United States Environmental Protection 1=1 m m Agency EPA/690/R-12/015F Final 7-12-2012 Provisional Peer-Reviewed Toxicity Values for Endrin Ketone (CASRN 53494-70-5) 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 J. Phillip Kaiser, 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). ------- 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 WOE DESCRIPTOR 3 MODE-OF-ACTION (MOA) DISCUSSION 3 REFERENCES 3 l Endrin Ketone ------- COMMONLY USED ABBREVIATIONS BMC benchmark concentration BMCL benchmark concentration lower bound 95% confidence interval BMD benchmark dose 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 POD point of departure p-OSF provisional oral slope factor p-RfC provisional reference concentration (inhalation) p-RfD provisional reference dose (oral) 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 Endrin Ketone ------- FINAL 7-12-2012 PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR ENDRIN KETONE (CASRN 53494-70-5) 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). 1 Endrin Ketone ------- FINAL 7-12-2012 INTRODUCTION No reference dose (RfD), reference concentration (RfC), or cancer assessment for endrin ketone is included in the U.S. Environmental Protection Agency (U.S. EPA) Integrated Risk Information System (IRIS) (U.S. EPA, 201 la) or on the Drinking Water Standards and Health Advisories List (U.S. EPA, 201 lb). No RfD or RfC values are reported in the Health Effects Assessment Summary Tables (HEAST) (U.S. EPA, 201 lc). The Chemical Assessments and Related Activities (CARA) list does not include a Health and Environmental Effects Profile (HEEP) for endrin ketone (U.S. EPA, 1994). The toxicity of endrin ketone has not been independently reviewed by the Agency for Toxic Substances and Disease Registry (ATSDR, 2011) or the World Health Organization (WHO, 2011). However, because endrin ketone is a major breakdown product of endrin, assessments of the parent compound include studies with human exposure and/or toxicity data for endrin ketone when available (i.e., ATSDR 1996 and WHO 2004). The California Environmental Protection Agency (CalEPA, 2008, 2011) has not derived toxicity values for exposure to endrin ketone. No occupational exposure limits for endrin ketone have been derived or recommended by the American Conference of Governmental Industrial Hygienists (ACGIH, 2011), the National Institute for Occupational Safety and Health (NIOSH, 2007), or the Occupational Safety and Health Administration (OSHA, 2006). The HEAST (U.S. EPA, 201 lc) does not report a U.S. EPA (1986) cancer weight-of-evidence classification (WOE) for endrin ketone. The International Agency for Research on Cancer (IARC, 2011) has not reviewed the carcinogenic potential of endrin ketone. Endrin ketone is not included in the 12th Report on Carcinogens (NTP, 2011). CalEPA (2009) has not prepared a quantitative estimate of the carcinogenic potential of endrin ketone. Literature searches were conducted on sources published from 1900 through April 2012 for studies relevant to the derivation of provisional toxicity values for endrin ketone, CAS No. 53494-70-5. Searches were conducted using U.S. 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 toxicity values: ACGIH, ATSDR, CalEPA, U.S. EPA IRIS, U.S. EPA HEAST, U.S. EPA HEEP, U.S. EPA OW, U.S. EPA TSCATS/TSCATS2, NIOSH, NTP, OSHA, and RTECS. 2 Endrin Ketone ------- FINAL 7-12-2012 REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER) No usable information is available regarding repeat-dose oral or inhalation exposure of humans or animals to endrin ketone. A material safety data sheet reports an oral LD50 of 10 mg/kg in rats (CHEMWATCH, 2008), but the study giving rise to the value is not indentified, nor was it able to be located. However, an LD50 having the same value and species (10 mg/kg in rat) is present in an ATSDR (1996) report, but the value listed is for endrin—not endrin ketone. There is one available short-term study in rats. The study by Young and Mehendale (1986) exposed three male and female rats via diet for 15 days to endrin ketone at a concentration of 5 ppm. This study cannot be used as a principal study to derive a reference value for endrin ketone because it only employs a single dose for a short-term duration. DERIVATION OF PROVISIONAL VALUES Limitations in the available data preclude development of cancer and 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) 2011 TLVs and BEIs: Based on the documentation of the threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinnati, OH: ACGIH. Available online at http://www.acgih.org/store/ProductDetai 1.cfm?id=2147. 