United States Environmental Protection 1=1 m m Agency EPA/690/R-12/01 IF Final 6-21-2012 Provisional Peer-Reviewed Toxicity Values for 2,2-Dichloropropane (CASRN 594-20-7) 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 Chris Cubbison, PhD (Mentor) Custodio V. Muianga, PhD, MPH (Student Services Contractor) 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 3 MODE-OF-ACTION (MOA) DISCI SSION 4 REFERENCES 4 l 2,2-Dichloropropane ------- 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 2,2-Dichloropropane ------- FINAL 6-21-2012 PROVISIONAL PEER-REVIEWED TOXICITY VALUES 2,2-DICHLOROPROPANE (CASRN 594-20-7) 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 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.eov/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 2,2-Dichloropropane ------- FINAL 6-21-2012 INTRODUCTION 2,2-Dichloropropane (2,2-DCP; synonyms: acetone dichloride; isopropylidene chloride; dichlorodimethylmethane; dimethyldichloromethane) CAS No. 594-20-7, is a chloroalkane. Chloroalkanes are used as industrial solvents, for degreasing of metals, as fumigants or substitutes for terpenes, in dry cleaning, for soil sterilization, and as weed killers (Freitag et al.. 1994). Based on its high vapor pressure, 2,2-DCP is volatile. A table of physicochemical properties for 2,2-DCP is provided below (see Table 1). The molecular formula of 2,2-DCP is C3H6C12 and the chemical structure is shown in Figure 1. H3C CI CH, CI Figure 1. Structure of 2.2-DCP (NLM. 2011) Table 1. Physicochemical Properties of 2,2-DCP (CASRN 594-20-7)3 Property (unit) Value Boiling point (°C) 69.3 Melting point (°C) -35.0 Density (g/inL) (25°C) 1.082 Vapor pressure (atm at 25°C) 1.78 x 10"1 pH (unitless) ND Solubility in water (mg/L at 25°C) 391 (slightly soluble in water) Relative vapor density (air = 1) ND Molecular weight (g/mol) 112.99 aChemIDplusLite (2011): U.S. EPA (2007): WolframMathematica (2011). ND = no data. No reference dose (RfD), reference concentration (RfC), or cancer assessment for 2,2,-DCP is included in the U.S. Environmental Protection Agency (EPA) Integrated Risk Information System (IRIS) (U.S. EPA 2011b) or on the Drinking Water Standards and Health Advisories List (U.S. EPA 2011a). No RfD or RfC values are reported in the Health Effects Assessment Summary Tables (HEAST) (U.S. EPA 2003). The Chemical Assessments and Related Activities (CARA) database does not include a Health and Environmental Effects Profile (HEEP) for 2,2,-DCP (U.S. EPA 1994). The toxicity of 2,2,-DCP has not been reviewed by the Agency for Toxic Substances and Disease Registry (ATSDR 2011) or the World Health Organization (WHO. 2011). The California Environmental Protection Agency (Cal EPA. 2011. 2008) has not derived toxicity values for exposure to 2,2-DCP. No occupational exposure limits for 2,2,-DCP 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). 2 2,2-Dichloropropane ------- FINAL 6-21-2012 The HEAST (U.S. EPA. 2003) does not report any values. The International Agency for Research on Cancer (IARC, 2011) has not reviewed the carcinogenic potential of 2,2,-DCP. 2,2,-DCP is not included in the 12th Report on Carcinogens (N I P. 2011). Cal EPA (2009) has not prepared a quantitative estimate of the carcinogenic potential of 2,2,-DCP. Literature searches were conducted on sources published from 1900 through May 2012 for studies relevant to the derivation of provisional toxicity values for 2,2-DCP, CAS No. 594-20-7. The following databases were searched by chemical name, synonyms, or CAS No.: ACGM, ANEUPL, ATSDR, BIOSIS, Cal EPA, CCRIS, CDAT, ChemlDplus, CIS, CRISP, DART, EMIC, EPIDEM, ETICBACK, FEDRIP, GENE-TOX, HAPAB, HERO, HMTC, HSDB, IARC, INCHEM IPCS, IP A, ITER, IUCLID, LactMed, NIOSH, NTIS, NTP, OSHA, OPP/RED, PESTAB, PPBIB, PPRTV, PubMed (toxicology subset), RISKLINE, RTECS, TOXLINE, TRI, U.S. EPA IRIS, U.S. EPA HEAST, U.S. EPA HEEP, U.S. EPA OW, and U.S. EPA TSCATS/TSCATS2. The following databases were searched for toxicity values or exposure limits: ACGIH, ATSDR, Cal EPA, 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. REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER) No information is available regarding repeat-dose oral or inhalation exposure of humans or animals to 2,2-DCP. An in vitro study by Tornero-Velez et al. (2004) investigated the metabolism rates of 2,2-DCP and 1,3-DCP in rat liver microsomes and cytosol based on P450 and GST pathways in clearance and activation using gas chromatography. No metabolism of 2,2-DCP via a GSH-dependent conjugation pathway was observed, and the study authors observed only a minor level of clearance via the P450 pathway (7 x 10 4L/h/mg microsomal protein). 