Safety assessment of chemical substances by in vitro and in vivo magnetometry

通过体外和体内磁力测定法评估化学物质的安全性

• 批准号: 14370127
• 负责人: AIZAWA Yoshiharu
• 金额: $ 8.64万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14370127/
• 关键词: magnetometry; man-made-mineral fibers; rock wool; cyototoxicity; inhalation; biopersistence; nose-only inhalation; safety of chemical substance; クリソタイル; 肺胞マクロファージ; 細胞傷害性; 細胞磁界測定; 肺内繊維数; 肺磁界測定; 乳酸脱水素酵素; アポトーシス; Micro glass fiber

Several thousands of chemical substances are newly produced in Japan. A system of safety assessment for these new substances is required. Recently, various kinds of man-made-mineral fibers (MMMFs) have been used, since serious health disorders including mesotheliomas were reported by an exposure to asbestos. We evaluated the cytotoxicity of 4 types of MMMFs, fibrous titanium dioxide (fTiO_2), potassium octatitanate whisker (PT), microglass (MG) and rock wool (RW) by cytomagnetometry, as well as LDH release assays, morphological observations and apoptotis detections. Also evaluated were other substances such as indium arsenide (InAs), CdO and photocopier toner.By magnetometry, the remanent fields radiated from magnetites engulfed by alveolar macrophages of rats decreased rapidly and this phenomenon is named ‘relaxation'. The relaxation is thought attributed to the random rotation of phagosomes driven by cytoskeleton. Cytotoxicity on the basis of delayed relaxation and increased LDH release was observed as follows, fTiO_2 and PT>MG>RW. The exposure to CdO caused marked effects on the relaxation and LDH release, while the effects of both InAs and photocopier toner were negative.Male rats were exposed to target exposure concentration of RW 100 fibers/m^3 by nasal inhalation 3 hours daily for 5 consecutive days. Rats were sacrificed shortly after exposure, 1,2 and 4 weeks after exposure and the fiber counts and sizes in the lungs were analyzed. Both the length and width significantly decreased 4 weeks after exposure. The persistence of RW in the lungs estimated by a half-life was shorter than previously reported value of chrysotile fibers. The histological changes of the lungs in RW-exposed rats were minimum.The in vitro results of RW exposure coincided with the in vivo results. To confirm the usefulness of magnetometry as a screening test, further study is necessary to examine the in vivo study using chemical substance with positive in vitro study.

日本新生产了数千种化学物质。需要对这些新物质进行安全评估系统。最近，由于接触石棉而导致包括间皮瘤在内的严重健康疾病的报道，各种人造矿物纤维（MMMF）已被使用。我们通过细胞磁力测定、LDH 释放测定、形态学观察和凋亡检测评估了 4 种 MMMF、纤维状二氧化钛 (fTiO_2)、八钛酸钾晶须 (PT)、微玻璃 (MG) 和岩棉 (RW) 的细胞毒性。还评估了其他物质，如砷化铟（InAs）、CdO和复印机墨粉。通过磁力测量，大鼠肺泡巨噬细胞吞噬的磁​​铁矿辐射的剩余磁场迅速下降，这种现象被称为“松弛”。这种松弛被认为归因于细胞骨架驱动的吞噬体的随机旋转。观察到基于延迟舒张和增加LDH释放的细胞毒性如下：fTiO_2和PT>MG>RW。 CdO暴露对松弛和LDH释放有显着影响，而InAs和复印机碳粉的影响均为阴性。雄性大鼠通过鼻吸入每天3小时暴露于目标暴露浓度RW 100纤维/m^3，连续5天。暴露后不久、暴露后 1,2 和 4 周处死大鼠，并分析肺中的纤维数量和大小。暴露后4周，长度和宽度均显着减小。通过半衰期估计的 RW 在肺部的持久性比之前报道的温石棉纤维的值短。 RW染毒大鼠肺部组织学变化最小。RW染毒的体外结果与体内结果一致。为了确认磁力测量作为筛选测试的有用性，需要进一步研究使用体外研究呈阳性的化学物质来检验体内研究。

项目成果

Comparative cytotoxicity study of rock wool and chrysotile by cell nmagnetometric evaluation

细胞磁力评价法比较岩棉和温石棉的细胞毒性研究

• 发表时间: 2003
• 期刊: Inhalation Toxicorogy 15
• 作者: Yuichiro Kudo;Hisako shinji;Yuichiro Kudo;Hisako Shinji;Hisako Shinji;Hisako Shinji;Yuichiro Kudo
• 通讯作者: Yuichiro Kudo

Mitsuyasu Watanabe: "Magnetometric Evaluation for Cytotoxicity of Potassium Octatitanate Whisker on Alveolar Macrophages of Fischer 344 Rats"J Occup Health. 44. 321-328 (2002)

Mitsuyasu Watanabe：“八钛酸钾晶须对 Fischer 344 大鼠肺泡巨噬细胞细胞毒性的磁力评估”J Occup Health。

Magnetometric evaluation for the cytotoxicity of potassium octatitanate whisker on alveolar macrophages of Fischer 344 rats.

磁力法评估八钛酸钾晶须对 Fischer 344 大鼠肺泡巨噬细胞的细胞毒性。

• 发表时间: 2002
• 期刊: J.Occup.Health 44
• 作者: Yuichiro Kudo;Hisako shinji;Yuichiro Kudo;Hisako Shinji;Hisako Shinji;Hisako Shinji;Yuichiro Kudo;Masato Niitsukya;Yuichiro Kudo;Masato Niitsuya;Yuichiro Kudo;Masato Niitsuya;Mitsuyasu Watanabe;Mitsuyasu Watanabe;Mitsuyasu Watanabe;Watanabe Mitsuyasu
• 通讯作者: Watanabe Mitsuyasu

In vitro toxicity of indium arsenide to alveolar macrophages evaluated by magnetometry, cytochemistry and morphological analysis

通过磁力测定、细胞化学和形态分析评估砷化铟对肺泡巨噬细胞的体外毒性

• 发表时间: 2002
• 期刊: Toxicology Letters 134
• 作者: Yuichiro Kudo;Hisako shinji;Yuichiro Kudo;Hisako Shinji;Hisako Shinji;Hisako Shinji;Yuichiro Kudo;Masato Niitsukya;Yuichiro Kudo;Masato Niitsuya;Yuichiro Kudo;Masato Niitsuya;Mitsuyasu Watanabe;Mitsuyasu Watanabe;Mitsuyasu Watanabe;Watanabe Mitsuyasu;Mitsuyasu Watanabe;松村康弘ら;Mitsushi Okada
• 通讯作者: Mitsushi Okada

Magnetometric Evaluation for Cytotoxicity of Potassium Octatitanate Whisker on Alveolar Macrophages of Fischer 344 Rats

八钛酸钾晶须对 Fischer 344 大鼠肺泡巨噬细胞细胞毒性的磁力评价

• 发表时间: 2002
• 期刊: J Occup Health 44
• 作者: Yuichiro Kudo;Hisako shinji;Yuichiro Kudo;Hisako Shinji;Hisako Shinji;Hisako Shinji;Yuichiro Kudo;Masato Niitsukya;Yuichiro Kudo;Masato Niitsuya;Yuichiro Kudo;Masato Niitsuya;Mitsuyasu Watanabe;Mitsuyasu Watanabe
• 通讯作者: Mitsuyasu Watanabe