Toxicology in vitro : an international journal published in association with BIBRA · 2009
Primary rat hepatocytes in chemical testing and QSAR predictive applicability.
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Tichý Milon, Pokorná Adéla, Hanzlíková Iveta, Nerudová Jana, Tumová Jana, Uzlová Rút
Аннотация
Primary rat hepatocytes were used to test acute toxicities of 16 neutral aliphatic alcohols, ketones and esters. Their effects on cell viability and metabolic function (ureogenesis, i.e. biotransformation of ornithine to urea) were measured and expressed as EC50 values. Log EC50 values from both tests correlated with the log partition coefficients for the chemicals between n-octanol and water and log P(ow)-based QSAR models were derived. Log EC50 (viability) tightly correlates with log EC50 (ureogenesis): log EC50 (viability)=0.91 log EC50 (ureogenesis)+0.06. Each of these toxic indices can be substituted by the other one. The toxic indices for both cell viability and metabolic disorder can be estimated using log EC50 for movement inhibition in the oligochaete Tubifex tubifex and the respective QSAR equation. It eliminates a usage of rats. Their correlations were proved and justified.