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)


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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

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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
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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
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1	4.6. SYNTHESIS OF MAJOR NONCANCER EFFECTS
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3	4.6.1. Oral
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5	4.6.2. Inhalation
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7	4.6.3. Mode of Action Information
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9	4.7. EVALUATION OF CARCINOGENICITY
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11	4.7.1. Summary of Overall Weight-of-Evidence
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13	4.7.2. Synthesis of Human, Animal, and Other Supporting Evidence
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15	4.7.3. Mode of Action Information
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17	4.7.2.1. Hypothesized Mode of Action
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19	4.7.2.2. Experimental Support for the Hypothesized Mode of Action
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21	4.7.2.3. Other Possible Modes of Action
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23	4.7.2.4. Conclusions About the Hypothesized Mode of Action
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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
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29	4.8. SUSCEPTIBLE POPULATIONS AND LIFE STAGES
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31	4.8.3. Other
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