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United States Environmental Protection ^^LbI M % Agency EPA/690/R-05/018F Final 4-15-2005 Provisional Peer Reviewed Toxicity Values for m-Phthalic acid (CASRN 121-91-5) Superfund Health Risk Technical Support Center National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati, OH 45268 ------- 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 i.v. intravenous IRIS Integrated Risk Information System IUR inhalation unit risk 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 1 ------- MTD maximum tolerated dose MTL median threshold limit NAAQS National Ambient Air Quality Standards NOAEL no-observed-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-observed-effect level OSF oral slope factor p-IUR provisional inhalation unit risk p-OSF provisional oral slope factor p-RfC provisional inhalation reference concentration 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 ------- 4-15-05 PROVISIONAL PEER REVIEWED TOXICITY VALUES FOR jm-PHTHALIC ACID (CASRN 121-91-5) 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 science and available information evolve, PPRTVs are initially derived with a three-year life-cycle. However, EPA Regions (or the EPA HQ Superfund Program) sometimes request that a frequently used PPRTV be reassessed. 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. 1 ------- 4-15-05 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. 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 The HEAST (U.S. EPA, 1997) reports that data are inadequate for quantitative risk assessment of m-phthalic acid. There is no listing for m-phthalic acid on IRIS (U.S. EPA, 2003) or in the Drinking Water Standards and Health Advisories list (U.S. EPA, 2002). The CARA lists (U.S. EPA, 1991, 1994) report a HEEP for Phthalic Acids (U.S. EPA, 1986). ATSDR (2003) has not published a Toxicological Profile for m-phthalic acid, and no Environmental Health Criteria Document is available (WHO, 2003). ACGIH (2003), NIOSH (2003), and OSHA (2003) have not developed occupational exposure limits for m-phthalic acid. Neither IARC (2003) nor NTP (2003) have evaluated the carcinogenicity of m-phthalic acid. Literature searches were conducted from 1985 through August, 2003 for studies relevant to the derivation of provisional toxicity values for m-phthalic acid. Databases searched included: TOXLINE (supplemented with NTIS and BIOSIS updates), MEDLINE, CANCERLIT, TSCATS, RTECS, 2 ------- 4-15-05 CCRIS, DART/ETICBACK, EMIC/EMICBACK, HSDB, and GENETOX. Additional literature searches from August 2003 through October 2004 were conducted by NCEA-Cincinnati using MEDLINE, TOXLINE, Chemical and Biological Abstracts databases. REVIEW OF PERTINENT DATA Human Studies No studies of the toxicity of m-phthalic acid in humans were located in the available literature. Animal Studies No studies of the subchronic or chronic toxicity of m-phthalic acid in animals were located in the available literature. DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC ORAL RfD VALUES FOR m-PHTHALIC ACID In the absence of subchronic or chronic data on the oral toxicity of m-phthalic acid in humans or animals, derivation of provisional subchronic or chronic RfD values is precluded. DERIVATION OF PROVISIONAL SUBCHRONIC AND CHRONIC INHALATION RfC VALUES FOR jm-PHTHALIC ACID In the absence of subchronic or chronic data on the inhalation toxicity of m-phthalic acid in humans or animals, derivation of provisional subchronic or chronic RfC values is precluded. DERIVATION OF A PROVISIONAL CARCINOGENICITY ASSESSMENT FOR jm-PHTHALIC ACID Data on the carcinogenic effects of m-phthalic acid in humans or animals are not available. Under the new Guidelines for Carcinogen Risk Assessment (U.S. EPA, 2005), the data are inadequate for an assessment of human carcinogenic potential for o-phthalic acid. 3 ------- 4-15-05 REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists). 2003. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. ACGIH, Cincinnati, OH. ATSDR (Agency for Toxic Substances and Disease Registry). 2003. Internet HazDat- Toxicological Profile Query. Online, http://www.atsdr.cdc.gov/toxpro2.html IARC (International Agency for Research on Cancer). 2003. Search IARC Monographs. Online. http://193.51.164.ll/cgi/iHound/Chem/iH Chem Frames.html NIOSH (National Institute for Occupational Safety and Health). 2003. Online NIOSH Pocket Guide to Chemical Hazards. Online, http://www.cdc.gov/niosh/npg/npgdcas.html NTP (National Toxicology Program). 2003. Management Status Report. Online. http://ntp-server.niehs.nih.gov/cgi/iH Indexes/ATI, SRCH/iH ATI, SRCH Frames.html OSHA (Occupational Safety and Health Administration). 2003. OSHA Standard 1910.1000 Table Z-l. Part Z, Toxic and Hazardous Substances. Online. http://www.osha-slc.gov/OshStd data/1910 1000 TABLE Z-l.html U.S. EPA. 1986. Health and Environmental Effects Profile for Phthalic Acids (o-, m-, p-). Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response, Washington, DC. U.S. EPA. 1991. Chemical Assessments and Related Activities (CARA). Office of Health and Environmental Assessment, Washington, DC. April, 1991. U.S. EPA. 1994. Chemical Assessments and Related Activities (CARA). Office of Health and Environmental Assessment, Washington, DC. December, 1994. 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. 2002. 2002 Edition of the Drinking Water Standards and Health Advisories. Office of Water, Washington, DC. Summer, 2002. EPA 822-R-02-038. Online. http ://www.epa. gov/waterscience/drinking/ standards/dwstandards .pdf 4 ------- 4-15-05 U.S. EPA. 2003. Integrated Risk Information System (IRIS). Office of Research and Development. National Center for Environmental Assessment, Washington, DC. Online. http://www.epa.gov/iris/ U.S. EPA. 2005. Guidelines for Carcinogen Risk Assessment. Office of Research and Development, National Center for Environmental Assessment, Washington, DC. EPA/63 0/P-03/001F. WHO (World Health Organization). 2003. Online catalogs for the Environmental Health Criteria Series. Online, http://www.who.int/dsa/cat97/zehcl.htm 5 ------- |