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[1,1,1-三氯乙烷(甲基氯仿)在工业生产中的使用:神经毒性风险]

[The use of 1,1,1-trichloroethane (methylchloroform) in industrial operations: the neurotoxicity risk].

作者信息

Fernicola C, Govoni S, Coniglio L, Daniele E, Trabucchi M

机构信息

Unità Operativa Tutela della Salute nei Luoghi di Lavoro, USL 41, Brescia.

出版信息

Med Lav. 1991 Jan-Feb;82(1):38-49.

PMID:1865846
Abstract

1,1,1-Trichloroethane (1,1,1-TE) is a widely used organic solvent which is thought to be relatively safe. The present review is mainly focused on the neurotoxic effects of 1,1,1-TE. Concentrations above 350 ppm are considered capable of negatively conditioning the performance of the exposed person, in particular reaction time and manual abilities. Peripheral neuropathies have also been described. More recently the potential neurotoxicity of 1,1,1-TE has been underscored by animal studies investigating the effects of this substance in neurobehavioral tests and on neurochemical parameters. 1,1,1-TE alters the motor activity in small laboratory rodents. In fixed interval responding in mice, the effects of 1,1,1-TE are qualitatively similar to those of other volatile (ethanol) and non volatile (benzodiazepines and barbiturates) CNS depressants. In addition, in drug discrimination procedures 1,1,1-TE shares discriminative stimulus properties with barbiturates, toluene, halotane, and oxazepam indicating that this solvent has behavioral effects in common with central nervous system depressant drugs. From a neurochemical point of view long-term exposure to 1,1,1-TE induces astrogliosis in the cerebral cortex of gerbils as indicated by an increased concentration of glial fibrillary acidic protein. In addition low dose inhalation of 1,1,1-TE for 3 months decreases DNA concentrations in several brain regions of the gerbil. 1,1,1-TE affects also brain concentrations of cAMP and cGMP as well as calcium ion control, possibly through an action on voltage-dependent calcium channels. It has been also suggested that intermediate metabolites of 1,1,1-TE may give origin to condensation products with dopamine, ultimately impairing dopaminergic transmission. Some of the neurochemical effects of 1,1,1-TE are shared by other chlorinated organic solvents as well as by CNS depressants. The literature analyzed indicates that 1,1,1-TE may exert significant neurotoxic effects suggesting that more caution in its use is needed and that attention should be paid to the possibility of an additive effect of 1,1,1-TE and CNS depressants (ethanol, barbiturates, benzodiazepines and other volatile solvents) giving origin to severe neurotoxicity.

摘要

1,1,1-三氯乙烷(1,1,1-TE)是一种广泛使用的有机溶剂,人们认为它相对安全。本综述主要关注1,1,1-TE的神经毒性作用。浓度高于350 ppm被认为会对接触者的表现产生负面影响,尤其是反应时间和手部操作能力。外周神经病变也有相关描述。最近,动物研究通过调查该物质在神经行为测试和神经化学参数方面的影响,强调了1,1,1-TE潜在的神经毒性。1,1,1-TE会改变小型实验啮齿动物的运动活动。在小鼠的固定间隔反应中,1,1,1-TE的作用在性质上与其他挥发性(乙醇)和非挥发性(苯二氮䓬类和巴比妥类)中枢神经系统抑制剂相似。此外,在药物辨别程序中,1,1,1-TE与巴比妥类、甲苯、氟烷和奥沙西泮具有共同的辨别刺激特性,这表明这种溶剂与中枢神经系统抑制药物具有共同的行为效应。从神经化学角度来看,长期接触1,1,1-TE会导致沙鼠大脑皮层星形胶质细胞增生,这表现为胶质纤维酸性蛋白浓度增加。此外,低剂量吸入1,1,1-TE 3个月会降低沙鼠几个脑区的DNA浓度。1,1,1-TE还会影响大脑中cAMP和cGMP的浓度以及钙离子调控,可能是通过作用于电压依赖性钙通道。也有人提出,1,1,1-TE的中间代谢产物可能与多巴胺产生缩合产物,最终损害多巴胺能传递。1,1,1-TE的一些神经化学作用也为其他氯化有机溶剂以及中枢神经系统抑制剂所共有。分析的文献表明,1,1,1-TE可能会产生显著的神经毒性作用,这表明在使用时需要更加谨慎,并且应该关注1,1,1-TE与中枢神经系统抑制剂(乙醇、巴比妥类、苯二氮䓬类和其他挥发性溶剂)产生相加效应导致严重神经毒性的可能性。

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