REPRODUCTIVE TOXICITY EVALUATION OF METHYLETHYL KETOXIME BY GAVAGE INCD RATS

Methylethyl ketoxime (CAS No. 96-29-7; MEKO; 2-butanone oxime), an ant ioxidant agent used in paints, resins, and adhesives, was tested for r eproductive toxicity in a two-generation study with CD (Sprague-Dawley ) rats. Thirty-eight-week-old rats/sex/group (F0) were administered ME KO in water, by gavage, at 0, 10, 100, or 200 mg/kg/day (at a dosing v olume of 2 ml/kg), 5 days/week for 10 weeks with vaginal cytology eval uation (VCE) of F0 females during the last 3 weeks of the prebreed per iod. Animals were mated within groups for 3 weeks with dosing during m ating, gestation, and lactation for 7 days/week. F0 parents and F1 wea nlings, 10/sex/dose, were necropsied (after a 2-week postwean VCE in F 0 females) with hematologic evaluation (including methemoglobin) and h istology of adult livers, spleens, and reproductive organs. F1 weanlin gs, 30/sex/dose, were dosed for 11 weeks and mated as described above. Because of poor reproductive performance, not treatment related, F1 a nimals with no F2a litters were rebred to produce F2b litters. F1 pare nts and F2a weanlings, 10/sex/dose, were necropsied and evaluated as d escribed above. Inguinal mammary glands were examined histologically f rom all nonselected F1 and F2 (a and b) female weanlings. Adult toxici ty was observed in both generations and both sexes at all doses. Treat ment-related parental deaths occurred at 200 mg/kg/day. At 100 and 200 mg/kg/day, parents exhibited dose-related reduced body weights and we ight gains, reduced feed consumption, clinical signs of toxicity, and anemia with concomitant extramedullary hematopoiesis and hemosiderosis in livers and spleens (and increased spleen weights). At 10 mg/kg/day , only adult liver and spleen histologic effects were present. There w as no evidence of reproductive organ or mammary gland pathology or of reproductive or postnatal toxicity at any dose tested. There was no ad ult ''no observable adverse effect level'' (NOAEL) established; the NO AEL for reproductive and postnatal toxicity was at least 200 mg/kg/day for rats in this study. (C) 1996 Society of Toxicology