Human acute toxicity prediction of the first 50 MEIC chemicals by a battery of ecotoxicological tests and physicochemical properties

Abstract

Five acute bioassays consisting of three cyst-based tests (with Artemia salina, Streptocephalus proboscideus and Brachionus calyciflorus), the Daphnia magna test and the bacterial luminescence inhibition test ( Photobacterium phosphoreum) are used to determine the acute toxicity of the 50 priority chemicals of the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) programme. These tests and five physicochemical properties ( n-octanol-water partition coefficient, molecular weight, melting point, boiling point and density) are evaluated either singly or in combination to predict human acute toxicity. Acute toxicity in humans is expressed both as oral lethal doses (HLD) and as lethal concentrations (HLC) derived from clinical cases. A comparison has also been made between the individual tests and the conventional rodent tests, as well as between rodent tests and the batteries resulting from partial least squares (PLS), with regard to their predictive power for acute toxicity in humans. Results from univariate regression show that the predictive potential of bioassays (both ecotoxicological and rodent tests) is generally superior to that of individual physicochemical properties for HLD. For HLC prediction, however, no consistent trend could be discerned that indicated whether bioassays are better estimators than physicochemical parameters. Generally, the batteries resulting from PLS regression seem to be more predictive than rodent tests or any of the individual tests. Prediction of HLD appears to be dependent on the phylogeny of the test species: cructaceans, for example, appear to be more important components in the test battery than rotifers and bacteria. For HLC prediction, one anostracan and one cladoceran crustacean are considered to be important. When considering both ecotoxicological tests and physicochemical properties, the battery based on the molecular weight and the cladoceran crustacean predicts HLC substantially better than any other combination.