2,2-DCP was not mutagenic in various strains of Salmonella, including those containing GSTT1-1, indicating that GSTT1-1 does not produce mutagenic metabolites (Torne-Velez et al., 2004). Frietag et al. (1994) reported structural configurations and potential influence on the toxicity of chloroalkanes including 2,2-DCP; however, the available data are insufficient to perform a toxicity assessment of 2,2-DCP. Additionally, a preliminary structure-activity relationship (SAR) analysis for this chemical did not suggest a reliable surrogate chemical at this time. DERIVATION OF PROVISIONAL VALUES Limitations in the available data preclude development of both cancer and noncancer toxicity values. CANCER WEIGHT-OF-EVIDENCE (WOE) DESCRIPTOR Limitations in the available data preclude development of a WOE descriptor. 3 2,2-Dichloropropane ------- FINAL 6-21-2012 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. http ://www. acgih.org/ store/ProductDetail. cfm?id=2147 ATSDR (Agency for Toxic Substances and Disease Registry). (2011). Toxicological profiles: Information about contaminants found at hazardous waste sites. Available online at http://www.atsdr.cdc.gov/toxprofiles/index.asp Cal EPA (California Environmental Protection Agency). (2008). OEHHA acute, 8-hour and chronic Reference Exposure Levels (chRELs) [Database], Retrieved from http://www.oehha.ca.gov/air/allrels.html Cal EPA (California Environmental Protection Agency). (2009). Appendix A: Hot spots unit risk and cancer potency values. Sacramento, CA: Office of Environmental Health Hazard Assessment, http://www.oehha.ca.gov/air/hot spots/2009/AppendixA.pdf Cal EPA (California Environmental Protection Agency). (2011). OEHHA toxicity criteria database. Sacramento, CA. http://www.oehha.ca. gov/tcdb/ Freitag, D; Ballhorn, L; Behechti, A; Fischer, K; Thumm, W. (1994). Structural configuration and toxicity of chlorinated alkanes. Chemosphere 28: 253-259. http://dx.doi.org/ 3045-6535(94)90122-8 IARC (International Agency for Research on Cancer). (2011). IARC Monographs on the evaluation of carcinogenic risk to humans. Available online at http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php NIOSH (National Institute for Occupational Safety and Health). (2007). NIOSH pocket guide to chemical hazards. (2005-149). Cincinnati, OH. NLM (National Institutes of Health, National Library of Medicine). (2011). ChemlDplus Lite: 2,2-dichloropropane [Database], Bethesda, MD: National Library of Medicine. Retrieved from http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.isp NTP (National Toxicology Program). (2011). Report on carcinogens: Twelfth edition. Washington, DC: U.S. Department of Health and Human Services. http://ntp.niehs.nih.gov/ntp/roc/twelfth/rocl2.pdf 4 2,2-Dichloropropane ------- FINAL 6-21-2012 OSHA (Occupational Safety & Health Administration). (2006). Table Z-l limits for air contaminants. Occupational Safety and Health Administration. http://www.osha.gov/pls/oshaweb/owadisp.show docuinent?p table=STANDARDS&p id=9992 Tornero-Velez, R; Ross, MK; Granville, C; Laskey, J; Jones, JP; Demarini, DM; Evans, MV. (2004). Metabolism and mutagenicity of source water contaminants 1,3-dichloropropane and 2,2-dichloropropane. Drug Metab Dispos 32: 123-131. http://dx.doi.org/10.1124/dmd.32.L123 U.S. EPA (U.S. Environmental Protection Agency). (1994). Chemical assessments and related activities (CARA) [EPA Report], (600R94904; OHEA-I-127). Washington, DC. http://nepis.epa. gov/Exe/ZyPURL.cgi?Dockev=6000 lG8L.txt U.S. EPA (U.S. Environmental Protection Agency). (2003). Health Effects Assessment Summary Tables (HEAST). Available online at http://epa-h.east.oml.gov/ U.S. EPA (U.S. Environmental Protection Agency). (2007). Draft risk assessment for the Siemens Water Technologies Corp. carbon reactivation facility, Parker, Arizona: Appendix F: Chemical-physical parameters for compounds not included in USEPA's HHRAP [EPA Report], San Francisco, CA. http://www.epa.gov/region9/waste/siemens/pdf/RiskAssessment/siemens- riskassessAppxF.pdf U.S. EPA (U.S. Environmental Protection Agency). (201 la). 2011 Edition of the drinking water standards and health advisories. (EPA 820-R-11-002). Washington, DC. http://water.epa.gov/action/advisories/drinking/drinking index.cfm U.S. EPA (U.S. Environmental Protection Agency). (2011b). Integrated Risk Information System (IRIS). Available online at http://www.epa.gov/IRIS/ WHO (World Health Organization). (2011). Online catalog for the Environmental Health Criteria Series. Available online at http://www.who.int/ipcs/publications/ehc/en/ Wolfram Mathematica (Wolfram Mathematica Documentation Center). (2011). 2,2- dichloropropane [Fact Sheet], Champaign, IL: Wolfram Research Company. http://www.wolframalpha.eom/entities/chemicals/2.2-dichloropropane/4i/bh/kc/ 5 2,2-Dichloropropane ------- |