Effects of the anti-androgen, bicalutamide, in a reduced life-cycle study with the fathead minnow (Pimephales promelas)

Abstract

In support of the environmental risk assessment (ERA) of the non-steroidal anti-androgen bicalutamide, a reduced fish full life-cycle (FFLC) was conducted. The traditional FFLC is deemed to be the “gold standard” for evaluating the potential environmental impact of human pharmaceuticals, covering all life-stages and measuring long term effects. However, such studies require large numbers of animals and take considerable effort and time. The reduced FFLC, employed here, used fewer animals and was shorter in duration, yet still included sensitive life-stages and measured long term effects to provide robust information in support of the ERA for an endocrine disrupting chemical. Fathead minnows (Pimephales promelas) were held in breeding pairs and their reproductive performance assessed over 28 days. Embryos from at least two pairs per treatment were subsequently grown up until 85 days post hatch and a subset allowed to spawn to assess the developmental and reproductive effects of the parental exposure on this F1 generation. Fish were exposed in a flow-through system, at 25±1°C. Nominal (mean measured) test concentrations of bicalutamide were 0.01 (0.055), 0.10 (0.10), 1.0 (0.9), 10 (9.2) and 100 (92.1)μgL−1. There were no significant effects on F0 fecundity or growth (wet weight and standard length), but a significant decrease in nuptial tubercle prominence (a secondary sexual characteristic, SSC) was observed in male fish exposed to 100μgL−1. In the F1 generation, there were no treatment-related effects on hatching success or SSC, but survival was significantly decreased in fish exposed to the top concentration (100μgL−1). In female fish, wet weight and standard length were also significantly increased at this concentration. Gonadal histopathology revealed no treatment related effects on sex ratio, sexual differentiation or sexual development. However, there was a concentration related effect on gonad lesion severity in female fish exposed to 100μgL−1 and reproduction (number of eggs spawned) was also significantly reduced in breeding groups exposed to this concentration. Taking into account these data, the overall no observed effect concentration and lowest observed effect concentration values for bicalutamide were 10 and 100μgL−1, respectively.