United States kS^laMIjk Environmental Protection ^J^iniiil m11 Agency EPA/690/R-12/003F Final 3-20-2012 Provisional Peer-Reviewed Toxicity Values for tert-Butyl Formate (CASRN 762-75-4) Superfund Health Risk Technical Support Center National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati, OH 45268 ------- 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). l tert-Butyl formate ------- TABLE OF CONTENTS COMMONLY USED ABBREVIATIONS iii 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 DISCUSSION 3 REFERENCES 3 li tert-Butyl formate ------- 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 111 tert-Butyl formate ------- FINAL 3-20-2012 PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR tert-BUTYL FORMATE (CASRN 762-75-4) 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 tert-Butyl formate ------- FINAL 3-20-2012 INTRODUCTION No reference dose (RfD), reference concentration (RfC), or cancer assessment for tert-butyl formate is included in the U.S. Environmental Protection Agency (EPA) Integrated Risk Information System (IRIS) (U.S. EPA, 201 lb) or on the Drinking Water Standards and Health Advisories List (U.S. EPA, 201 la). 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) list does not include a Health and Environmental Effects Profile (HEEP) for tert-butyl formate and, thus, does not describe the potential carcinogenicity of tert-butyl formate or derive noncancer toxicity values for tert-butyl formate (U.S. EPA, 1994). The toxicity of tert-butyl formate 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 tert-butyl formate. No occupational exposure limits for tert-butyl formate 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, 2003) does not report any U.S. EPA (1986) cancer weight-of-evidence (WOE) classifications for /f/ /-butyl formate. The International Agency for Research on Cancer (IARC, 2011) has not reviewed the carcinogenic potential of tert-butyl formate, tert-Butyl formate is not included in the 12th Report on Carcinogens (NTP, 2011). CalEPA (2009) has not prepared a quantitative estimate of the carcinogenic potential of tert-butyl formate. Literature searches were conducted on sources published from 1900 through January 2012, for studies relevant to the derivation of provisional toxicity values for tert-butyl formate, CAS No. 762-75-4. 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 risk assessment 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 tert-Butyl formate ------- FINAL 3-20-2012 REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER) No information is available regarding repeat-dose oral or inhalation exposure of humans or animals to tert-butyl formate. 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 DISCUSSION Limitations in the available data preclude determination of a mode-of-action discussion. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists). (201 1). 201 1 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/Product Detai 1. cfm?id=2147. AT SDR (Agency for Toxic Substances and Disease Registry). (201 1). Toxicological profiles: Information about contaminants found at hazardous waste sites, from http://www.atsdr.cdc.gov/toxprofiles/index.asp Cat 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 Cat 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). (201 1). OEHHA toxicity criteria database. Sacramento, CA: Office of Environmental Health Hazard Assessment. http ://www. oehha.ca. gov/tcdb/. 3 tert-Butyl formate ------- FINAL 3-20-2012 I ARC (International Agency for Research on Cancer). (201 1). I ARC Monographs on the evaluation of carcinogenic risk to humans, from http://monoeraphsiarc.fr/ENG/Monoeraphs/PDFs/index.php. NIOSH (National Institute for Occupational Safety and Health). (2007). NIOSH pocket guide to chemical hazards. (2005-149). Cincinnati, OH. NTP (National Toxicology Program). (201 1). 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. 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 document?p tabte=STANDARDS&p id=9992. U.S. EPA (U.S. Environmental Protection Agency). (1986). Guidelines for carcinogen risk assessment. (EPA/630/R-00/004). Washington, DC: U.S. Environmental Protection Agency, Risk Assessment Forum. http://epa.gov/raf/publications/pdfs/CA%20GUlDELINES 1986.PDF. U.S. EPA (U.S. Environmental Protection Agency). (1994). Chemical assessments and related activities (CARA). (600R94904; OHEA-I-127). Washington, DC: Office of Health and Environmental Assessment, Office of Research and Development. http://nepis.epa. eov/Exe/ZyPURL.cei?Dockev=6000 lG8L.txt. U.S. EPA (U.S. Environmental Protection Agency). (2003). Health Effects Assessment Summary Tables (HEAST), from http://epa-heast.ornl.gov/. U.S. EPA (U.S. Environmental Protection Agency). (201 la). 201 1 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). (201 lb). Integrated Risk Information System (IRIS), from http://www.epa.gov/1 RIS/. WHO (World Health Organization). (201 1). Online catalog for the Environmental Health Criteria Series, from http://www.who.int/ipcs/publications/ehc/en/. 4 tert-Butyl formate ------- |