Effects of pharmaceutical pollutants and their mixtures on aquatic organisms – with particular focus on reproduction and endocrine function in a fish model species.

Abstract

A number of pharmaceuticals have been shown to have adverse effects on key biological processes of aquatic organisms at low concentrations (ng/l range). Key questions for chemical risk assessment are whether such pharmaceuticals can produce adverse effects on organisms when present in the environment in combination and at low concentrations, whether these can be classified as additive, and under what circumstances can they be predicted. The main purpose of this study was to assess the potential for combination effects of a multicomponent steroid pharmaceutical mixture of dissimilarly acting compounds on an ecologically relevant end point – reproduction, using the existing predictive toxicity models Concentration Addition (CA) and Independent Action (IA). Concentrations of steroids close to those reported in the environment were shown to produce adverse effects on reproduction when present in combination with other steroids. Clear combination effects significantly larger than the effects of the individual compounds were observed when each compound was present at a concentration below the detection limit of the assay, demonstrating a ‘something from nothing’ mixture effect. Furthermore, IA predicted more pronounced effects on egg production that CA, an observation previously unreported from the literature. Actual observed effects were closer to the IA prediction. Additional biomarker and molecular endpoints were examined in subsequent studies to establish the mechanisms of disrupted reproduction in pair-breeding FHMs exposed to the steroid mixture. Results from this study indicate that reproductive impairment of fish exposed to the steroid mixture is likely due to the masculinisation of female fish due to the androgenic activity of the mixture. These results have implications for chemical risk assessment, and in particular, highlight the need for caution when using CA as a worst-case approximation of mixture effects.