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Alternatives to Laboratory Animals - ATLA

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Structural Basis of the Toxicity of Chemicals in Cultured Human HeLa Cells

Xinyu Zhu and Herbert S. Rosenkranz

A coherent structure-activity relationship (SAR) model was derived from data based on the toxicity of chemicals in cultured human HeLa cells. The ability to construct such a model indicates that toxicity is a function of a finite number of mechanisms. A comparison of the HeLa SAR model with models that describe other toxicological phenomena demonstrated significant mechanistic similarities with systemic toxicity in rodents and ocular irritation in rabbits. Overall, the present analyses support the hypothesis that the inclusion of a battery of cell toxicity assays together with toxicokinetic models will result in a more predictive model of systemic toxicity in humans.