Annotated Reference Outline for the Toxicological Review of 3-Methylpentane (CAS No. 96-14-0) In Support of Summary Information on the Integrated Risk Information System (IRIS)


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ANNOTATED REFERENCE OUTLINE
FOR THE TOXICOLOGICAL REVIEW
OF
3-Methylpentane
(CAS No. 96-14-0)
In Support of Summary Information on the
Integrated Risk Information System (IRIS)
12/22/08
[author: insert current date for this draft or Agency completion date (month and year) iffinal]
NOTICE
This document is a [author: insert Agency Review or external review] 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
Abraham, MH; Ibrahim, A. (2006) Air to fat and blood to fat distribution of volatile organic
compounds and drugs: Linear free energy analyses. European Journal of Medicinal Chemistry
41(12): 1430-1438.
Abraham, MH; Ibrahim, A; Acree, WE, Jr. (2006) Air to brain, blood to brain and plasma to
brain distribution of volatile organic compounds: Linear free energy analyses. European Journal
of Medicinal Chemistry 41(4):494-502.
Abraham, MH; Ibrahim, A; Acree, WE, Jr. (2005) Air to blood distribution of volatile organic
compounds: A linear free energy analysis. Chem Res Toxicol 18:904-911.
ACGIH. (2001) Hexane, isomers other than n-hexane. ACGIH. Documentation of the threshold
limit values and biological exposure indices 3
ACGIH. (2007) Hexane, isomers other than n-hexane. Threshold limit values for chemical
substances and physical agents and biological exposure indices. Cincinnati, OH: American
Conference of Governmental Industrial Hygienists; p. 45.
Carreon, T (2001) Aliphatic hydrocarbons. In: Bingham, E; Cohrssen, B; Powell, CH; et al.;
eds. Patty's toxicology. John Wiley & Sons, Inc.
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).
Galvin, JB; Bond, G. (1999) 3-methylpentane. Cas# 96-14-0. J Toxicol Environ Health A 58(1-
2):93-102.
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.
Spencer, PS; Schaumburg, HH; Sabri, MI; et al. (1980) The enlarging view of hexa carbon neuro
toxicity. CritRev Toxicol 7(4):279-356.
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
Brugnone, F; Perbellini, L; Gaffuri, E; et al. (1980) Biomonitoring of industrial solvent
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exposures in workers' alveolar air. Int Arch Occup Environ Health 47(3):245-261.
Brugnone, F; Perbellini, L; Grigolini, L; et al. (1979) Solvent exposure in a shoe upper factory.
II. Methylcyclopentane, 2-methylpentane, and 3-methylpentane concentration in alveolar and in
environmental air and in blood. Int Arch Occup Environ Health 42(3-4):355-363.
3.2. DISTRIBUTION
Abraham, MH; Ibrahim, A. (2006) Air to fat and blood to fat distribution of volatile organic
compounds and drugs: Linear free energy analyses. European Journal of Medicinal Chemistry
41(12): 1430-1438.
Abraham, MH; Ibrahim, A; Acree, WE, Jr. (2006) Air to brain, blood to brain and plasma to
brain distribution of volatile organic compounds: Linear free energy analyses. European Journal
of Medicinal Chemistry 41(4):494-502.
Abraham, MH; Ibrahim, A; Acree, WE, Jr. (2005) Air to blood distribution of volatile organic
compounds: A linear free energy analysis. Chem Res Toxicol 18:904-911.
Brugnone, F; Perbellini, L; Grigolini, L; et al. (1979) Solvent exposure in a shoe upper factory.
II. Methylcyclopentane, 2-methylpentane, and 3-methylpentane concentration in alveolar and in
environmental air and in blood. Int Arch Occup Environ Health 42(3-4):355-363.
Meulenberg, CJ; Vijverberg, HP. (2000) Empirical relations predicting human and rat tissue: Air
partition coefficients of volatile organic compounds. Toxicol Appl Pharmacol 165(3):206-216.
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.
3.3. METABOLISM
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.
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; Faggionato, G. (1981) Urinary excretion of the metabolites of n-
hexane and its isomers during occupational exposure. Br J Ind Med 38(l):20-26.
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.
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3.4. ELIMINATION
Brugnone, F; Perbellini, L; Gaffuri, E; et al. (1980) Biomonitoring of industrial solvent
exposures in workers' alveolar air. Int Arch Occup Environ Health 47(3):245-261.
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.
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; Faggionato, G. (1981) Urinary excretion of the metabolites of n-
hexane and its isomers during occupational exposure. Br J Ind Med 38(l):20-26.
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. Journal of Chromatography B 729(l-2):75-88.
3.5. PHYSIOLOGICALLY BASED TOXICOKINETIC MODELS
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. International Archives of Occupational and
Environmental Health 69(5):311-316.
4.2.	LESS-THAN-LIFETIME AND CHRONIC STUDIES AND CANCER BIOASSAYS
IN ANIMALS—ORAL AND INHALATION
4.2.1. Oral
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4.2.2. Inhalation
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. Bulletin of Environmental Contamination
and Toxicology 53(3):471-478.
4.4.	OTHER ENDPOINT-SPECIFIC STUDIES
4.4.1.	ACUTE AND SHORT-TERM TOXICITY
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.
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
Grinstaff, MW; Hill, MG; Labinger, JA; et al. (1994) Mechanism of catalytic oxygenation of
alkanes by halogenated iron porphyrins. Science 264(5163): 1311-1313.
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4.6.	SYNTHESIS OF MAJOR NONCANCER EFFECTS
4.6.1.	Oral
4.6.2.	Inhalation
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
4.8.	SUSCEPTIBLE POPULATIONS AND LIFE STAGES
4.8.3. Other
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