Wilson B W, Henderson J D, Kellner T P, McEuen S F, Griffis L C, Lai J C
Department of Environmental Toxicology, University of California, Davis 95616.
Neurotoxicology. 1990 Fall;11(3):483-91.
Reports that near-lethal doses of the pesticide methamidophos (O,S-dimethyl phosphoramidothioate) caused a delayed neurotoxicity (OPIDN) in humans and that another phosphoramidate, isofenphos, caused OPIDN in the hen at high doses, prompted a study of the abilities of acephate (O,S-dimethyl acetylphosphoramidothioate) to inhibit brain acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in vivo. Hens were treated orally with 5-700 mg/kg of acephate, or im with 50-200 micrograms/kg of diisopropyl-fluorophosphate (DFP, positive control) and sacrificed 24 hr later. Brain homogenates were assayed for AChE as an estimate of acute toxicity, for NTE to indicate acephate's potential to cause OPIDN, and for residues of acephate and its metabolite methamidophos. A range finding study confirmed the LD50 level for acephate was approximately 800 mg/kg. Regression analyses indicated an ID50 (a dose that inhibits 50% of activity) for acephate inhibition of AChE of 10 mg/kg and an extrapolated ID50 for inhibition of NTE of 1300 mg/kg, almost twice the LD50. In contrast, ID50 values for DFP were similar for AChE (146 micrograms/kg) and NTE (132 micrograms/kg). Brain methamidophos levels were 10 to 16 percent of the total acephate plus methamidophos brain concentration. The lower the dose of acephate, the higher was the relative percentage of methamidophos. The results show acephate is a more potent inhibitor of AChE than it is of NTE in hens and suggest it would be difficult to administer a single dose of acephate sufficient to cause OPIDN without killing the animal.
有报告称，接近致死剂量的农药甲胺磷（O,S-二甲基硫代磷酰胺）会导致人类迟发性神经毒性（OPIDN），另一种氨基磷酸酯类农药异柳磷在高剂量时会导致母鸡出现OPIDN，这促使人们对乙酰甲胺磷（O,S-二甲基乙酰基硫代磷酰胺）在体内抑制脑乙酰胆碱酯酶（AChE）和神经病变靶酯酶（NTE）的能力进行研究。给母鸡口服5 - 700毫克/千克的乙酰甲胺磷，或肌肉注射50 - 200微克/千克的二异丙基氟磷酸酯（DFP，阳性对照），24小时后将其处死。对脑匀浆进行AChE检测以评估急性毒性，检测NTE以表明乙酰甲胺磷导致OPIDN的可能性，并检测乙酰甲胺磷及其代谢产物甲胺磷的残留量。一项预试验确定乙酰甲胺磷的半数致死剂量（LD50）约为800毫克/千克。回归分析表明，乙酰甲胺磷抑制AChE的半数抑制剂量（ID50）为10毫克/千克，抑制NTE的外推ID50为1300毫克/千克，几乎是LD50的两倍。相比之下，DFP对AChE的ID50值（146微克/千克）和对NTE的ID50值（132微克/千克）相似。脑中的甲胺磷水平占脑内乙酰甲胺磷和甲胺磷总浓度的10%至16%。乙酰甲胺磷的剂量越低，甲胺磷的相对百分比越高。结果表明，在母鸡中，乙酰甲胺磷对AChE的抑制作用比对NTE更强，这表明在不杀死动物的情况下，很难给予足以导致OPIDN的单剂量乙酰甲胺磷。
