Results of Animal Studies Suggest a Nonlinear Dose-Response Relationship for Benzene Effects

• Published in: Environmental health perspectives Vol. 82; pp. 171 - 176
• Main Authors: Parodi, S., Lutz, W. K., Colacci, A., Mazzullo, M., Taningher, M., Grilli, S.
• Format: Journal Article
• Language: English
• Published: United States National Institute of Environmental Health Sciences. National Institutes of Health. Department of Health, Education and Welfare 01-07-1989
• Subjects: 560300 - Chemicals Metabolism & Toxicology; Animals; AROMATICS; BENZENE; Benzene - administration & dosage; Benzene - metabolism; Benzene - toxicity; BIOLOGICAL EFFECTS; CARCINOGENESIS; Carcinogens; DNA adducts; Dosage; Dose response relationship; Dose-Response Relationship, Drug; DOSE-RESPONSE RELATIONSHIPS; EPIDEMIOLOGY; HUMAN POPULATIONS; HYDROCARBONS; Implications of Animal Data to Human Risk Management; Inhalation; Leukemia; Male; Metabolism; Mice; Mutagens; Oblateness; ORGANIC COMPOUNDS; PATHOGENESIS; POPULATIONS; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; Rats; Risk; RISK ASSESSMENT; Rodents
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.8982171

Considering the very large industrial usage of benzene, studies in risk assessment aimed at the evaluation of carcinogenic risk at low levels of exposure are important. Animal data can offer indications about what could happen in humans and provide more diverse information than epidemiological data with respect to dose-response consideration. We have considered experiments investigating metabolism, short-term genotoxicity tests, DNA adduct formation, and carcinogenicity long-term tests. According to the different experiments, a saturation of benzene metabolism and benzene effects in terms of genotoxicity seems evident above 30 to 100 ppm. Below 30 to 60 ppm the initiating effect of benzene seems to be linear for a large interval of dosages, at least judging from DNA adduct formation. Potential lack of a promoting effect of benzene (below 10 ppm) could generate a sublinear response at nontoxic levels of exposure. This possibility was suggested by epidemiological data in humans and is not confirmed or excluded by our observations with animals.