ANNOTATED REFERENCE OUTLINE FOR THE TOXICOLOGICAL REVIEW OF 2-Methylpentane (CAS No. 107-83-5) 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-Methylpentane
(CAS No. 107-83-5)
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
Abbritti, G; Siracusa, A; Cianchetti, C; et al. (1976) Shoe-makers' polyneuropathy in Italy: the
aetiological problem. Br J Ind Med 33(2):92-99.
Anonymous. (1998) Gasoline (aug 1996). Beratergremium fuer umweltrelevante Altstoffe 200.
Dutch Expert Committee on Occupational Standards. (1993) Health-based recommended
occupational exposure limit for 2-methylpentane, 3-methylpentane, 2,2-dimethylbutane,
2,3-dimethylbutane (hexane isomers). Directorate General of Labour, the Netherlands 7(93).
SDU Uitgeverij Plantijnstraat, Afdeling Verkoop Publikaties Arbeidsinspectie, Postbus
20014(2500).
Galvin, JB. (1997) Toxicity data for commercial hexane and hexane isomers. Technology and
Solvents for Extracting Oilseeds and Nonpetroleum Oils:75-85.
Galvin, JB; Bond, G. (1999) 2-methylpentane (isohexane). Cas# 107-83-5. J Toxicol Environ
Health A 58(l-2):81-92.
Gobba, F; Ghittori, S; Imbriani, M; et al. (1997) The urinary excretion of solvents and gases for
the biological monitoring of occupational exposure: A review. Sci Total Environ 199(l-2):3-12.
Levy, LS; Lee, WR. (1994) Aliphatic chemicals. Raffle, PAB; ed. Hunter's Diseases of
Occupations, 8th Edition. Edward Arnold: London, England, UkLittle, Brown and Co.: Boston,
MA, 139-190.
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.
Tsuruta, H. (1982) Percutaneous absorption of organic solvents. III. On the penetration rates of
hydrophobic solvents through the excised rat skin. Ind Health 20(4):335-345.
3.2.	DISTRIBUTION
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3.3. METABOLISM
Bartolucci, GB; De Rosa, E; Gori, G; et al. (1991) Use of urinary metabolites as indicators of
exposure to solvents. In: Rantanen, J; Lehtinen, S; eds. International Congress Series, 890. New
Trends and Developments in Occupational Health Services International Symposium, Espoo,
Finland, October 3-6, 1989. New York, NY: Elsevier Science Publishing Co., Inc.
Bartolucci, GB; Perbellini, L; Gori, GP; et al. (1986) Occupational exposure to solvents field
comparison of active and passive samplers and biological monitoring of exposed workers. Ann
Occup Hyg 30(3):295-306.
Kawai, T; Mizunuma, K; Yasugi, T; et al. (1995) Monitoring of exposure to methylpentanes by
diffusive sampling and urine analysis for alcoholic metabolites. Occup Environ Med
52(11):757-763.
Perbellini, L; Brugnone, F; Gaffuri, E. (1981) Neurotoxic metabolites of "Commercial hexane"
in the urine of shoe factory workers. Clin Toxicol 18(12): 1377-1385.
Perbellini, L; Brugnone, F; Pavan, I. (1980) Identification of the metabolites of n-hexane,
cyclohexane and their isomers in mens urine. Toxicol Appl Pharmacol 53(2):220-229.
3.4.	ELIMINATION
Bartolucci, GB; Perbellini, L; Gori, GP; et al. (1986) Occupational exposure to solvents field
comparison of active and passive samplers and biological monitoring of exposed workers. Ann
Occup Hyg 30(3):295-306.
Gobba, F; Ghittori, S; Imbriani, M; et al. (1997) The urinary excretion of solvents and gases for
the biological monitoring of occupational exposure: a review. Sci Total Environ 199(l-2):3-12.
Kawai, T; Mizunuma, K; Yasugi, T; et al. (1995) Monitoring of exposure to methylpentanes by
diffusive sampling and urine analysis for alcoholic metabolites. Occup Environ Med
52(11):757-763.
Perbellini, L; Brugnone, F; Gaffuri, E. (1981) Neurotoxic metabolites of "Commercial hexane"
in the urine of shoe factory workers. Clin Toxicol 18(12): 1377-1385.
Perbellini, L; Brugnone, F; Pavan, I. (1980) Identification of the metabolites of n-hexane,
cyclohexane and their isomers in mens urine. Toxicol Appl Pharmacol 53(2):220-229.
Phillips, M; Herrera, J; Krishnan, S; et al. (1999) Variation in volatile organic compounds in the
breath of normal humans. J Chromatogr B 729(l-2):75-88.
3.5.	PHYSIOLOGICALLY BASED TOXICOKINETIC MODELS
Perbellini, L; Brugnone, F; Caretta, D; et al. (1985) Partition coefficients of some industrial
aliphatic hydrocarbons (C5-C7) in blood and human tissues. Br J Ind Med 42(3): 162-167.
