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© 1992 Oxford University Press

research-article

Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (OECD): Familiarization Using Cyclophosphamide

SATORU TANAKA*, KUNIO KAWASHIMA{dagger}, KATSUSHI NAITO*, MAKOTO USAMI{dagger}, MASAHIRO NAKADATE*, KATSUMI IMAIDA{ddagger}, MICHIHITO TAKAHASHI{ddagger}, YUZO HAYASHI{ddagger}, YUJI KUROKAWA* and MASUO TOBE§

*Division of Toxicology, National Institute of Hygienic Sciences 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158 {dagger}Division of Pharmacology, National Institute of Hygienic Sciences 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158 {ddagger}Division of Pathology, National Institute of Hygienic Sciences 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158 §Biological Safety Research Center, National Institute of Hygienic Sciences 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158

Received January 23, 1991; accepted June 25, 1991

Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (OECD): Familiarization Using Cyclophosphamide. TANAKA, S., KAWASHIMA, K., NAITO, K., USAMI, M., NAKADATE, M., IMAIDA, K., TAKAHASHI, M., HAYASHI, Y., KUROKAWA, Y., AND TOBE, M. (1992A, Y., AND TOBE, M. (1992). Fundam. Appl. Toxicol. 18, 89–95.

A familiarization study was conducted on the "Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)" proposed by the OECD. Cyclophosphamide (CP) at doses of 6.7, 4.5, 3, 2, and 0 mg/kg body wt was given daily by gavage to groups of 12 male and 12 female Sprague-Dawley rats. As a result, anemia and leukopenia were evident in treated males. The absolute and relative thymus and spleen weights were decreased in treated rats. Histopathologically, atrophy of the thymus, spleen, and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss of fetuses and postnatal death were found in dams given CP. The body weight of pups treated with CP was significantly lowered in a dose-related manner. Thus the results demonstrated most of the known toxicological properties of CP, except the adverse effects on spermatogenesis and fertility. Therefore ReproTox can be considered as a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume.


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