United States Environmental Protection 1=1 m m Agency EPA/690/R-11/025F Final 5-19-2011 Provisional Peer-Reviewed Toxicity Values for n, ?7-Dimethy Icy clohexylamine (CASRN 98-94-2) 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: Harlal Choudhury, 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). ------- 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) 3 DERIVATION 01 PROVISIONAL VALUES 3 CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR 4 MODE-OF-ACTION (MOA) DISCI SSION 4 l ------- 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 5-19-2011 PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR «,«-DIMETHYLCYCLOHEXYLAMINE (CASRN 98-94-2) 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 //,//-Dim ethyl cyclohexyl amine ------- FINAL 5-19-2011 INTRODUCTION //.//-Dimethyl cycl ohexyl amine, CASRN 98-94-2, is an intermediate and catalyst used in the textile and rubber industry. The empirical formula for //,/7-dimethylcyclohexylamine is CgHi7N (see Figure 1). A table of physicochemical properties is provided below (see Table 1). Figure 1. «,«-Dimethylcyclohexylamine Structure Table 1. Physicochemical Properties Table («,«-Dimethylcyclohexylamine CASRN 98-94-2)a Property (unit) Value Boiling point (°C) 162-165 Melting point (°C) -60 Relative Density (water =1) 0.85 Vapor pressure (kPa at 25°C) 0.4 pH (unitless) Not available Solubility in water (g/100 mL at 20°C) 20 Relative vapor density (air =1) 4.4 Molecular weight (g/mol) 127.26 aSource: International Programme on Chemical Safety (IPCS) INCHEM; International Chemical Safety Card No. 1444. Available at http://www.inchem.org. Accessed on 11-01-10. No reference dose (RfD), reference concentration (RfC), or cancer assessment for //,/7-di methyl cycl ohexyl amine is included on 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 (U.S. 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 //,//-dim ethyl cycl ohexyl amine. The toxicity of //, //-di methyl cycl ohexyl ami ne 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 //,//-dimethyl cycl ohexyl amine. No occupational exposure limits for //,/7-di methyl cycl ohexyl amine have been derived by the American Conference of 2 //,//-Dim ethyl cycl ohexyl amine ------- FINAL 5-19-2011 Governmental Industrial Hygienists (ACGIH, 2010), listed by the National Institute of Occupational Safety and Health (NIOSH, 2005), or adopted by the Occupational Safety and Health Administration (OSHA, 2010). The HEAST (U.S. EPA, 2003) does not report any cancer values for //,//-dimethyl cycl ohexyl amine. The International Agency for Research on Cancer (IARC, 2010) has not reviewed the carcinogenic potential of //,//-dimethylcyclohexyl amine. //,//-Dim ethyl cyclohexyl amine is not included in the 11th Report on Carcinogens (NTP, 2005). CalEPA (2009) has not prepared a quantitative estimate of carcinogenic potential for n, //-dimethyl cycl ohexyl amine. Literature searches were conducted on sources published from 1900 through May 3, 2011 for studies relevant to the derivation of provisional toxicity values for //, //-di m ethyl cycl ohexyl am i ne, CAS No. 98-94-2. 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, 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-, or chronic-duration) for development of toxicity values for //,//-dimethyl cycl ohexyl amine. DERIVATION OF PROVISIONAL VALUES Limitations in the available data preclude development of either cancer and noncancer toxicity values for //, //-di m ethyl cycl oh exyl am i ne. 3 //,//-Dimethyl cycl ohexyl amine ------- FINAL 5-19-2011 CANCER WEIGHT-OF-EVIDENCE (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). (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 05-03-11.. 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 05-03-11. 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. 595416. Accessed on 5/3/11. CalEPA (California Environmental Protection Agency). (2009) OEHHA toxicity criteria database. Office of Environmental Health Hazard Assessment, Sacramento, CA. Available online at http://vvvvvv.oehha.ca.gov/riskAChemicalDB/index.asp. 595417. Accessed on 5/3/11. 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 11-01-10. NIOSH (National Institute for Occupational Safety and Health). (2005) 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 11-01-10. 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 11-01-10. 4 //,//-Dim ethyl cyclohexyl amine ------- FINAL 5-19-2011 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 11-01-10. 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=6000lG8L.txt U.S. EPA (Environmental Protection Agency). (2003) 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; EPA 540-R-97-036. Available online at http://epa-heast.ornl.gov/. Accessed 11-01-10. 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 11-01-10. U.S. EPA (Environmental Protection Agency). (2010) 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 11-01-10. 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 11-01-10. 5 //,//-Dim ethyl cyclohexyl amine ------- |