TOXICITY OF CHEMOSTERILANTS

(I) TOXICITY OF ALKYLATING AGENT "METEPA" TO RATS AND MICE

Abstract

The toxicity of a chemosterilant, metepa, tris [1-(2-methyl) aziridinyl] phosphine oxide, to rats and mice was studied.
1) The acute oral LD₅₀ value of metepa was 277 mg/kg for rats, compared with 292 mg/kg for mice. The dermal toxicity was 375 mg/kg for mice.
2) In the subacute toxicity test on male rats, given orally metepa totalling 480 mg/kg in 8 days, metepa showed the typical properties as an alkylating agent. It caus-ed the profound effects against the proliferating tissues such as the testes and the bone marrow. The spleen was also affected. Further, the growth suppression and the reduction of blood cell counts were noticed.
3) Daily oral administration (2.5-20 mg/kg/day) of metepa to rats for 84 days caused the growth suppression, the reduction of white blood cell counts and the testi-cular atrophy at higher levels. Severe degeneration of spermatogenic cells and occasio-nally multinucleated giant cells were observed microscopically. Although female rats appeared in general less sensitive to metepa than males, the histopathologic examination revealed the lesions in the ovaries even at a level of 5 mg/kg/day. No-effect level for three-month test appeared to be 2.5 mg/kg/day for male rats and was not fixed for females by the present experiment.