Pharmaceuticals in the environment: The effects of clofibric acid on fish

Abstract

Pharmaceuticals in the aquatic environment is an emerging issue and the risks they pose are mostly unknown. They are used in large amounts throughout the world and can enter the environment, as the active metabolite or unmetabolised, through excretion by people and improper disposal. As these drugs are designed to have specific biological effects in a specific organism (as well as sometimes having other non-specific side effects), their potential to cause effects within the environment is great. Clofibric acid (the major metabolite of the lipid lowering drug, Clofibrate) is non-biodegradable, highly motile, very persistent and frequently detected at μg/I levels in the environment. I studied possible effects of clofibric acid in fish, using different experimental approaches and endpoints. The studies involve two different species, and for one of these species, fish at different stages of development. The chapters within this thesis have presented the first evidence (albeit preliminary) of clofibric acid having effects on both adult and embryo fish. When fathead minnow embryos were exposed to clofibric acid, the effects seen included changes in the eggshell, time to hatch, hatchability, mortality and viability. Adult fathead minnow were similarly exposed and significant effects on specific parameters were also observed. These included effects on lipid metabolism, steroidogenesis and spermatogenesis - thought to be via cholesterol transport - as well as significant effects on the expression of several genes involved in lipid metabolism and detoxification. Exposure of juvenile (sexually undifferentiated) bream also found significant differences in some endpoints. Other results suggested, less pronounced effects of clofibric acid on some other parameters. The results from this research show that there are effects of clofibric acid in pathways which were not only unexpected in fish (for example, steroidogenesis, spermatogenesis and gene expression), but also at concentrations below those previously shown to have any biological effects on fish. These effects indicate that clofibric acid may potentially have an impact on fish fecundity, and even more worryingly, on human health for those people prescribed it.