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 ------- 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). l Tris(3 -chloro-1 -propyl )phosphate ------- 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 li Tris(3 -chloro-1 -propyl )phosphate ------- 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 7-19-2011 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). 4 Tris(3 -chloro-1 -propyl )phosphate ------- FINAL 7-19-2011 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 25°C) 0.0006 <266.6 pH Not available Not available Solubility in water (g/100 mL at 25°C) 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. 5 Tris(3 -chloro-1 -propyl )phosphate ------- FINAL 7-19-2011 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. 6 Tris(3 -chloro-1 -propyl )phosphate ------- FINAL 7-19-2011 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. 7 Tris(3 -chloro-1 -propyl )phosphate ------- FINAL 7-19-2011 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. 8 Tris(3 -chloro-1 -propyl )phosphate ------- FINAL 7-19-2011 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. 9 Tris(3 -chloro-1 -propyl )phosphate ------- |