Critical evaluation of 2-ethylhexyl acrylate dermal carcinogenicity studies using contemporary criteria.

Skin tumors have been observed in C3H/HeJ mice following treatment with high and strongly irritating concentrations of 2-ethylhexyl acrylate (2-EHA). Dermal carcinogenicity studies performed with 2-EHA are reviewed, contrasting the results in two mouse strains (C3H/HeJ and NMRI) under different dosing regimens. Application of contemporary evaluation criteria to the existing dermal carcinogenicity dataset demonstrates that 2-EHA induces skin tumors only at concentrations exceeding an maximum tolerated dose (MTD) and in the immune-dysregulated C3H/HeJ mouse model. Overall, the available chronic toxicity and genotoxicity data on 2-EHA support a non-genotoxic chemical irritant mechanism, whereby chronic irritation leads to inflammation, tissue injury, and wound repair, the latter of which is disrupted in C3H/HeJ mice and leads to tumor formation. Tumor response information in excess of an MTD should not be considered in a human hazard or risk assessment paradigm. For the purposes of an appropriate hazard assessment, 2-EHA did not cause or initiate dermal carcinogenesis in an immune competent (NMRI) mouse model, and, even in the immune compromised C3H/HeJ model, did not induce skin tumors at doses which did not exceed the MTD.

A strategy to reduce the use of fish in acute ecotoxicity testing of new chemical substances notified in the European Union.

This study explores the applicability of a fish acute threshold (step-down) test approach for the assessment of new chemical substances notified in the EU. The proposed approach basically implies replacing the fish LC50 toxicity test with a simple acute threshold test and thus reducing the number of fish used and also costs. The fish test would be performed only at one concentration, the lowest between the EC50 concentrations obtained with previous testing with algae and daphnia. When fish would be more sensitive than algae and daphnia, testing with fish would be continued at lower concentrations (step-down). From step-down test results the LC50 value can be obtained by applying the binominal method of interpolation. These data can be used together with algal and daphnid data to provide the same Predicted No Effect Concentration values. The acute aquatic toxicity data used in this evaluation were extracted from the New Chemicals Database of the European Chemicals Bureau. The results show that 53.6-71.2% reduction of the number of fish used would be possible when applying this new testing strategy and suggest its use for regulatory purposes.