STUDY OF SAFETY ASSESSMENT OF NEW MINERAL FIBERS USING MAKERS IN LUNG FIBROSIS-RELATED BIOLOGICAL DIAGNOSIS

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We studied about usefulness of new method which measured lung fibrosis-related cytokines released from alveolar macropahges in safety evaluation of mineral fibers including asbestos substitute.(1) TNF-alpha, IL-beta, IL-8, MIP-1alpha and GRO released from human alveolar macrophages were increased by UICC amosite, crocidolite and chrysotile.(2) Co-culture of human fibrobrasts accelerated the increases of IL-1beta and GRO in human alvelar macrophages with asbestos.(3) On the basis of finding in human alveolar macrophage, we tested effects of three kind of ceramic fibers and micro glass wool including MMMF,three kind of whiskers, UICC crocidolite and tremolite on IL-1beta and TNF-alpha released from mouse macrophage-like cells.(4) In cytotoxicity test, all of these fibers in 1-10mug/ml showed no-effect and Sic whisker of 100mug-1mg/ml only revealed high cytotoxicity.(5) K-Ti-O- and TiO whiskers showed same effect, ceramic fiber group, micro glass wool and SiC whisker showed high sensitivity in MTT test when compared with UICC crocidolite.(6) Although TNF-alpha in cell culture medium increased by MMMF or whisker compared with UICC crocidolite, effect of ceramic fiber was bigger than that of whiskers.(7) Intracellular content of IL-1beta showed same level or a little increase in MMMF,and whisker revealed lower than that of UICC crocidolite.From these results, it suggested that measurements of TNF-alpha and IL-beta including lung fibrosis-related cytokines might be useful in safety evaluation of asbestos substitute. However, different finding between cytotoxicity test, MTT test, TNF-alpha and IL-beta required the comparison with in vivo and in vitro experiments in these asbestos substitutes.