783980. ATSDR (Agency for Toxic Substances and Disease Registry). (1996) Toxicological profile for endrin. U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA. Available online at http://www.atsdr.cdc.gov/ToxProfiles/tp89.pdf. 784052. 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 September8, 2011. 684152. 3 Endrin Ketone ------- FINAL 7-12-2012 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 September 8, 2011. 595416. CalEPA (California Environmental Protection Agency). (2009) 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. 684164. CalEPA (California Environmental Protection Agency). (2011) OEHHA toxicity criteria database. Office of Environmental Health Hazard Assessment, Sacramento, CA. Available online at http://www.oehha.ca.gov/tcdb. Accessed on September 8, 2011. 783987. CHEMWATCH. (2008) Endrin ketone. Material safety sheet, sc-257412. Santa Cruz Biotechnology, Inc, Santa Cruz, CA. Available online at http://datasheets.scbt.com/sc- 257412.pdf. IARC (International Agency for Research on Cancer). (2011) IARC monographs on the evaluation of carcinogenic risks to humans. Available online at http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php. Accessed on September 8, 2011. 783869. NIOSH (National Institute for Occupational Safety and Health). (2007) NIOSH pocket guide to chemical hazards. Department of Health and Human Services, National Institute for Occupational Safety and Health, Cincinnati, OH; DHHS (NIOSH) publication no. 2005-149. Available online at http://www.cdc.gov/niosh/docs/2005-149/. Accessed on September 8, 2011. 192177. NTP (National Toxicology Program). (2011) Report on carcinogens, twelfth edition. U.S. Department of 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/twelfth/rocl2.pdf. Accessed on September 8, 2011. 737606. OSHA (Occupational Safety and Health Administration). (2006) Table Z-l limits for air contaminants: occupational safety and health standards, subpart Z, toxic and hazardous substances. U.S. Department of Labor, Washington, DC; OSHA Standard 1910.1000. Available online at http://63.234.227.130/pls/oshaweb/owadisp.show document?p table=STANDARDS& p id=9992. Accessed on September 8, 2011. 670067. U.S. EPA (Environmental Protection Agency). (1986) Guidelines for carcinogen risk assessment. Risk Assessment Forum, Washington, DC; EPA/630/R-00/004. September 1986. Available online at http://epa.gov/raf/publications/pdfs/CA%20GUIDELINES 1986.PDF. 199530. 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/ZvPURL.cgi?Dockey=6000lG8L.txt. 596444. 4 Endrin Ketone ------- FINAL 7-12-2012 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 September 8, 2011. 003752. U.S. EPA (Environmental Protection Agency). (201 lb) 2011 Edition of the drinking water standards and health advisories. Office of Water, Washington, DC; EPA/820/R-11/002. Available online at http://water.epa.gov/action/advisories/drinkine/drinkine index.dm. Accessed September 8, 2011. 783978. U.S. EPA (Environmental Protection Agency). (201 lc) Health effects assessment summary tables (HEAST). Office of Research and Development, Office of Emergency and Remedial Response, Washington, DC. Available online at http://epa-heast.ornl.eov/. Accessed on September 8, 2011. 595422. WHO (World Health Organization). (2004) Endrin in drinking-water: background document for development of WHO guidelines for drinking-water quality. WHO/SDE/WSH/03.04/93, WHO, Geneva, Switzerland. Available online at http://www.who.int/water sanitation health/dwq/chemicals/endrin/en/. Accessed September 8, 2011. 783977. 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 September 8, 2011. 595424. Young, RA; Mehendale, HM. (1986) Effect of endrin and endrin derivatives on hepatobiliary function and carbon tetrachloride-induced hepatotoxicity in male and female rats. Fd Chem Toxic 24(8):863-868. 784047. 5 Endrin Ketone ------- |