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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470106/
• 关键词: 2-bromopropane; 1-bromopropane; reproductive toxicity; neurotoxicity; apoptosis; SH base; creatine kinase; dose-effect relationship; フロン代替物質; 神経伝導速度; 遠位潜時; 吸入曝露; ラット; 精子; 性周期; GSH; ノ-ブロモプロパン; 神経病理組織; 精子異常; 雌性周期

(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-溴丙烷的雌性生殖毒性研究。Wistar雌性大鼠实验表明，卵巢功能的破坏是由于原始卵泡及其卵母细胞凋亡被破坏所致。(2) 2-溴丙烷的雄性生殖毒性研究.用Wistar雄性大鼠进行的实验揭示了对精原细胞的主要不良影响和精母细胞的二次凋亡。 Bcl-2的减少和Bax的增加被认为可诱导精原细胞的原发性凋亡，而Fas的增加可能会诱导精母细胞的继发性凋亡。(3)1-溴丙烷的神经毒性和生殖毒性研究。一项为期12周的研究Wistar 雄性大鼠发现 1-溴丙烷具有剂量依赖性神经毒性，并会在精子发生的最后一步扰乱精子形成。另外，1-溴丙烷修饰脑内的SH-碱基，降低肌酸激酶活性。(4)溴丙烷工厂工人的剂量效应关系研究。2-溴丙烷工厂的调查未发现对生殖和造血功能有如此严重的破坏。正如韩国案例中所见。然而，不能否认对造血功能产生不利影响的可能性。对1-溴丙烷工厂的调查表明，1-溴丙烷在几十ppm的情况下可能会损害人体的末梢神经。

项目成果

市原学: "産業化学物質の生殖毒性"Eco Industry. 4. 25-32 (1999)

Manabu Ichihara：“工业化学品的生殖毒性”Eco Industry 4. 25-32 (1999)。

Xie, Zhenlin: "Skin impairment by chemicals, contact dermatitis."Iyaku Journal. 36. 5-13 (2000)

谢振林：“化学物质损伤皮肤，接触性皮炎。”医药杂志。

Ichihara, Gaku: "Urinary 2,5-hexanedione increased with potentiation of neurotoxicity in chronic co-exposure to n-hexane and methyl ethyl ketone."International Archives of Occupational and Environmental Health. 71. 100-104 (1998)

Ichihara, Gaku：“长期同时接触正己烷和甲基乙基酮时，尿中 2,5-己二酮会随着神经毒性的增强而增加。”国际职业与环境健康档案。

Takeuchi, Yasuhiro: "Health impairment by organic solvents, problem of organic solvents intoxication to resolve."Sangyo Eiseigaku Zasshi. 40. 129-130 (1998)

Takeuchi, Yasuhiro：“有机溶剂损害健康，解决有机溶剂中毒问题。”Sangyo Eiseigaku Zasshi。

Ichihara, Gaku: "Neurotoxicity of 2-bromopropane and 1-bromopropane, substitutes for chlorofluorocarbons."Peripheral Nerve. 9. 69-76 (1998)

Ichihara, Gaku：“2-溴丙烷和 1-溴丙烷的神经毒性，氯氟烃的替代品。”周围神经。