Comparative cytotoxicity of plant protection products and their active ingredients

Toxicological testing of plant protection products (PPPs) is a legal requirement in the EU. The whole PPP formulation is tested for acute endpoints in vivo during approval procedure of PPPs. However, alternative methods such as the CLP calculation method (CM) are employed increasingly. In the first part of this study we analysed PPPs for the correlation of GHS classifications resulting mainly from in vivo LD₅₀-values with classifications obtained from calculated LD₅₀-values using the CM. Accordingly, the CM predicted 80% of the PPPs correctly. However 31% of classified products were not identified revealing a considerable inaccuracy of this method. Based on these results ten PPPs and corresponding ASs were further tested in a cytotoxicity assay employing 3T3 and hFF cells (one PPP and corresponding AS were tested in HepaRG cells). The study outcome revealed that the cytotoxicity data did not reliably reflect differences in toxicity between ASs and PPPs. Especially organic solvent based formulations demonstrated a higher cytotoxicity than water based formulations independently to their toxicity in vivo. Overall, the cytotoxicity test did not provide a more robust method than the CM. However, the database consisting of ten PPPs was small and therefore no robust conclusions can be drawn.