Benzene-induced micronuclei in erythrocytes: an inhalation concentration-response study in B6C3F1 mice.

High concentrations (300-1000 p.p.m.) of benzene have been shown to induce an increase in the frequency of micronucleated erythrocytes in mice. This study investigated the mutagenicity of benzene at lower concentrations, including the current limit for occupational exposure, 1 p.p.m. The frequencies of micronucleated polychromatic erythrocytes (MPCE) in the bone marrow and blood and micronucleated normochromatic erythrocytes (MNCE) in the blood of male B6C3F1 mice were measured following inhalation of benzene at 0, 1, 10, 100 or 200 p.p.m. during an 8 week exposure period. Only 100 and 200 p.p.m. benzene induced a statistically significant increased frequency of micronucleated erythrocytes in the bone marrow and blood. The frequency of MPCE plateaued at week 2 with 43/1000 (100 p.p.m.) and 86/1000 (200 p.p.m.) in the bone marrow as compared with 10/1000 for controls. The frequency of MNCE in the blood progressively increased to 13.4/1000 (100 p.p.m.) and 32.5/1000 (200 p.p.m.) at week 8 as compared with 1.8/1000 for controls. Cytotoxicity of replicating and maturing erythrocytes by 100 and 200 p.p.m. benzene delayed the accumulation of MNCE in the blood. There was not a statistically significant increase in the frequency of micronucleated erythrocytes, as an indicator of mutagenicity, with inhalation of 1 or 10 p.p.m. benzene over an 8 week period. A quadratic curve fit the bone marrow MPCE data of mice exposed to up to 200 p.p.m. benzene with a high correlation (R2 = 0.94) and could not be rejected based on lack of fit.