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 in duce an increase in the frequency of micronucleated erythrocytes in mi ce, This study investigated the mutagenicity of benzene at lower conce ntrations, including the current limit for occupational exposure, 1 p. p.m. The frequencies of micronucleated polychromatic erythrocytes (MPC E) in the bone marrow and blood and micronucleated normochromatic eryt hrocytes (MNCE) in the blood of male B6C3F1 mice were measured followi ng inhalation of benzene at 0, 1, 10, 100 or 200 p.p.m. during an 8 we ek exposure period, Only 100 and 200 p.p.m. benzene induced a statisti cally significant increased frequency of micronucleated erythrocytes i n 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 b lood progressively increased to 13.4/1000 (100 p.p.m.) and 32.5/1000 ( 206 p.p.m.) at week 8 as compared with 1.8/1000 for controls, Cytotoxi city of replicating and maturing erythrocytes by 100 and 200 p.p.m. be nzene delayed the accumulation of MNCE in the blood, There was not a s tatistically significant increase in the frequency of micronucleated e rythrocytes,:ls an indicator of mutagenicity, with inhalation of 1 or 10 p.p.m. benzene over an 8 week period, A quadratic curve fit the bon e marrow MPCE data of mice exposed to up to 200 p.p.m. benzene with a high correlation (R(2) = 0.94) and could not be rejected based on lack of fit.