Preliminary risk assessment of the lipid-regulating pharmaceutical clofibric acid, for three estuarine species

Clofibric acid is the active metabolite of several fibrate drugs prescribed to reduce blood cholesterol levels. It is persistent and widely detected in the environment. Clofibric acid toxicity was assessed using three estuarine organisms: an alga (Dunaliella tertiolecta), a crustacean (Palaemonetes pugio), and a fish (Fundulus heteroclitus). Mortality and sublethal physiological responses (protein, lipid, cholesterol, and cytochrome P450 levels) were examined. Clofibric acid did not significantly affect cell density or growth rate of D. tertiolecta (concentrations 1000 μg/L). Survival of P. pugio and F. heteroclitus were also unaffected at clofibric acid concentrations 1000 μg/L. In addition, no significant changes in the sublethal test endpoints were found. An additional chronic (17-day) exposure of F. heteroclitus to clofibric acid (10 μg/L) was conducted and found no effects on survival or sublethal endpoints. The rabbit polyclonal CYP450 4A antibody did cross react with F. heteroclitus, demonstrating that a CYP4A-like isoform is present in this teleost species and may be used in future induction studies. Clofibric acid, however, did not alter CYP4A levels in F. heteroclitus. Measured concentrations in the environment have not exceeded 10 μg/L. Therefore, the results of this study indicate a low risk of adverse effects from environmental exposure to clofibric acid for the species tested.