Spencer P S, Schaumburg H H
Environ Health Perspect. 1975 Jun;11:129-33. doi: 10.1289/ehp.7511129.
Acrylamide, widely employed as a vinyl monomer in the polymer industry, is a potent neurotoxin to man and to animals. The cumulative effect of prolonged, low-level exposure to acrylamide monomer is the insidious development of a progressive peripheral neuropathy. Sensory symptoms begin in the hands and feet (numbness, pins and needles), certain reflexes are lost and, with severe exposure, muscle weakness and atrophy occur in the extremities. The peripheral neuropathy may be supplemented by symptoms indicative of central nervous system damage (ataxia, tremor, somnolence and mental changes). The neuropathologic basis for this clinical picture has been determined in cats. Here, chronic acrylamide intoxication produces selective peripheral and central nerve fiber degeneration. Degeneration first occurs in the extremities of long and large nerve fibers which later undergo a progressive, seriate proximal axonal degeneration known as dying-back. Especially vulnerable are sensory axons supplying Pacinian corpuscles and muscle spindles in the hindfoot toepads, while adjacent motor nerve axons die back later. Distal central nerve fiber degeneration is seen in the medulla and the cerebellum. The neurotoxic property of acrylamide is of practical concern in two areas. One major problem is the protection of factory workers engaged in the manufacture of acrylamide. A sensitive test of neurologic function in these individuals, i.e., touch sensation, based on the experimental observation of the exquisite vulnerability of Pacinian corpuscles in acrylamide intoxicated cats, is presently under consideration. The second area for concern is the exposure of the populace to minute amounts of neurotoxic acrylamide monomer which contaminate acrylamide polymers currently deployed in the environment. Federal restrictions on the maximum permitted exposure to acrylamide, based on a largely clinical study of acrylamide neurotoxicity conducted ten years ago, may require a re-evaluation in the light of recent advances which have pinpointed the initial sites of nerve fiber degeneration.
丙烯酰胺在聚合物工业中广泛用作乙烯基单体,是一种对人和动物都有强烈毒性的神经毒素。长期低剂量接触丙烯酰胺单体的累积效应是逐渐发展出一种隐匿性的进行性周围神经病变。感觉症状始于手部和足部(麻木、刺痛感),某些反射消失,严重接触时,四肢会出现肌肉无力和萎缩。周围神经病变可能伴有中枢神经系统损伤的症状(共济失调、震颤、嗜睡和精神变化)。这种临床症状的神经病理学基础已在猫身上得到确定。在此,慢性丙烯酰胺中毒会导致选择性的周围和中枢神经纤维变性。变性首先发生在长而大的神经纤维末端,随后这些神经纤维会经历一种渐进性的、连续的近端轴突变性,即所谓的“逆行性变性”。特别容易受损的是供应后足趾垫中帕西尼小体和肌梭的感觉轴突,而相邻的运动神经轴突稍后才会发生逆行性变性。在延髓和小脑中可见中枢神经纤维的远端变性。丙烯酰胺的神经毒性在两个方面具有实际意义。一个主要问题是保护从事丙烯酰胺生产的工厂工人。基于对丙烯酰胺中毒猫中帕西尼小体极易受损这一实验观察,目前正在考虑对这些个体进行一项敏感的神经功能测试,即触觉测试。另一个值得关注的领域是民众接触到微量神经毒性丙烯酰胺单体,这些单体污染了目前环境中使用的丙烯酰胺聚合物。基于十年前对丙烯酰胺神经毒性进行的一项主要临床研究,联邦政府对丙烯酰胺的最大允许接触量的限制,可能需要根据最近确定神经纤维变性起始部位的进展进行重新评估。