Analysis of the correlation between in vitro cytotoxicity data and acute toxic effects in humans

S Casati¹, S Hoffmann¹, JA Strickland², MW Paris², WS Stokes³, RR Tice², I Malerba¹

1. European Commission, JRC, IHCP, ECVAM, Ispra, Italy
2. NICEATM, RTP, USA / ILS, Inc, RTP, USA
3. NICEATM, RTP, USA

Several studies have shown that in vitro cell systems can predict acute toxic effects in vivo. NICEATM and ECVAM recently conducted a multi-laboratory validation study to assess the predictive capacity of two in vitro basal cytotoxicity assays primarily for predicting rodent, but also human acute toxicity. Seventy-two coded chemicals were tested in mouse 3T3 fibroblasts and normal human epidermal keratinocytes (NHK) using the neutral red uptake (NRU) assay. Forty-one chemicals used in the study are MEMO chemicals, i.e. chemicals for which relevant human toxicity data exists. The collection of human toxicity data for four other chemicals, for which these data were lacking, was commissioned by ECVAM. A preliminary analysis conducted with twelve chemicals showed a good correlation for both cell types (3T3 cells: R2 = 0.787, NHK: R2 = 0.886) between in vitro IC50 values (i.e. the concentration of a chemical that inhibits cell growth by 50%) and peak serum concentration in humans derived from time-related lethal and sub-lethal concentrations curves. However, the in vitro IC50 values for cadmium chloride and ethylene glycol under- and over-predicted human toxicity by more than 10-fold respectively. The evaluation of the correlation between human data and the IC50 values for the complete set of chemicals is ongoing. ILS staff supported by NIEHS contract N01-ES 35504.

Date: Tuesday, August 23, 2005, 10.00-12.00 h, Estrel Hall C5/C6

5.6 Session: In Vitro Aproaches for Determining Acute Systemic Toxicity.