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

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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.