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拟胆碱化合物氯化苄基三甲基铵在雄性大鼠和小鼠体内的毒代动力学

Toxicokinetics of the cholinomimetic compound benzyltrimethylammonium chloride in the male rat and mouse.

作者信息

Sanders J M, Griffin R J, Burka L T, Matthews H B

机构信息

Chemistry Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

出版信息

Xenobiotica. 1995 Mar;25(3):303-13. doi: 10.3109/00498259509061854.

DOI:10.3109/00498259509061854
PMID:7618356
Abstract
  1. Benzyltrimethylammonium chloride (BTMAC)-derived radioactivity was rapidly eliminated from the F344 rat and the B6C3F1 mouse following p.o. administration of 0.63-63 mg/kg of [ring-U-14C] BTMAC. Greater than 90% of the radioactivity was excreted in urine and faeces within 24-h post-dosing. 2. BTMAC was poorly to moderately absorbed from the GI tract following p.o. administration. The percent of total dose absorbed did not exceed either 40% in the rat or 15% in the mouse. 3. Absorption was linear, but limited, over time following dermal administration of 63 mg/kg to the rat. Less than 10% of the total dose was absorbed from the skin within 24 h of BTMAC application. 4. Metabolism of BTMAC was minimal in both the rat and mouse. Toxicity (excessive cholinergic stimulation and mortality) appears to be attributable to the parent compound. 5. The limited absorption and rapid elimination of BTMAC should result in little or no bioaccumulation in tissues following repeated exposure to low levels of this compound. The results suggest that greater human health risks may be associated with acute high level exposure rather than chronic low level exposure.
摘要
  1. 经口给予F344大鼠和B6C3F1小鼠0.63 - 63 mg/kg的[环-U-14C]苄基三甲基氯化铵(BTMAC)后,BTMAC衍生的放射性物质迅速从体内消除。给药后24小时内,超过90%的放射性物质通过尿液和粪便排出。2. 经口给药后,BTMAC从胃肠道的吸收较差至中等。大鼠吸收的总剂量百分比不超过40%,小鼠不超过15%。3. 给大鼠经皮给予63 mg/kg的BTMAC后,随着时间推移,吸收呈线性但有限。在应用BTMAC后24小时内,从皮肤吸收的总剂量不到10%。4. BTMAC在大鼠和小鼠体内的代谢都极少。毒性(过度胆碱能刺激和死亡)似乎归因于母体化合物。5. BTMAC吸收有限且消除迅速,反复接触低水平该化合物后,组织中几乎不会或不会发生生物蓄积。结果表明,对人类健康的更大风险可能与急性高剂量暴露有关,而非慢性低剂量暴露。

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