title: Preliminary studies into the effects of the human pharmaceutical Clofibric acid on sperm parameters in adult Fathead minnow.
abstract: The effects of Clofibric acid (a persistent environmental metabolite of Clofibrate, a human pharmaceutical), on Fathead minnows were studied. Fibrates are used to prevent cardiovascular disease through their antilipidemic activity. In a series of experiments, in which fish were exposed to waterborne Clofibric acid, no convincing, reproducible antilipidemic effects were observed. In contrast, in three separate experiments, Clofibric acid affected the reproductive axis of fish. Spermatogenesis was apparently impaired, leading to a marked reduction in sperm count in two of the three experiments. Various measures of sperm motility were also reduced, although only significantly so at the highest concentration of Clofibric acid tested (1mg/L). There were also indications that plasma androgen concentrations were reduced. These effects of Clofibric acid on the reproductive axis of fish are similar to those that occur in some mammals as a side-effect of the drug. Taken together, a weight-of-evidence argument would suggest that the main discernable effect of Clofibric acid on fish is likely to be a reproductive, not an antilipidemic, one. Although some of these reproductive effects of Clofibric acid occurred only at a high concentration (1mg/L), others occurred at lower concentrations (microg/litre), near or similar to those reported in the aquatic environment (ng to low microg/litre range). Although we recognise that this is not a definitive study of the effects of Clofibric acid on fish reproduction, the results strongly suggest that Clofibric acid could adversely affect sperm parameters and androgen concentrations in adult Fathead minnows. Further studies are warranted. This may be an example of a drug in which an accidentally discovered side-effect found in mammals turns out to be the most important effect in a different vertebrate group, namely fish.
authors.affiliation: Institute for the Environment, Brunel University, Uxbridge, Middlesex UB8 3PH, UK. Tamsin.Runnalls@Brunel.ac.uk
authors.forename: Tamsin J
authors.initials: TJ
authors.lastname: Runnalls
authors.forename: David N
authors.initials: DN
authors.lastname: Hala
authors.forename: John P
authors.initials: JP
authors.lastname: Sumpter
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D002995:Clofibric Acid / Q000633:toxicity*; D003530:Cyprinidae / Q000097:blood / Q000502:physiology*; D005260:Female; D000960:Hypolipidemic Agents / Q000633:toxicity*; D008297:Male; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects*; D013739:Testosterone / Q000031:analogs & derivatives / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000960:Hypolipidemic Agents; D014280:Triglycerides; D014874:Water Pollutants, Chemical; D013739:Testosterone; D002995:Clofibric Acid; D002784:Cholesterol; C003600:11-ketotestosterone