Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Data waiving:
other justification
Justification for data waiving:
other:

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Toxicological profile for n-hexane.
Author:
ATSDR
Year:
1999
Bibliographic source:
U.S. Department of Health and Human Services. Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA.
Reference Type:
review article or handbook
Title:
A review of the bioavailability of petroleum constituents.
Author:
Brainard J, Beck B
Year:
1993
Bibliographic source:
Hydrocarbon Contaminated Soils and Ground Water, Lewis Publishers 481-517.
Reference Type:
publication
Title:
Uptake of 19 hydrocarbon vapors inhaled by F344 rats.
Author:
Dahl A, Damon E, Mauderly J, Rothenberg S, Seiler F, McClellan R
Year:
1988
Bibliographic source:
Fundamental and Applied Toxicology 10:262-269.
Reference Type:
publication
Title:
Development of a physiologically based pharmacokinetic model for volatile fractions of gasoline using a chemical lumping analysis.
Author:
Dennison, J., Andersen, M., Clewell, H., and Yang, R
Year:
2004
Bibliographic source:
Environmental Science and Technology 38:5674-5681.
Reference Type:
publication
Title:
Characterization of the pharmacokinetics of gasoline using PBPK modeling with a complex chemicals modeling approach.
Author:
Dennison, J., Andersen, M., and Yang, R.
Year:
2003
Bibliographic source:
Inhalation Toxicology 15:961-986.
Reference Type:
publication
Title:
The toxicology of n-pentane
Author:
McKee R, Frank E, Heath J, Owen D, Przygoda R, Trimmer G, Whitman F
Year:
1998
Bibliographic source:
Journal of Applied Toxicology 18:431-442.
Reference Type:
publication
Title:
Adjustment of occupational exposure levels for unusual work schedules
Author:
Verma D
Year:
2000
Bibliographic source:
American Industrial Hygiene Association Journal 61:367-374.

Materials and methods

Results and discussion

Applicant's summary and conclusion

Executive summary:

Absorption

Inhalation: Absorption of the constituents of gasoline tends to increase with increasing molecular weight with straight chain molecules being more highly absorbed than branched isomers and aromatic molecules being more highly absorbed than paraffins (Dahl et al., 1988). Thus, butane and most of the pentane isomers are very poorly absorbed and if absorbed are rapidly exhaled. Absorption of isobutene was estimated as 14% in humans and 5.4% in rats (Galvin and Bond, 1999a). Rodent data indicate that approximately 5% of neopentane, 9% of isopentane and 19% of n-pentane are absorbed (Galvin and Panson, 1999a; Galvin and Maraschi, 1999a; Galvin and Marashi, 1999b). Approximately 35% of inhaled cyclopentane is absorbed. Approximately 20% of inhaled n-hexane is absorbed (ATSDR, 1999). Absorption is estimated as 23-78% for cyclohexane, 50% for benzene, 50% and for toluene. As an overall approximation it would be reasonable to assume that in both humans and animals, approximately 15% of the C3 to C5 constituents, 25% of the hexanes and approximately 50% of the remainder would be absorbed. Higher molecular weight constituents are not expected to contribute substantially to inhalation exposure (Mckee et al., 2000). 

 

Oral: It would be reasonable to assume that approximately 100% of ingested gasoline and naphtha constituents would be absorbed.

Dermal: The percutaneous absorption of gasoline and naphtha constituents is difficult to assess because of the volatile nature of these substances. Material applied to the skin typically vaporizes quickly with limited absorption. Conversely when material is applied to the skin under conditions that prevent evaporation, such as the use of occluded patches, substantially higher levels of absorption have been measured. Using benzene as an example, as summarized by Brainard and Beck (1993), in dermal penetration studies that utilized occlusive patches, benzene absorption approached 100%, but if the benzene was simply allowed to evaporate from the skin, the fraction absorbed was closer to 1%. 

 

Metabolism

Regardless of the route by which they were absorbed, gasoline and naphtha constituents are rapidly metabolized and eliminated. The alphatic constituents are generally metabolized to the corresponding alcohols (Galvin and Marashi, 1999a; 1999b; 1999c; Galvin and Panson, 1999a; 1999b; 1999c; Galvin and Bond, 1999b). The metabolism of benzene is more complex, beginning with the formation of benzene oxide. There are several possible succeeding pathways leading to phenyl mercapturic acid, phenol, catechol or muconaldehyde. Higher aromatics are primarily metabolized by side chain oxidation to benzyl alcohols and ultimately hippuric acids. 

 

Distribution

All of the gasoline and naphtha constituents are hydrophobic, indicating a higher affinity for adipose than other tissues, although there are differences in distribution of the individual constituents depending on their specific physical and chemical properties. None of the constituents is considered to be an accumulative substance.

 

Excretion

The lower molecular weight gasoline and naphtha constituents are primarily excreted by exhalation, either in their metabolized or un-metabolized forms (Galvin and Bond, 1999a). Overall biological half times for these constituents are typically measured in minutes (McKee et al., 1998). Cyclohexane is also primarily eliminated, unchanged in the exhaled air. Metabolites of other constituents are primarily excreted as urinary metabolites with biological half times on the order of 3-5 hours based on blood measurements and up to 12 hours based on urinary excretion data (Verma, 2000). 

Additional references on gasoline constituents:

Galvin J, Bond G (1999a). Isobutane, Journal of Toxicology and Environmental Health Part A 58:3-22.

        Galvin J, Bond G (1999b). 2-Methylpentane, Journal of Toxicology and Environmental Health Part A 58:81-92.

        Galvin J, Bond G (1999c). 3-Methylpentane, Journal of Toxicology and Environmental Health Part A 58:93-102.

        Galvin J, Marashi F (1999a). 2-Methylbutane (isopentane). Journal of Toxicology and Environmental Health Part A 58:23-34.

Galvin J, Marashi F (1999b). n-Pentane, Journal of Toxicology and Environmental Health Part A 58:35-56.

        Galvin J, Marashi F (1999c). Cyclopentane, Journal of Toxicology and Environmental Health Part A 58:57-74

        Galvin J, Panson R (1999a). Neopentane, Journal of Toxicology and Environmental Health Part A 58:75-80.

        Galvin J, Panson R (1999b). 2,2-Dimethylbutane, Journal of Toxicology and Environmental Health Part A 58:103-110.

Galvin J, Panson R (1999c). 2,3-Dimethylbutane, Journal of Toxicology and Environmental Health Part A 58: 111-118.