Toxicology & Environmental Research and Consulting, The Dow Chemical Company, 1803 Building, Midland, MI 48674, USA.
Regul Toxicol Pharmacol. 2012 Jul;63(2):209-24. doi: 10.1016/j.yrtph.2012.03.015. Epub 2012 Apr 7.
The effect of age or dose regimen on cholinesterase inhibition (ChEI) from chlorpyrifos (CPF) or CPF-oxon (CPFO) was studied in Crl:CD(SD) rats. Rats were exposed to CPF by gavage in corn oil, rat milk (pups), or in the diet (adults) or to CPFO by gavage in corn oil. Blood CPF/CPFO levels were measured. With acute exposure, ChEI NOELs were 2 mg/kg CPF for brain and 0.5 mg/kg CPF for red blood cells (RBCs) in both age groups. In pups, ChEI and blood CPF levels were similar using either milk or corn oil vehicles. Compared to gavage, adults given dietary CPF (12 h exposure) had greater RBC ChEI, but lower brain ChEI at corresponding CPF doses, indicating an effect of dose rate. With repeated CPF exposures, ChEI NOELs were the same across ages (0.5 and 0.1 mg/kg/day for brain and RBCs, respectively). With CPFO dosing, the ChEI NOELs were 0.1 mg/kg (acute) and 0.01 mg/kg/day (repeated doses) for RBCs with no ChEI in brain at CPFO doses up to 0.5 (pup) or 10 mg/kg (adult) for acute dosing or 0.5 mg/kg/day for both ages with repeat dosing. Thus, there were no age-dependent differences in CPF ChEI via acute or repeated exposures. Pups had less ChEI than adults at comparable blood CPF levels. Oral CPFO resulted in substantial RBC ChEI, but no brain ChEI, indicating no CPFO systemic bioavailability to peripheral tissues.
研究了年龄或剂量方案对毒死蜱（CPF）或其氧代物（CPFO）所致胆碱酯酶抑制（ChEI）的影响。大鼠经灌胃染毒，染毒物分别为玉米油中的 CPF、乳鼠奶（幼仔）中的 CPF、成鼠饲料中的 CPF 或玉米油中的 CPFO。检测血中 CPF/CPFO 水平。急性染毒时，两组幼仔和成年大鼠脑和 RBC 中 ChEI 的无作用水平（NOEL）分别为 2mg/kg CPF 和 0.5mg/kg CPF。幼仔经奶或玉米油载体染毒，其 ChEI 和血 CPF 水平相似。与灌胃染毒相比，经饲染毒（12 小时染毒）的成鼠，其 RBC 中 ChEI 更高，但脑 ChEI 更低，表明存在剂量率效应。反复染毒时，各年龄组的 ChEI NOEL 相同（脑和 RBC 分别为 0.5 和 0.1mg/kg/天）。CPFO 染毒时，RBC 中 ChEI 的 NOEL 为 0.1mg/kg（急性染毒）和 0.01mg/kg/天（反复染毒），脑内 ChEI 未检出，染毒剂量高达 0.5（幼仔）或 10mg/kg（成鼠）时，急性染毒，或反复染毒时，0.5mg/kg/天，各年龄组的 ChEI 均无变化。因此，急性或反复染毒时，CPF 所致 ChEI 无年龄相关性差异。与成鼠相比，幼仔血 CPF 水平相同时，ChEI 更低。口服 CPFO 可引起 RBC 中 ChEI 显著升高，但脑内 ChEI 未检出，表明 CPFO 无系统生物利用度，不能到达外周组织。
