Benzene-Induced Hematotoxicity and Myelotoxicity by Short-Term Repeated Oral Administration in Mice

초록

Exposure dose of benzene has been postulated to be critical to induce hemopoietic malignancies. By long-term inhalation of benzene, 300 ppm has been shown to be the dose that induces high frequency of leukemia with the least animal mortality in the mouse. With regard to the benzene studies, determination of the oral dose that will be corresponding to the critical inhalation dose could be important to design the experimental protocol based on oral administration. Based on the background data such as the respiratory volume, absorption factor, and so on, we, therefore, calculated a potential oral dose that is expected to be corresponding to 300 ppm of inhalation dose. The determined oral dose was 150 mg/kg B.W. We then evaluated, using C57BL/6 mice, the toxic effects of benzene on the peripheral blood and the bone marrow (BM) by oral administration of the selected dose once a day for 1 and 2 weeks. Leukocyte, red blood cell number and BM cellularity were respectively decreased to 47.8%, 72.3% and 66.7% of the respective control level by 1-week oral administration of benzene, and to 30.8%, 60.2% and 80.2% by 2-week oral administration. Changes in the leukocyte numbers were mainly due to the marked decrease of lymphocytes. According to the results, the changes of the parameters examined were generally corresponding to the change levels by the 2-week inhalation. In conclusion, the selected dose, 150 mg/kg B.W., was a reliable dose corresponding to the 300 ppm benzene inhalation, which was verified by in vivo mouse study.

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