Metabolite-based internal doses used in a risk assessment of benzene

Journal Article · Sat Jul 01 04:00:00 EDT 1989 · Environmental Health Perspectives; (USA)

DOI:https://doi.org/10.1289/ehp.8982177· OSTI ID:7150284

Bailer, A J; Hoel, D G ^[1]

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1. National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA)

Risk assessments of benzene have been based upon both human and animal studies. In this paper, metabolite information is used to construct an internal dose (a surrogate of the biologically effective dose) for a given administered dose. The relationship between the administered dose and this internal dose is nonlinear and is well described by a Michaelis-Menten function. The administered doses from the National Toxicology Program's rodent carcinogenicity study of benzene are transformed into internal doses, and these internal doses are used in conjunction with a multistage model to compare previous estimated virtually safe doses (VSD) associated with small added health risks. The ratio of VSD for the administered dose risk assessment to the VSD from the internal dose risk assessment was approximately 1.0 for the F344/N rats and ranged from 2.5 to 5.0 for B6C3F{sub 1} mice in the National Toxicology Program study. For an occupational exposure of 1 ppm, a risk estimate of 0.7 excess cancers/1,000 exposed with an upper bound of 3.5/1,000 was obtained for a total metabolite internal dose risk assessment. Risk estimates based upon internal doses constructed from levels of the toxic metabolites of benzene are also presented. The implication of a dose-rate study of benzene metabolism for risk assessment is discussed, and finally, suggestions for better characterization of the dose-response function for benzene are provided.

• OSTI ID: 7150284
• Journal Information: Environmental Health Perspectives; (USA), Journal Name: Environmental Health Perspectives; (USA) Vol. 82; ISSN 0091-6765; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AROMATICS
BENZENE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CARCINOGENESIS
DOSE RATES
DOSE-RESPONSE RELATIONSHIPS
HYDROCARBONS
KINETICS
METABOLITES
ORGANIC COMPOUNDS
PATHOGENESIS
REACTION KINETICS
RISK ASSESSMENT