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EC number: 218-747-8
CAS number: 2224-33-1
Methylethyl ketoxime was tested for reproductive toxicity in
two-generation study with CD (Sprague-Dawley) rats according to EPA OTS
798.4700. Thirty rats per sex and per dose (F0) were administered MEKO
in water by gavage at 0 (control), 10, 100 and 200 mg/kg bw/day, 5
days/week for 10 weeks with vaginal cytology evaluation (VCE) of F0
females during the last 3 weeks of the prebreed period. Animals were
mated within groups for 3 weeks with dosing during mating, gestation,
and lactation for 7 days/week. F0 parents and F1 weanlings, 10/sex/dose,
were necropsied (after a 2-week postwean VCE in F0 females) with
hematologic evaluation (including methemoglobin) and histology of adult
livers, spleens, and reproductive organs. F1 weanlings, 30/sex/dose,
were dosed for 11 weeks and mated as described above. Because of poor
reproductive performance, not treatment related, F1 animals with no F2a
litters were rebred to produce F2b litters. F1 parents and F2a
weanlings, 10/sex/dose, were necropsied and evaluated as described
above. Inguinal mammary glands were examined histologically from all
nonselected F1 and F2 (a and b) female weanlings. Adult toxicity was
observed in both generations and both sexes at all doses.
Treatment-related parental deaths occurred at 200 mg/kg/day. At 100 and
200 mg/kg/day, parents exhibited dose-related reduced body weights and
weight 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 was
no evidence of reproductive organ or mammary gland pathology or of
reproductive or postnatal toxicity at any dose tested. Therefore, the
NOAEL for reproductive and postnatal toxicity was at least 200 mg/kg/day
for rats in this study.
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