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4. HAZARD IDENTIFICATION
4.1.	STUDIES IN HUMANS—EPIDEMIOLOGY, CASE REPORTS, CLINICAL
CONTROLS
Abbritti, G; Siracusa, A; Cianchetti, C; et al. (1976) Shoe-makers' polyneuropathy in Italy: The
aetiological problem. Br J Ind Med 33(2):92-99.
Agnesi, R; Valentini, F; Mastrangelo, G. (1997) Risk of spontaneous abortion and maternal
exposure to organic solvents in the shoe industry. Int Arch Occup Environ Health 69(5):311-
316.
Inoue, T; Takeuchi, Y; Takeuchi, S; et al. (1970) Industrial health survey of high incidence of
n-hexane intoxication among vinyl sandal manufacturers. Japanese Journal of Industrial Health
12(3):73-84.
Wayne, LG; Orcutt, JA. (1960) The relative potentials of common organic solvents as precursors
of eye-irritants in urban atmospheres. J Occup Med 2:383-388.
Yamada, S. (1972) Polyneuritis in workers exposed to n-hexane, its cause and symptoms.
Japanese Journal of Industrial Health 9(7):651-659.
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): 1986.
Ono, Y; Takeuchi, Y; Hisanaga, N. (1981) A comparative study on the toxicity of n-hexane and
its isomers on the peripheral nerve. Int Arch Occup Environ Health 48(3):289-294.
4.2.2.	Inhalation
Frontali, N; Amantini, MC; Spagnolo, A; et al. (1979) Poly neuropathy in rats treated with the
different solvent components of the glues used in shoe factories. 3rd European Neuroscience
Meeting, Rome, Italy, Sept. 11-14, 1979. Neurosci Lett Suppl 3:S217.
Frontali, N; Amantini, MC; Spagnolo, A; et al. (1981) Experimental neurotoxicity and urinary
metabolites of the C5-C7 aliphatic hydrocarbons used as glue solvents in shoe manufacture. Clin
Toxicol 18(12): 1357-1367.
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4.3. REPRODUCTIVE/DEVELOPMENTAL STUDIES—ORAL AND INHALATION
Tachi, N; Shimotori, S; Fujise, H; et al. (1994) Fetotoxic effects of exposure to the vapor of
organic solvents from a synthetic adhesive in mice. Bull Environ Contam Toxicol 53(3):471-
478.
4.4.	OTHER ENDPOINT-SPECIFIC STUDIES
4.4.1.	ACUTE AND SHORT TERM STUDIES
Bernard, AM; De Russis, R; Normand, JC; et al. (1989) Evaluation of the subacute
nephrotoxicity of cyclohexane and other industrial solvents in the female sprague-dawley rat.
Toxicol Lett (Amst) 45(2-3):271-280.
Shell Oil Company (1985) Toxicology of hydrocarbons: The skin and eye irritancy of seven
hydrocarbons (external report) with attachments and cover sheet. Submitted under TSCA Section
8d; EPA Document No. 86-870001634; NTIS No. OTS0516215.
4.4.2.	GENOTOXICITY STUDIES
4.4.3.	NEUROTOXICITY STUDIES
Frontali, N; Amantini, MC; Spagnolo, A; et al. (1979) Poly neuropathy in rats treated with the
different solvent components of the glues used in shoe factories. 3rd European Neuroscience
Meeting, Rome, Italy, Sept. 11-14, 1979. Neurosci Lett Suppl(3):S217.
Frontali, N; Amantini, MC; Spagnolo, A; et al. (1981) Experimental neurotoxicity and urinary
metabolites of the c5-c7 aliphatic hydrocarbons used as glue solvents in shoe manufacture. Clin
Toxicol 18(12): 1357-1367.
Ono, Y; Takeuchi, Y; Hisanaga, N. (1981) A comparative study on the toxicity of n-hexane and
its isomers on the peripheral nerve. Int Arch Occup Environ Health 48(3):289-294.
4.4.4.	ENDOCRINE DISRUPTION
4.4.5.	CONTACT SENSITIZATION
4.5.	MECHANISTIC DATA AND OTHER STUDIES IN SUPPORT OF THE MODE OF
ACTION
4.6.	SYNTHESIS OF MAJOR NONCANCER EFFECTS
4.6.1. Oral
4.6.2. Inhalation
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4.6.3. Mode of Action Information
4.7.	EVALUATION OF CARCINOGENICITY
4.7.1.	Summary of Overall Weight-of-Evidence
4.7.2.	Synthesis of Human, Animal, and Other Supporting Evidence
4.7.3.	Mode of Action Information
4.7.2.1.	Hypothesized Mode of Action
4.7.2.2.	Experimental Support for the Hypothesized Mode of Action
4.7.2.3.	Other Possible Modes of Action
4.7.2.4.	Conclusions About the Hypothesized Mode of Action
Support for the hypothesized mode of action in test animals
Relevance of the hypothesized mode of action to humans
Populations or lifestages particularly susceptible to the hypothesized mode of action
4.8.	SUSCEPTIBLE POPULATIONS AND LIFE STAGES
4.8.1.	Possible Childhood Susceptibility
4.8.2.	Possible Gender Differences
4.8.3.	Other
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