The carcinogenicity of discontinuous inhaled benzene exposures in CD-1 and C57Bl/6 mice

Abstract

Groups of male C57Bl and CD-1 mice were exposed to benzene via inhalation using two different exposure protocols. One protocol consisted of repetitive week-long exposures to 300 ppm benzene (6 h/d×5 d/wk) interrupted by 2 weeks of non-exposure. The exposure pattern (1 week of exposure followed by 2 weeks of non-exposure) was continued until the death of the last exposed animal. The second protocol consisted of exposures to 1200 ppm benzene (6 h/d×5 d/wk) for 10 weeks. Exposures were then terminated and the animals allowed to live out their lives. For each protocol, appropriate age-matched control mice received comparable exposures to filtered, conditioned air. The discontinuous exposure patterns mimic the patterns of exposure often encountered in the workplace and, in addition, prolong the survival of exposed animals so as to maximize potential tumorigenic responses. Both exposure protocols were markedly hematotoxic to both mouse strains as measured by peripheral blood counts. Both strains of mice responded to the intermittent 300 ppm benzene exposures with elevated incidences of malignant tumors. Particularly noteworthy was a 35% incidence of zymbal gland tumors in the C57Bl mice. In contrast, only the CD−1 mice responded to the 1200 ppm benzene exposures delivered over 10 weeks with elevated tumor incidences. A 46% incidence of lung adenoma was particularly striking in these mice. Neither of the benzene exposure protocols induced elevated incidences of leukemia/lymphoma in either strain. These studies demonstrate that discontinuous exposures to benzene are tumorigenic and that a lifetime exposure to benzene, even if delivered at a lower concentration and in an intermittent exposure pattern, is more tumorigenic than a short-term exposure to benzene.