Comparative Acute Cytotoxicities of 37 Xenobiotics Detected in Drinking Water to Rat Hepatocyte Primary Culture

概要

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To evaluate the toxicities of 37 xenobiotics detected in drinking water ; primary cultures of rat hepatocytes were treated with the xenobiotics at a concentration of 0.5 mM. The toxicities were assessed by four cellular markers : leakage of intracellular lactate dehydrogenase (LDH) activity, glycogenolytic activity as a specific function of hepatocytes, intracellular glutathione content, and observations of cytopathic effects. The cytotoxic assay revealed that pesticides of xenobiotics used in the current study were the most toxic at μM levels, that phenolic compounds had potent toxicity for the cultured cells while benzoic compounds did not, and that 3-carbon compounds with substitution of hydrogen to bromine or chlorine at both positions 1 and 3 were highly toxic. The order of hepatotoxicity on the basis of IC_<50> was, 1,3-dichloro-2-propanone > pentachlorophenol ⩾ 1,2-dibromo-3-chloro-propane > heptachlor > 2,4,6-trichlorophenol ⩾ 2,4,6-tribromophenol. Since lag times were observed for the expression of cytotoxicity by the pesticides, biotransformation appeared important for the toxicity. Currently the concentration of pesticides is very low in the environment, and therefore the possibility of causing an impact on human health is low. However, the long lifetime and high lipophilicity of pesticides give them the potential to become some of the greatest environmental toxicants.
社団法人日本薬学会の論文
1990-08-31