TOXICOLOGY AND APPLIED PHARMACOLOGY 54, 323-331 (1980) The Inhalation Toxicology of Benzene: Incidence of Hematopoietic Neoplasms and Hematotoxicity in AKWJ and C57BL/6J Mice CARROLL A. SNYDER,BERNARD D. GOLDSTEIN,ARTHUR R. SELLAKUMAR, ISABEL BROMBERG, SIDNEY LASKIN,'AND ROY E. ALBERT New York University, lnstittcte of Environmental Medicine, 550 First Avenue, New York, New York 10016 Received September 25, 1979; accepted February 26, 1980 The Inhalation Toxicology of Benzene: Incidence of Hematopoietic Neoplasms and Hematotoxicity in AKR/J and C57BL/6J Mice. SNYDER, C. A., GOLDSTEIN, B. D., SEL- LAKUMAR, A. R., BROMBERG, I., LASKIN, S., AND ALBERT, R. E. (1980). Toxicol. Appl. Pharmacol. 54, 323-331. AKR/J mice and C57BW6J mice were given lifetime exposures to 100 and 300 ppm benzene, respectively. Peripheral blood cell counts were obtained bi- weekly throughout the exposures. Anemia and lymphocytopenia were produced in ben- zene-exposed AKR mice. Twenty percent of the exposed AKR mice developed bone mar- row hypoplasia, compared to 2% for the controls. The benzene exposures did not alter the incidence or induction time of the viral-induced lymphomas commonly seen in AKR mice. In C57BL mice, exposure to benzene produced anemia, lymphocytopenia, and neutrophilia accompanied by a left shift. Thirteen (33%) of the exposed C57BL mice developed bone marrow hyperplasia and in four of these mice, hyperplasia was essentially limited to granulo- poietic elements. None of the control C57BL mice developed bone marrow hyperplasia. In benzene-exposed C57BL mice there was a significant increase in the incidence of hemato- poietic neoplasms including six cases (15%) of thymic lymphoma. Although two control mice (5%) died with lymphoma neither of these tumors involved the thymus. Thymic lymphoma is rare in C57BL mice but can be produced by ionizing radiation and chemical carcinogens Human exposure to benzene has been asso- tory (Snyder et al., 1978a) there appear to ciated with pancytopenia and its variants be no reports of the experimental produc- (Aksoy et al., 1971, 1972, 1976; Mallory tion of benzene-induced myelogenous leu- et al., 1939; Pollini et al., 1969; Saita and kemia. Inhalation studies have, for the most Sbertoli, 1954) and acute myelogenous part, been of short duration and/or have in- leukemia and its variants (Aksoy et al., volved acute or subacute exposure levels 1976; Saita and Vigliani, 1962; Tareeff et al., (Boje et al., 1970; Deichmann et al., 1963; 1963; Vigliani and Saita, 1964). The cyto- Jenkins et al., 1970; Nau et al., 1966; Uyeki penic effects of benzene exposure have been et al., 1977). In addition, a great deal of readily reproduced in animals, most often previous work has produced confusing and by parenteral injection (Gerarde and Ahl- often contradictory results regarding both Strom, 1966; Latta and Davis, 1941; Minai, the cytopenic and proliferative effects of 1967; Selling, 1916; Weiskotten et al., 1916). benzene exposure (Laskin and Gold- Except for work performed in this labora- stein, 1977). 1 Deceased. The purpose of our studies is to acquire hematological dose-response information 323 0041~008x180/080323-09$02.00/O Copyright 0 1980 by Academic Press, Inc. All rights of reproduction in any form reserved.