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- W2073854735 abstract "5-(α,α,α-Trifluoro-m-tolyoxymethyl)-2-oxazolidinethione, or U-11,634, effectively inhibits pregnancy in rats at multiple oral or subcutaneous doses of 2.5 mg or a single subcutaneous dose of 5 mg. A toxicologic evaluation of this compound was performed at multiples of this therapeutic dose. The acute LD50 studies were done intraperitoneally in the mouse (451 mg/kg) and orally in the rat (524 mg/kg). Significant signs of toxicity were not observed in swine photosensitization studies or in rat fetal studies. Rats tolerated an oral dose of 10 mg/kg/day for one month without significant untoward effect; however, higher levels (30 and 100 mg/kg/day) produced various effects, the most significant of which was an antithyroid effect. When U-11,634 was given orally to dogs for one month, it was slightly toxic at 30 mg/kg/day, moderately toxic at 100 mg/kg, and very toxic at 300 mg/kg/day. The signs of toxicity consisted of antithyroid effects in all the treated dogs, and toxic hepatitis in some of the dogs at the higher dosages. Additional studies in dogs and rats at 100 mg/kg/day indicated that the antithyroid effects in both species, and elevated bromsulfalein retention and alkaline phosphatase values in dogs reversed following cessation of treatment. The increase in monocytes in the blood and the bone marrow changes need further study. The antifertility effects of U-11,634 in rats were evaluated in the presence of exogenous thyroxine and iodine. This supplemental treatment did not change the pregnancy-inhibiting activity of U-11,634 nor did it inhibit pregnancy in the absence of U-11,634. The effect on early pregnancy of subacute treatment with known antithyroid agents was assessed. No inhibition of pregnancy was observed following their administration from proestrus through day 6 of pregnancy. On the basis of these observations and available literature reports, it is concluded that the antithyroid effect of U-11,634 does not account for the compound's antifertility efficacy." @default.
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- W2073854735 date "1967-03-01" @default.
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- W2073854735 title "Toxicologic and interrelated studies with an oxazolidinethione contraceptive" @default.
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- W2073854735 doi "https://doi.org/10.1016/0041-008x(67)90114-7" @default.
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