Landrigan P J, Graham D G, Thomas R D
Department of Community Medicine, Mount Sinai School of Medicine, New York 10029.
Environ Res. 1993 Apr;61(1):157-63. doi: 10.1006/enrs.1993.1060.
Toxic chemicals in the environment can cause a wide range of neurological disease. High-dose exposures to environmental neurotoxicants have produced encephalopathy in children ingesting chips of lead-based paint, blindness in persons who ingested methanol, blindness and ataxia in persons who consumed organic mercury, spinal cord degeneration and peripheral neuropathy in persons exposed to tri-ortho-cresyl phosphate (TOCP), and Parkinsonism in persons exposed to MPTP or to manganese. Environmental neurotoxicants have also been shown to produce a wide range of subclinical neurotoxic effects, including reduction in intelligence, impairment in reasoning ability, shortening of attention span, and alternation of behavior. The first step in the prevention of environmental neurotoxicity is to test chemicals for their toxic potential. More than 70,000 chemicals are currently in commerce. However, except for pharmaceuticals, fewer than 10% of these chemicals have been tested for neurotoxicity. A logical approach to neurotoxicologic assessment of chemical substances will build on and extend currently available test systems. It will have a tiered structure. The first or screening tier will consist of tests to measure obvious structural and functional changes, often a functional observational battery. Subsequent levels of testing will be guided by the results of initial screening. Toxicologic testing must be supplemented by epidemiologic surveillance of populations exposed to known and suspect neurotoxicants. Screening programs in these populations designed to detect excessive absorption of a neurotoxic agent or subclinical neurological dysfunction can be useful in identifying affected individuals before severe disability occurs.
环境中的有毒化学物质可引发多种神经疾病。高剂量接触环境神经毒物会导致摄入含铅油漆碎屑的儿童患脑病,摄入甲醇的人失明,食用有机汞的人失明和共济失调,接触磷酸三邻甲苯酯(TOCP)的人脊髓退化和周围神经病变,以及接触MPTP或锰的人患帕金森症。环境神经毒物还被证明会产生一系列亚临床神经毒性作用,包括智力下降、推理能力受损、注意力持续时间缩短和行为改变。预防环境神经毒性的第一步是测试化学物质的潜在毒性。目前有超过7万种化学物质在商业流通。然而,除了药品外,这些化学物质中接受神经毒性测试的不到10%。对化学物质进行神经毒理学评估的合理方法将基于并扩展现有的测试系统。它将具有分层结构。第一层或筛选层将包括测量明显结构和功能变化的测试,通常是一个功能观察组合。后续的测试水平将由初始筛选的结果指导。毒理学测试必须辅以对接触已知和可疑神经毒物人群的流行病学监测。在这些人群中设计的旨在检测神经毒物过度吸收或亚临床神经功能障碍的筛查项目,在严重残疾发生之前识别受影响个体方面可能会很有用。