Soliman S A, Svendsgaard D, Farmer J D, Curley A, Durham W F
Toxicol Appl Pharmacol. 1983 Jul;69(3):417-31. doi: 10.1016/0041-008x(83)90265-x.
The delayed neurotoxic effects of tri-o-cresyl-phosphate (TOCP), O-methyl-O-(4-bromo-2,5-dichlorophenyl) phenylphosphonothioate (leptophos), and O-ethyl O-(4-nitrophenyl) phenylphosphonothioate (EPN) at 5, 5, and 1 mg/kg/day, respectively, on male sheep were studied during 6 months of daily oral treatment under field conditions. A vehicle-control group of sheep given corn oil (0.1 ml/kg/day) only was used for comparison. All sheep were killed 24 h after the 180th daily treatment. Blood, brain, spinal cord, and sciatic nerve tissues were taken for histological and/or biochemical examinations. The results indicated that leptophos induced severe ataxia and paralysis in sheep following about 4 months of treatment. TOCP produced either mild ataxia or lameness in two of four sheep during the last week of experiment. On the other hand, none of the EPN-treated sheep showed clinical signs of neurotoxicity during the course of the experiment at the dosage tested. These clinical results were supported by histological findings and also by biochemical results with neurotoxic esterase (NTE) measurements. In the case of leptophos-treated sheep, numerous prominent degenerative lesions of axons were observed in spinal cords and brains. Similar but somewhat less numerous lesions were noted in sheep treated with TOCP. No histological changes were observed in similar tissues taken from EPN-treated sheep. The results also indicated that, for chronic exposure to these neurotoxic organophosphorus compounds in sheep, a threshold in excess of 60-70% prolonged inhibition of brain NTE, or 50-60% inhibition of spinal cord NTE must be exceeded to initiate clinical and/or histological neurotoxic effects.
在野外条件下，对雄性绵羊分别每日口服5、5和1毫克/千克的磷酸三邻甲苯酯（TOCP）、O-甲基-O-（4-溴-2,5-二氯苯基）苯硫代磷酸酯（倍硫磷）和O-乙基-O-（4-硝基苯基）苯硫代磷酸酯（EPN），研究其延迟性神经毒性作用，为期6个月。设立仅给予玉米油（0.1毫升/千克/天）的溶剂对照组进行比较。在第180次每日给药后24小时处死所有绵羊。采集血液、脑、脊髓和坐骨神经组织进行组织学和/或生化检查。结果表明，倍硫磷在治疗约4个月后导致绵羊出现严重共济失调和麻痹。TOCP在实验最后一周，使四只绵羊中的两只出现轻度共济失调或跛行。另一方面，在实验过程中，接受EPN治疗的绵羊在测试剂量下均未表现出神经毒性的临床症状。这些临床结果得到了组织学发现以及神经毒性酯酶（NTE）测量的生化结果的支持。在倍硫磷治疗的绵羊中，脊髓和脑中观察到大量明显的轴突退行性病变。在接受TOCP治疗的绵羊中也观察到类似但数量略少的病变。在接受EPN治疗的绵羊的类似组织中未观察到组织学变化。结果还表明，对于绵羊长期接触这些神经毒性有机磷化合物，要引发临床和/或组织学神经毒性作用，必须超过脑NTE延长抑制超过60 - 70%或脊髓NTE抑制50 - 60%的阈值。
