In vitro-Screening von Gefahrstoffen in der Arbeits- und Umweltmedizin

Chromium, especially the metal and its trivalent and hexavalent compounds, are of great industrial interest. As a matter of fact, chromium workers have an occupational risk. While trivalent chromium compounds are of low toxicity, the hexavalent compounds are strong oxidants which cause not only a direct tissue damage (=acute toxicity), but also possess a carcinogenic, mutagenic and teratogenic potential (=chronic toxicity). Since the kidney is the main target organ after oral and/or dermal uptake of hexavalent chromium is the kidney, tubular necrosis might be the result of an acute toxification. This report presents anin vitro assay with cultured renal epithelial cells which allows the evaluation of the acute toxicity not only of trivalent and hexavalent chromium compounds, but also of various hazardous substances used in industrial production process. As shown here, an acute toxic effect was not detectable for the trivalent chromium (chromium (III)-chloridehexahydrate) within 24 h of exposure to concentrations as high as 200 μmol/l. In contrast, renal epithelial cells which were exposed to hexavalent chromium (potassium chromate) for the same time period exhibited marked signs of toxicity such as a rounding and detachment of the cells from the floor of the culture plates, an elongation and perinuclear development of vacuoles in the vital cells which were still attached, as well as a cells swelling and cellular fragments caused as a result of necrotic cell death and subsequent lysis. This toxic effect was already observed at concentrations above 5 μmol/l. In conclusion, thein vitro assay might be a good tool for the screening of hazardous substances in industrial medicine. More-over, by using additional tests, the chronic toxicity of such substances can also be examined. The selection of specific cell strains such as hepatocytes, neural cells etc. also allows the evaluation of toxic effects in individual organs. Thein vitro assay can not only be applied for the investigation of basic mechanisms of toxification and detoxification of specific compounds, but also delivers a basis for the screening of the reactivity of individual hazardous substances. Finally, the assay would allow a reduction in animal experiments as well as the simultaneous testing of a reactivity to multiple, hazardous substances.