RESUMEN
Typical in silico models for ecotoxicology focus on a few endpoints, but there is a need to increase the diversity of these models. This study proposes models using the NOEC for the harlequin fly (Chironomus riparius) and EC50 for swollen duckweed (Lemna gibba) for the first time. The data were derived from the EFSA OpenFoodTox database. The models were based on the correlation weights of molecular features used to calculate the 2D descriptor in CORAL software. The Monte Carlo method was used to calculate the correlation weights of the algorithms. The determination coefficients of the best models for the external validation set were 0.74 (NOAEC) and 0.85 (EC50).
RESUMEN
BACKGROUND: Poisoning from pesticides can be extremely hazardous for non-invasive species, such as bees, and humans causing nearly 300,000 deaths worldwide every year. Several pesticides are recognized as endocrine disruptors compounds that alter the production of the normal hormones mainly by acting through their interaction with nuclear receptors (NRs). Among the insecticides, one of the most used is pyriproxyfen. As analogous to the juvenile hormone, the pyriproxyfen acts in the bee's larval growth and creates malformations at the adult organism level. METHODS: This work aims to investigate the possible negative effects of pyriproxyfen and its metabolite, the 4'-OH-pyriproxyfen, on human and bee health. We particularly investigated the mechanism of binding of pyriproxyfen and its metabolite with ultraspiracle protein/ecdysone receptor (USP-EcR) dimer of A. mellifera and the relative heterodimer farnesoid X receptor/retinoid X receptor alpha (FXR-RXRα) of H. sapiens using molecular dynamic simulations. RESULTS: The results revealed that pyriproxyfen and its metabolite, the 4'-OH- pyriproxyfen, stabilize each dimer and resulted in stronger binders than the natural ligands. CONCLUSION: We demonstrated the endocrine interference of two pesticides and explained their possible mechanism of action. Furthermore, in vitro studies should be carried out to evaluate the biological effects of pyriproxyfen and its metabolite.