United States Environmental Protection 1=1 m m Agency EPA/690/R-08/014F Final 7-08-2008 Provisional Peer Reviewed Toxicity Values for Endrin aldehyde (CASRN 7421-93-4) Superfund Health Risk Technical Support Center National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati, OH 45268 ------- Acronyms and Abbreviations bw body weight cc cubic centimeters CD Caesarean Delivered CERCLA Comprehensive Environmental Response, Compensation and Liability Act of 1980 CNS central nervous system cu.m cubic meter DWEL Drinking Water Equivalent Level FEL frank-effect level FIFRA Federal Insecticide, Fungicide, and Rodenticide Act g grams GI gastrointestinal HEC human equivalent concentration Hgb hemoglobin i.m. intramuscular i.p. intraperitoneal IRIS Integrated Risk Information System IUR inhalation unit risk i.v. intravenous kg kilogram L liter LEL lowest-effect level LOAEL lowest-observed-adverse-effect level LOAEL(ADJ) LOAEL adjusted to continuous exposure duration LOAEL(HEC) LOAEL adjusted for dosimetric differences across species to a human m meter MCL maximum contaminant level MCLG maximum contaminant level goal MF modifying factor mg milligram mg/kg milligrams per kilogram mg/L milligrams per liter MRL minimal risk level MTD maximum tolerated dose MTL median threshold limit NAAQS National Ambient Air Quality Standards NOAEL no-ob served-adverse-effect level NOAEL(ADJ) NOAEL adjusted to continuous exposure duration NOAEL(HEC) 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 inhalation reference concentration 1 ------- p-RfD provisional oral reference dose PBPK physiologically based pharmacokinetic ppb parts per billion ppm parts per million PPRTV Provisional Peer Reviewed Toxicity Value RBC red blood cell(s) RCRA Resource Conservation and Recovery Act RDDR Regional deposited dose ratio (for the indicated lung region) REL relative exposure level RfC inhalation reference concentration RfD oral reference dose RGDR Regional gas dose ratio (for the indicated lung region) s.c. subcutaneous SCE sister chromatid exchange SDWA Safe Drinking Water Act sq.cm. square centimeters TSCA Toxic Substances Control Act UF uncertainty factor Hg microgram |j,mol micromoles voc volatile organic compound 11 ------- 7-8-2008 PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR ENDRIN ALDEHYDE (CASRN 7421-93-4) Background On December 5, 2003, the U.S. Environmental Protection Agency's (EPA's) 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 (PPRTV) 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 Integrated Risk Information System (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 two EPA scientists and external peer review by three independently selected scientific experts. PPRTVs differ from IRIS values in that PPRTVs do not receive the multi-program 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 five-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 manuscripts 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 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 in question. PPRTVs are periodically updated; therefore, users should ensure that the values contained in the PPRTV are current at the time of use. 1 ------- 7-8-2008 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 manuscript 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 Except as noted, literature searches were conducted from the 1960s through December 2007 for studies relevant to the derivation of provisional toxicity values for endrin aldehyde. Databases searched include MEDLINE, TOXLINE (Special), BIOSIS (from August 2000), TSCATS 1/TSCATS 2, CCRIS, DART/ETIC, GENETOX, HSDB, RTECS, and Current Contents (July through December 2007). This document has passed the STSC quality review and evaluation indicating that the quality is consistent with the SOPs and standards of the STSC and is suitable for use by registered users of the PPRTV system. No RfD, RfC, or carcinogenicity assessment for endrin aldehyde is available on IRIS (U.S. EPA, 2008), in the Drinking Water Standards and Health Advisories list (U.S. EPA, 