Results of animal studies suggest a nonlinear dose-response relationship for benzene effects.

Abstract

Considering the very large industrial usage of benzene, studies in risk assessment aimed at the evaluation of carcinogenic risk at low Ievels 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 doseresponse 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 ofbenzene seems tobe linear fora large intervaJ ofdosages, at least judging from DNA adduct formation. Potentiallack of a promoting effect of benzene (below 10 ppm) could generate a sublinear response at nontox.ic levels of ex.posure. This possibility was suggested by epidemiological data in humans and is not confirmed or excluded by our observations with animals.

Benzene adducts with rat nucleic acids and proteins: dose-response relationship after treatment in vivo.

“…The relationship between adduct formation to DNA, saturation of benzene metabolism at the upper doses (in RNA, and protein of the assayed organs and benzenethe 10-100 ppm range), as previously discussed by Grilli administered dose stayed linear within a wide range of et al (2) and confirmed by Parodi et al (11). The satura-dosages less than 48.6 mg/kg.…”