Do co-formulants influence plant protection product genotoxicity?

Plant protection products (PPPs) contain active substances (AS) providing pesticidal activity and co-formulants supporting efficacy. AS undergo extensive safety assessment, including genotoxicity testing, while PPPs are assessed only for acute and local toxicity. Genotoxicity may contribute to long-term effects like carcinogenesis, and as operators are exposed to concentrated PPPs and spray dilutions, co-formulant toxicity and interactions require attention. An in silico analysis was conducted to identify potentially genotoxic co-formulants and prioritise PPPs for in vitro testing. Four prioritised co-formulants exceeded 1 % concentration in eight PPPs, but existing data ruled out further investigation. AS with known in vitro genotoxic potential were assessed for toxicokinetic interaction with co-formulants. The genotoxic potential of PPPs containing metiram, a dithiocarbamate fungicide, and pendimethalin, a dinitroaniline herbicide, was assessed in V79 cells using in vitro micronucleus test. No difference was observed between metiram and its PPP, whereas a 2-fold increase in micronuclei formation occurred in formulated PPP compared to pendimethalin alone at highest tested concentration. These findings indicate that co-formulants, although unlikely to be genotoxic on their own, may influence the genotoxic potential of pendimethalin in the tested PPP. Therefore, AS showing genotoxic potential in vitro should be considered for testing in respective formulated PPPs.