DRAFT - DO NOT CITE OR QUOTE INCEA trackl"" n° f°r drafts or EPA ID for final] www.epa.gov/iris 4>EPA ANNOTATED REFERENCE OUTLINE FOR THE TOXICOLOGICAL REVIEW OF 2-Methylbutane (CAS No. 78-78-4) In Support of Summary Information on the Integrated Risk Information System (IRIS) 11/25/08 NOTICE This document is a draft. It has not been formally released by the U.S. Environmental Protection Agency and should not at this stage be construed to represent Agency position on this chemical. It is being circulated for review of its technical accuracy and science policy implications. U.S. Environmental Protection Agency Washington, DC ------- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 REVIEWS ACGIH (American Conference of Governmental Industrial Hygienists). (2001) Pentane (all isomers). ACGIH. Documentation of the threshold limit values and biological exposure indices 3. Cincinnati, OH. Anonymous. (1982) Final report of the safety assessment of isobutane, isopentane, n-butane, and propane. J Am Coll Toxicol 1(4): 127-142. Galvin, JB; Marashi, F. (1999) 2-methylbutane (isopentane). Cas# 78-78-4. J Toxicol Environ Health A 58(l-2):23-33. Starek, A. (2005) Pentane and its isomers. Documentation of proposed permissible occupational exposure values. Podstawy i Metody Oceny Srodowiska Pracy 21(2): 163-174. 2. CHEMICAL AND PHYSICAL INFORMATION Wilson, EW, Jr.; Hamilton, WA; Kennington, HR; et al. (2006) Measurement and estimation of rate constants for the reactions of hydroxyl radical with several alkanes and cycloalkanes. J Phys Chem A 110(10):3593-3604. 3. TOXICOKINETICS 3.1. ABSORPTION Dahl, AR; Damon, EG; Mauderly, JL; et al. (1988) Uptake of 19 hydrocarbon vapors inhaled by F344 rats. Fundam Appl Toxicol 10(2):262-269. 3.2. DISTRIBUTION 3.3. METABOLISM Chiba, S; Oshida, S. (1991) [Metabolism and toxicity of n-pentane and isopentane], Nihon Hoigaku Zasshi 45(2): 128-137. In Japanese with English summary. Frommer, U; Ullrich, V; Staudinger, H. (1970) Hydroxylation of aliphatic compounds by liver microsomes, I. Hoppe Seylers Z Physiol Chem 351(8):903-912. Frommer, U; Ullrich, V; Staudinger, H. (1970) Hydroxylation of aliphatic compounds by liver microsomes, II. Effect of phenobarbital induction in rats on specific activity and cytochrome p- 450 substrate binding spectra. Hoppe Seylers Z Physiol Chem 351(8):913-918. 3.4. ELIMINATION 3.5. PHYSIOLOGICALLY BASED TOXICOKINETIC MODELS 10/8/2009 2 DO NOT CITE OR QUOTE ------- 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 4. HAZARD IDENTIFICATION 4.1. STUDIES IN HUMANS—EPIDEMIOLOGY, CASE REPORTS, CLINICAL CONTROLS Oiso, N; Kawara, S; Kawada, A. (2008) Burn caused by isopentane and liquefied petroleum gas in an insecticide. J Eur Acad Dermatol Venereol [epub ahead of print; April 10, 2008], 4.2. LESS-THAN-LIFETIME AND CHRONIC STUDIES AND CANCER BIOASSAYS IN ANIMALS—ORAL AND INHALATION 4.2.1. Oral Haider, CA; Holdsworth, CE; Cockrell, BY; et al. (1985) Hydrocarbon nephropathy in male rats: identification of the nephrotoxic components of unleaded gasoline. Toxicol Ind Health 1(3):67- 87. 4.2.2. Inhalation Aranyi, C; O'Shea, WJ; Haider, CA; et al. (1986) Absence of hydrocarbon-induced nephropathy in rats exposed subchronically to volatile hydrocarbon mixtures pertinent to gasoline. Toxicol Ind Health 2(l):85-98. Haider, CA; Van Gorp, GS; Hatoum, NS; et al. (1986) Gasoline vapor exposures. Part II. Evaluation of the nephrotoxicity of the major C4/C5 hydrocarbon components. Am Ind Hyg Assoc J 47(3): 173-175. 4.3. REPRODUCTIVE/DEVELOPMENTAL STUDIES—ORAL AND INHALATION 4.4. OTHER ENDPOINT-SPECIFIC STUDIES 4.4.1. ACUTE AND SHORT-TERM TOXICITY 4.4.2. GENOTOXICITY STUDIES Kirwin, CJ; Thomas, WC; Simmon, VF. (1980) In vitro microbiological mutagenicity studies of hydrocarbon propellants. J Soc Cosmet Chem 31:367-370. 4.4.3. NEUROTOXICITY STUDIES 4.4.4. ENDOCRINE DISRUPTION 4.4.5. CONTACT SENSITIZATION 4.5. MECHANISTIC DATA AND OTHER STUDIES IN SUPPORT OF THE MODE OF ACTION 10/8/2009 3 DO NOT CITE OR QUOTE ------- 1 4.6. SYNTHESIS OF MAJOR NONCANCER EFFECTS 2 3 4.6.1. Oral 4 5 4.6.2. Inhalation 6 7 4.6.3. Mode of Action Information 8 9 4.7. EVALUATION OF CARCINOGENICITY 10 11 4.7.1. Summary of Overall Weight-of-Evidence 12 13 4.7.2. Synthesis of Human, Animal, and Other Supporting Evidence 14 15 4.7.3. Mode of Action Information 16 17 4.7.2.1. Hypothesized Mode of Action 18 19 4.7.2.2. Experimental Support for the Hypothesized Mode of Action 20 21 4.7.2.3. Other Possible Modes of Action 22 23 4.7.2.4. Conclusions About the Hypothesized Mode of Action 24 25 Support for the hypothesized mode of action in test animals 26 Relevance of the hypothesized mode of action to humans 27 Populations or lifestages particularly susceptible to the hypothesized mode of action 28 29 4.8. SUSCEPTIBLE POPULATIONS AND LIFE STAGES 30 31 4.8.3. Other 32 10/8/2009 4 DO NOT CITE OR QUOTE ------- |