Abstract:Androgens perform a crucial role in the development of vertebrate organisms. Epidemiological statistics show an increasing prevalence of androgen-related diseases. In this research, the combined androgenic effects of 14 herbicides at real environmental ng/L levels were investigated based on a high-throughput androgen receptor reporter gene method, combined with global sensitivity analysis, and compared with the single effects. The results showed that none of the 14 herbicides showed androgenic effects at ambient peak, median, low concentrations, and 5mg/L exposure, but 74% of the herbicides showed significant anti-androgenic activity. More than 90% of the mixtures showed significant anti-androgenic activity, with mixtures 128, 142 and 121 producing more than 50% of the androgenic antagonistic effects. The combined effect of the mixtures was intense and complex. The cumulative concentration of the most effective mixture 128 was 5352.1 ng/L, and the anti-androgenic effect was close to that of the single strongest pollutant, Anilofos (C3), at 5 mg/L. There was no significant relationship between the total herbicide concentrations in the mixture and the anti-androgenic effect. The global sensitivity analysis identified Anilofos (C3), Simetryn (C1), Diuron (C9), and Diflufenican(C2) as the main drivers in the hybrid systems with Simetryn (C1) and Diflufenicanr (C2) is the hidden drivers. This study assesses complex hazard effects of hybrid systems at environmentally relevant concentrations, and the method provides technological support for developing regionally appropriate environmental management policies. In addition, the interactions between the pollutants in the hybrid system should gain more attention.
Keywords:Global sensitivity analysis, Quantitative high-throughput screening,Environmental risk assessment, Combined effect, Anti-androgenic effects