The intensive use of pesticides has led to their increasing presence in water, soil, and agricultural products. Mounting evidence indicates that some pesticides may be endocrine disrupting chemicals (EDCs), being therefore harmful for the human health and the environment. In this study, three pesticides, glyphosate, thiacloprid, and imidacloprid, were tested for their ability to interfere with estrogen biosynthesis and/or signaling, to evaluate their potential action as EDCs. Among the tested compounds, only glyphosate inhibited aromatase activity (up to 30%) via a non-competitive inhibition or a mixed inhibition mechanism depending on the concentration applied. Then, the ability of the three pesticides to induce an estrogenic activity was tested in MELN cells. When compared to 17β-estradiol, thiacloprid and imidacloprid induced an estrogenic activity at the highest concentrations tested with a relative potency of 5.4 × 10⁻¹⁰ and 3.7 × 10⁻⁹, respectively. Molecular dynamics and docking simulations predicted the potential binding sites and the binding mode of the three pesticides on the structure of the two key targets, providing a rational for their mechanism as EDCs. The results demonstrate that the three pesticides are potential EDCs as glyphosate acts as an aromatase inhibitor, whereas imidacloprid and thiacloprid can interfere with estrogen induced signaling.

Pesticides are widely applied all over the world, and pesticide exposure can induce different biological effects posing a possible threat to human health. Due to their effects on the endocrine system, some pesticides are classified as endocrine disruptors. The aim of the study is to assess the interference of five pesticides on estrogen biosynthesis and estrogen signaling. Three neonicotinoid insecticides (Acetamiprid, Clothianidin, and Thiamethoxam), a carbamate insecticide (Methiocarb) and a herbicide (Oxadiazon) were tested. The effect of pesticides on estrogen biosynthesis was studied through an ELISA assay using a recombinant form of human aromatase, the enzyme that catalyzes the transformation of androgens to estrogens. Moreover, the effect of pesticides on estrogen signaling was assessed using a gene reporter assay on MELN cells, which measures estrogen receptor-mediated estrogenic activity. The results of the ELISA assay showed that the pesticides did not alter aromatase activity (no interference with estrogen biosynthesis), while the results of the gene reporter assay showed that only Methiocarb was able to alter estrogen signaling at high doses. The estrogenic activity of Methiocarb, expressed as 17β-estradiol equivalency factor (EEF), was equal to 8.0 × 10⁻⁸. In conclusion, this study suggested that Methiocarb should be considered a potential endocrine disruptor.

The alarming human health effects induced by endocrine disruptors (ED) have raised the attention of public opinion and policy makers and have led worldwide to regulations that are continuously improved to reduce exposure to them. However, decreasing the exposure levels is challenging because EDs are ubiquitous and exposure occurs through multiple routes. The main exposure route is considered ingestion, but, recently, the inhalation has been hypothesized as an important additional route. To explore this scenario, some authors applied bioassays to assess the endocrine activity of air. This review summarizes for the first time the applied methods and the obtained evidences about the in vitro endocrine activity of airborne particulate matter (PM) collected outdoor. Among the bioassay endpoints, (anti)oestrogenic and (anti)androgenic activities were selected because are the most studied endocrine activities. A total of 24 articles were ultimately included in this review. Despite evidences are still scarce, the results showed that PM can induce oestrogenic, antioestrogenic, androgenic and antiandrogenic effects, suggesting that PM has an endocrine disrupting potential that should be considered because it could represent a further source of exposure to EDs. Although it is difficult to estimate how much inhalation can contribute to the total burden of EDs, endocrine activity of PM may increase the human health risk. Finally, the results pointed out that the overall endocrine activity is difficult to predict from the concentrations of individual pollutants, so the assessment using bioassays could be a valuable additional tool to quantify the health risk posed by EDs in air.