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Skin Absorption and Metabolism/Toxicokinetic Study of 14C-2-Nitropropane in Female Rhesus Monkeys with Cover Letter dated 04/26/94

机译:女性恒河猴14C-2-硝基丙烷的皮肤吸收和代谢/毒代动力学研究,封面信件日期为1994年4月26日

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The study was designed to provide information on the absorption of the test material when applied dermally to female adult rhesus monkeys. After shaving the backs of two female rhesus monkeys and marking a 20 cm2 area as test site by tattooing, a single dermal dose (i.e., 300 ul ether/alcohol solution containing 4.9% 14C-2-nitropropane) was applied on the intact skin by means of a disposable plastic syringe equipped with a feeding needle to guarantee a smooth application. Thereafter, the test site was covered with an occlusive plastic foil patch and taped air tight over the test site. Twelve hours after dose application the patch was removed and the skin was wiped with soap and acetone swabs to remove remaining test material. The swab and the patch were extracted with acetone and alcohol respectively. The extracts were assayed for radioactivity. Thereafter, the swabs were combusted to 14CO2 and H20 and assayed for radioactivity. Blood samples, urine and feces were collected for 72 hours after dosing and assayed for radioactivity. Seventy-two hours after dose application, the test site and two adjacent triangles (approximately 1.13 cm2) on both ends of the test site were excised. Skin and subcutaneous fat/tissue were assayed for radioactivity. The skin samples (treated and untreated) were also examined histologically. Neither animal showed any signs of toxicity. Feed and water consumption was normal. Urine output of both monkeys was partly very low or non-existent during the first 12-hour post-dose. After 12 hours the output normalized. The feces output in general was very low. PH0143 had no feces between 0 and 12 hours post-dose. PH0141 had no feces between 8 and 24 hours post-dose and did not at 48 hours post-dose. The body weight remained within 5% of the starting weight. Histological examination of the skin samples did not show any signs of skin damage or irritation. All percentages given in the summary are the average (when not otherwise marked) of the two animals. The terms excretion, percentage, doses, etc. refer to the radioactivity of the corresponding samples.

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