title: Environmental concentrations of anti-androgenic pharmaceuticals do not impact sexual disruption in fish alone or in combination with steroid oestrogens.
abstract: Sexual disruption in wild fish has been linked to the contamination of river systems with steroid oestrogens, including the pharmaceutical 17α-ethinylestradiol, originating from domestic wastewaters. As analytical chemistry has advanced, more compounds derived from the human use of pharmaceuticals have been identified in the environment and questions have arisen as to whether these additional pharmaceuticals may also impact sexual disruption in fish. Indeed, pharmaceutical anti-androgens have been shown to induce such effects under laboratory conditions. These are of particular interest since anti-androgenic biological activity has been identified in the aquatic environment and is potentially implicated in sexual disruption alone and in combination with steroid oestrogens. Consequently, predictive modelling was employed to determine the concentrations of two anti-androgenic human pharmaceuticals, bicalutamide and cyproterone acetate, in UK sewage effluents and river catchments and their combined impacts on sexual disruption were then assessed in two fish models. Crucially, fish were also exposed to the anti-androgens in combination with steroid oestrogens to determine whether they had any additional impact on oestrogen induced feminisation. Modelling predicted that the anti-androgenic pharmaceuticals were likely to be widespread in UK river catchments. However, their concentrations were not sufficient to induce significant responses in plasma vitellogenin concentrations, secondary sexual characteristics or gross indices in male fathead minnow or intersex in Japanese medaka alone or in combination with steroid oestrogens. However, environmentally relevant mixtures of oestrone, 17β-oestradiol and 17α-ethinylestradiol did induce vitellogenin and intersex, supporting their role in sexual disruption in wild fish populations. Unexpectedly, a male dominated sex ratio (100% in controls) was induced in medaka and the potential cause and implications are briefly discussed, highlighting the potential of non-chemical modes of action on this endpoint.
authors: Institute of Environment, Health and Societies, Brunel University, Uxbridge, Middlesex UB8 3PH, UK. Electronic address: christopher.green@brunel.ac.uk.
authors: Christopher
authors: C
authors: Green
authors: Institute of Environment, Health and Societies, Brunel University, Uxbridge, Middlesex UB8 3PH, UK.
authors: Jayne
authors: J
authors: Brian
authors: Institute of Environment, Health and Societies, Brunel University, Uxbridge, Middlesex UB8 3PH, UK.
authors: Rakesh
authors: R
authors: Kanda
authors: Institute of Environment, Health and Societies, Brunel University, Uxbridge, Middlesex UB8 3PH, UK.
authors: Martin
authors: M
authors: Scholze
authors: Centre for Ecology and Hydrology, Wallingford, Oxfordshire OX10 8BB, UK.
authors: Richard
authors: R
authors: Williams
authors: Institute of Environment, Health and Societies, Brunel University, Uxbridge, Middlesex UB8 3PH, UK.
authors: Susan
authors: S
authors: Jobling
mesh_terms: D000726:Androgen Antagonists / Q000032:analysis / Q000633:toxicity*; D000813:Anilides / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D003530:Cyprinidae / Q000502:physiology; D017373:Cyproterone Acetate / Q000032:analysis / Q000633:toxicity*; D012734:Disorders of Sex Development / Q000139:chemically induced; D004958:Estradiol / Q000633:toxicity; D004967:Estrogens / Q000633:toxicity; D004997:Ethinyl Estradiol / Q000032:analysis / Q000633:toxicity; D008297:Male; D009570:Nitriles / Q000032:analysis / Q000633:toxicity*; D009990:Oryzias / Q000502:physiology; D045483:Rivers / Q000737:chemistry*; D012722:Sewage / Q000737:chemistry; D046468:Sexual Development / Q000187:drug effects*; D014105:Tosyl Compounds / Q000032:analysis / Q000633:toxicity*; D014819:Vitellogenins / Q000097:blood; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D004967:Estrogens; D009570:Nitriles; D012722:Sewage; D014105:Tosyl Compounds; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate; D004958:Estradiol; C053541:bicalutamide
keywords: Anti-androgens; Endocrine disruption; Intersex; Mixtures; Predictive modelling; Steroid oestrogens