2006), or in the HEAST (U.S. EPA, 1997). The CARA list (U.S. EPA, 1991, 1994) does not include any documents for endrin aldehyde either. Documents listed for endrin include a Health Effects Assessment (U.S. EPA, 1987) and a Drinking Water Criteria Document (U.S. EPA, 1992) neither of which contain chronic or subchronic toxicity data for endrin aldehyde. The ATSDR Toxicological Profile for endrin (ATSDR, 1996) includes endrin aldehyde, but it does not contain any chronic or subchronic toxicity data. The chronic toxicity and carcinogenicity of endrin aldehyde were not assessed by IARC (2008) or NTP (2008), and endrin aldehyde is not included in the 11th Report on Carcinogens (NTP, 2005). An Environmental Health Criteria document (WHO, 1992) for endrin was consulted for relevant information. Literature searches were conducted from the 1960s through December 2007 for studies relevant to the derivation of provisional toxicity values for endrin aldehyde. Databases searched include MEDLINE, TOXLINE (Special), BIOSIS, TSCATS/TSCATS 2, CCRIS, DART/ETIC, GENETOX, HSDB, RTECS, and Current Contents. 2 ------- 7-8-2008 FEASIBILITY OF DERIVING A PROVISIONAL RfD FOR ENDRIN ALDEHYDE The data are inadequate to derive a p-RfD for endrin aldehyde. No dose-response information pertinent to any target organs is available in the current database; thus, the database lacks a study that could serve as a suitable basis for the derivation of a p-RfD for endrin aldehyde. FEASIBILITY OF DERIVING A PROVISIONAL RfC FOR ENDRIN ALDEHYDE No inhalation toxicity data in humans or animals is identified; thus, no p-RfC could be derived for endrin aldehyde. PROVISIONAL CARCINOGENICITY ASSESSMENT FOR ENDRIN ALDEHYDE Because of the lack of carcinogenic data in humans or animals, under the 2005 Guidelines for Carcinogen Risk Assessment (U.S. EPA, 2005), this PPRTV document classifies endrin aldehyde as having "Inadequate Information to Assess Carcinogenic Potential FEASIBILITY OF DERIVING A PROVISIONAL ORAL SLOPE FACTOR OR INHALATION UNIT RISK FOR ENDRIN ALDEHYDE Neither a p-OSF nor a p-IUR could be derived for endrin aldehyde because of the lack of suitable oral or inhalation data in both humans and animals. REFERENCES ATSDR (Agency for Toxic Substances and Disease Registry). 1996. Toxicological Profile for Endrin. Update. August 1996. ATSDR, U.S. Public Health Service, Atlanta, GA. IARC (International Agency for Research on Cancer). 2008. Search IARC Monographs. Online. http://monographs.iarc.fr/ENG/Monographs/allmonos90.php. 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 at http://ntp-server.niehs.nih.gov/. NTP (National Toxicology Program). 2008. Management Status Report. Online. http://ntp.niehs.nih.gov/index.cfm?obiectid=78CC7E4C-FlF6-975E-72940974DE301C3F. U.S. EPA. 1987. Health Effects Assessment for Endrin. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Emergency and Remedial Response, Washington, DC. 3 ------- 7-8-2008 U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and Environmental Assessment, Washington, DC. U.S. EPA. 1992. Drinking Water Criteria Document for Endrin. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Water, Washington, DC. NTIS PB92-173384. U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and Environmental Assessment, Washington, DC. December. U.S. EPA. 1997. Health Effects Assessment Summary Tables. FY-1997 Update. 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. July. EPA/540/R-97/036. NTIS PB97-921199. U.S. EPA. 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. U.S. EPA. 2006. 2006 Edition of the Drinking Water Standards and Health Advisories. Office of Water, Washington, DC. EPA 822-R-06-013. Washington, DC. http://www.epa.gov/waterscience/drinking/standards/dwstandards.pdf. U.S. EPA. 2008. Integrated Risk Information System (IRIS). Office of Research and Development, National Center for Environmental Assessment, Washington, DC. Online. http ://www. epa. gov/iri s/. WHO (World Health Organization). 1992. Endrin. Environmental Health Criteria 130. Geneva, Switzerland. 4 ------- |