preclude determination of a MOA discussion.
REFERENCES
ACGIH (American Conference of Governmental Industrial Hygienists). (2011) Threshold limit
values for chemical substances and physical agents and biological exposure indices. ACGIH,
Cincinnati, OH. Available online by subscription at http://www.acgih.org/ChemSearch/
index.cfm. Accessed on June 15, 2011.
ATSDR (Agency for Toxic Substances and Disease Registry). (2009) Draft Toxicological
profile for Phosphate ester flame retardants. U.S. Department of Health and Human Services,
Public Health Service, Atlanta, GA. Available online at http://www.atsdr.cdc.gov/toxprofiles/
tp202.pdf. Accessed on March 9, 2011.
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ATSDR (Agency for Toxic Substances and Disease Registry). (2011) 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
March 8, 2011.
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/
allrels.html. Accessed on March 8, 2011.
CalEPA (California Environmental Protection Agency). (2009) OEHHA toxicity criteria
database. Office of Environmental Health Hazard Assessment, Sacramento, CA. Available
online at http://www.oehha.ca.gov/riskAChemicalDB/index.asp. Accessed on March 8, 2011.
IARC (International Agency for Research on Cancer). (2011) 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 March 8, 2011.
Nakamura A; Tateno N; Kojima S; Kaniwa Ma; Kawamura T. (1979) Mutagenicity of
halogenated alkanols and their phosphoric acid esters for Salmonella typhimurium. Mutat Res
66:373-380.
NAS (National Academy of Sciences). (2000) Toxicological risks of selected flame-retardant
chemicals. Washington, DC: The National Academies Press. Available online at
http://download.nap.edu/cart/deliver.cgi?record_id=9841&type=pdf_chapter&free=l. Accessed
on March 9, 2011.
NICNAS (National Industrial Chemicals Notification and Assessment Scheme). (2001)
Trisphosphates. Priority existing chemical report no. 17. Commonwealth of Australia, Sydney,
Australia. Available online at http://www.nicnas.gov.au/publications/car/pec/PEC17/PEC_17_
Full_Report_PDF.pdf. Accessed March 9, 2011.
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
March 8, 2011.
NRC (National Research Council) 2000 Toxicological risks of selected flame-retardant
Chemicals. Subcommittee on Flame-Retardant Chemicals, Committee on Toxicology, Board on
Environmental Studies and Toxicology, Commission on Life Sciences. Available online at
http://www.nap.edu/catalog/9841.html. Accessed on March 9, 2011.
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-server.mehs.nih.gov/index.cfm?objectid=
32BA9724-F1F6-975E-7FCE50709CB4C932. Accessed on March 8, 2011.
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OSHA (Occupational Safety and Health Administration). (2011) 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=10286. Accessed on March 10, 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=
60001G8L.txt.
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://deq.state.wy.us/wqd/groundwater/downloads/dwstandards2009%
5Bl%5D.pdf. Accessed March 8, 2011.
U.S. EPA (Environmental Protection Agency). (201 la) Integrated risk information system
(IRIS). Office of Research and Development, National Center for Environmental Assessment,
Washington, DC. Available online at http://www.epa.gov/iris/. Accessed March 8, 2011.
U.S. EPA (Environmental Protection Agency). (201 lb) 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 March 8, 2011.
WHO (World Health Organization). (2011) Online catalogs for the Environmental Health
Criteria series. Available online at http://www.who.int/topics/environmental_health/en/.
Accessed March 8, 2011.
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