Albers James W, Garabrant David H, Mattsson Joel L, Burns Carol J, Cohen Sarah S, Sima Cami, Garrison Richard P, Richardson Rudy J, Berent Stanley
Department of Neurology, University of Michigan Health System, Ann Arbor, Michigan 48109-0032, USA.
Toxicol Sci. 2007 May;97(1):196-204. doi: 10.1093/toxsci/kfm028. Epub 2007 Feb 25.
We performed nerve conduction studies (NCSs) on 113 chemical workers, many of whom had occupational exposure to the organophosphorus insecticide chlorpyrifos (O,O-diethyl-O-[3,5,6-trichloro-2-pyridyl]-phosphorothioate), to identify dose effects of subclinical neuropathy. In this masked longitudinal study, we estimated historic and interim chlorpyrifos exposures and measured excretion of 3,5,6 trichloro-2-pyridinol (TCP), a chlorpyrifos metabolite. TCP excretion among exposed workers suggested an estimated daily chlorpyrifos exposure averaging about 576-627 microg/day and indicated levels approximately 30% (range 0-250%) of the internal dose received by a typical subject exposed during a working day at the threshold limit value of 200 microg/m3. We modeled NCS results using linear mixed models with repeated measures. Although we found no consistent associations between interim chlorpyrifos exposure and NCS results, we identified several significant associations involving historic chlorpyrifos exposure. Most associations, however, reflected effects at low-exposure levels (< 20 mg/m3 x days) without further effects as exposure increased over a 10-fold range (20-220 mg/m3 x days). This suggested small differences among subjects with low or no chlorpyrifos exposure, rather than a dose-related deterioration among subjects with higher exposures. Two NCS results demonstrating apparent subclinical adverse dose effects showed significant but unexplained interaction with education level. The overall results provide little support for the hypothesis that chronic chlorpyrifos exposures at levels in the range associated with appreciable inhibition of B-esterases produce adverse dose effects on peripheral nerve electrophysiology suggestive of subclinical neuropathy.
我们对113名化学工人进行了神经传导研究（NCS），其中许多人职业性接触有机磷杀虫剂毒死蜱（O,O-二乙基-O-[3,5,6-三氯-2-吡啶基]-硫代磷酸酯），以确定亚临床神经病变的剂量效应。在这项双盲纵向研究中，我们估计了过去和中期的毒死蜱暴露量，并测量了毒死蜱代谢物3,5,6-三氯-2-吡啶醇（TCP）的排泄情况。暴露工人的TCP排泄情况表明，估计每日毒死蜱暴露量平均约为576 - 627微克/天，表明其水平约为在工作日接触阈值限值200微克/立方米的典型受试者所接受内部剂量的30%（范围为0 - 250%）。我们使用具有重复测量的线性混合模型对NCS结果进行建模。虽然我们没有发现中期毒死蜱暴露与NCS结果之间存在一致的关联，但我们确定了一些与过去毒死蜱暴露有关的显著关联。然而，大多数关联反映的是低暴露水平（<20毫克/立方米×天）的效应，随着暴露量在10倍范围内增加（20 - 220毫克/立方米×天）没有进一步的效应。这表明毒死蜱暴露量低或无暴露的受试者之间差异较小，而不是高暴露受试者中与剂量相关的病情恶化。两项显示明显亚临床不良剂量效应的NCS结果与教育水平存在显著但无法解释的相互作用。总体结果几乎不支持以下假设：与B - 酯酶明显抑制相关水平的慢性毒死蜱暴露会对周围神经电生理产生不良剂量效应，提示亚临床神经病变。
