human toxicity prediction

/Tag:human toxicity prediction

Evaluation of the Cytotoxic Effects of MEIC Chemicals 31–50 on Primary Culture of Rat Hepatocytes and Hepatic and Non-hepatic Cell Lines

Xavier Ponsoda, Cristina Núñez, José Vicente Castell and Maria
José Gómez-Lechón

The cytotoxicities of 20 chemicals (numbers 31–50) from the Multicenter Evaluation of In Vitro Cytotoxicity (MEIC) programme were assessed with a primary culture of rat hepatocytes and with two hepatic cell lines (Hep G2 and FaO) and one non-hepatic cell line (3T3). The cytotoxicities of the chemicals were evaluated by using the MTT test after the cells had been exposed to the chemicals for 24 hours. For a better evaluation of results, dose–response curves were mathematically linearised and cytotoxicity was expressed as IC50 values and IC10 values (the concentration causing 50% and 10% loss of cell viability, respectively). We found that all the compounds showed similar acute basal cytotoxicity in all four cellular systems (regardless of whether the cells were, or were not, metabolically competent or were or were not of human origin). When these results were used to predicit human toxicity in terms of a mathematical parameter (prediction error [PE]), we found that all four systems gave similar predictions of human toxicity. The best cytotoxicity parameter included in the PE calculation was the IC50/10, because of an underestimation of human toxicity by in vitro systems. However, when PEs were calculated for rodent toxicity, better results were obtained. Data from the literature obtained by using other experimental models for predicting human toxicity were analysed according to the same criteria. We conclude that cellular systems are better predictive tools for human toxicity than are prokaryotic cells or whole-organism models.
You need to register (for free) to download this article. Please log in/register here.