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EC number: 218-747-8
CAS number: 2224-33-1
Preliminary Dose Range-Finding Study results:
All rats survived treatment. Pregnancy was found to be 100% except for
83.3% (5/6) at the 100 mg/kg level. No treatment-related changes were
observed at 25, 100, and 200 mg/kg. Clinical signs of toxicity were at
the 400 mg/kg level. These findings included wobbly gait, weak body
tone, and general decreased responsiveness. The signs were transient and
not observed prior to MEKO administration on the following day. Mean
body weights and body weight gains in dams were generally comparable
between the control, 25, 100, and 200 mg/kg levels. Slight body weight
losses occurred at 400 mg/kg during gestation days 6–9. Dose-dependent
increases in the percentage of reticulocytes and methemoglobin levels
occurred in dams at all dose levels tested. The increases in
reticulocytes were noted in dams at 200 and 400 mg/kg on gestation days
7, 12, 16, and 20 and at 25 mg/kg and 100 mg/kg on gestation days 12,
16, and 20. The increases in methemoglobin occurred at each interval
tested at 25, 100, 200, and 400 mg/kg. At study termination, the
methemoglobin levels were considerably lower than at the end of the
treatment period indicating recovery was taking place. Necropsy findings
included enlarged and blackish-purple spleens at 100, 200, and 400
mg/kg. Spleen adhesions were also observed in one animal at 400 mg/kg.
All dams in the 25 mg/kg group were normal internally. All gestational
parameters evaluated during Cesarean section observations including
viable fetuses, early and late resorptions, fetal sex ratios, gravid
uterus weights and fetal body weights were comparable between the
control and treatment groups. No fetal external malformations or
developmental variations were observed at any group.
A Prenatal Developmental Toxicity Test was performed on methyl ethyl
ketoxime in Sprague-Dawley rats according to EPA OTS 798.4900 Following
preliminary dose range finding studies, groups of 25 pregnant rats were
dosed by gavage with aqueous solutions of methyl ethyl ketoxime at 0
(control), 60, 200, or 600 mg/kg on gestation days 6–15. Several
parameters were periodically observed, such as body weight, feed
consumption, clinical pathology, ovaries and uterine content and fetal
morphology. Dose dependent clinical signs of maternal toxicity including
reduced body weight gains were noted at 200 and 600 mg/kg. At 60 mg/kg
and above enlarged spleens were observed at necropsy. The preliminary
study found methemoglobin formation and reticulocytosis indicative of
anemia at these dose levels. No treatment-related gestational effects,
malformations or developmental variations were observed in the rats.
MEKO was not considered to have produced any treatment-related
gestational effects and therefore, the NOAEL for developmental toxicity
of methyl ethyl ketoxime was determined to be > 600 mg/kg bw/day in rats
under test conditions.
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