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Mechanistic studies on reproductive toxicity and neurotoxicity of alternatives to chlorofluorocarbons and their risk assessment

氯氟烃替代品生殖毒性和神经毒性的机理研究及风险评估

基本信息

批准号：
10470106
负责人：
TAKEUCHI Yasuhiro
金额：
$ 9.66万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

(1) Study on female reproductive toxicity of 2-bromopropane.Experiments using Wistar female rats revealed that disruption of ovary function was due to the destruction through apoptosis of primordial follicle and its oocyte.(2) Study on male reproductive toxicity of 2-bromopropane.The experiments using Wistar male rats revealed the primary adverse effect on spermatogonia and secondary apoptosis of spermatocyte. Decrease in Bcl-2 and increase in Bax were thought to induce primary apoptosis of spermatogonia, and the increase in Fas might induce secondary apoptosis of spermatocyte.(3) Study on neurotoxicity and reproductive toxicity of 1-bromopropane.A twelve-weeks study using Wistar male rats revealed that 1-bromopropane is dose-dependently neurotoxic and disrupts spermiation at the final step of spermatogenesis. In addition, 1-bromopropane modified SH-base in brain and decreased creatine kinase activity.(4) Study on dose-effect relationship in bromopropane factory workers.The investigation of 2-bromopropane factory did not show so severe disruption of reproductive and hematopoietic function as seen in the Korean cases. However, the possibility of adverse effects on hematopoiesis could not be disproved. The investigation of the 1-bromopropane factory showed that 1-bromopropane might impair peripheral nerves in humans at several dozen ppm.

(1)2-溴丙烷对雌性大鼠生殖毒性的研究：Wistar雌性大鼠的实验表明，2-溴丙烷对卵巢功能的破坏是由于原始卵泡及其卵母细胞的凋亡所致。(2)2-溴丙烷对雄性大鼠生殖系统的毒性研究表明，2-溴丙烷对大鼠精原细胞的毒性作用主要表现为初级毒性作用，次级毒性作用表现为精原细胞凋亡。Bcl-2的表达减少和Bax的表达增加可诱导精原细胞的初级凋亡，Fas的表达增加可诱导精母细胞的次级凋亡。(3)1-溴丙烷的神经毒性和生殖毒性研究：对Wistar雄性大鼠进行的一项为期12周的研究表明，1-溴丙烷具有剂量依赖性神经毒性，并在精子发生的最后一步破坏精子形成。此外，1-溴丙烷修饰脑内SH-碱，降低肌酸激酶活性。(4)溴丙烷工厂工人的剂量-效应关系的研究2-溴丙烷工厂的调查未显示象韩国病例那样严重的生殖和造血功能破坏。然而，不能否认对造血产生不良影响的可能性。对1-溴丙烷工厂的调查表明，1-溴丙烷在几十ppm时可能损害人类的外周神经。