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。最近，各种人造矿物纤维（MMMF）已被使用，因为严重的健康疾病，包括间皮瘤报告暴露于石棉。采用细胞磁测量法、LDH释放试验、形态学观察和细胞毒性检测等方法，对纤维状二氧化钛（fTiO_2）、八钛酸钾晶须（PT）、微晶玻璃（MG）和岩棉（RW）4种MMMF的细胞毒性进行了评价。用磁法测定了被大鼠肺泡巨噬细胞吞噬的磁铁矿所辐射出的磁场迅速下降，这种现象被称为“弛豫”。这种松弛被认为是由于吞噬体在细胞骨架的驱动下随机旋转。以舒张延迟和LDH释放增加为基础的细胞毒作用表现为：fTiO_2和PT>MG>RW。实验组雄性大鼠经鼻吸入CdO（100纤维/m^3），每天3 h，连续5d，观察CdO对大鼠心肌细胞的舒张和LDH释放的影响，而InAs和复印机墨粉对大鼠心肌细胞的舒张和LDH释放的影响均为阴性。分别于染毒后即刻、染毒后1、2、4周处死大鼠，分析肺纤维计数和大小。暴露4周后，长度和宽度均显著降低。RW在肺中的持久性估计的半衰期短于以前报告的温石棉纤维的值。RW染毒组大鼠肺组织学变化最小，体外实验结果与体内实验结果一致。为了证实磁力测定法作为筛选试验的有效性，有必要进一步研究，以检查使用体外研究阳性的化学物质进行的体内研究。

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