Considering enantiospecific effects of chiral pharmaceutical contaminants to model aquatic organisms: Effects on behavioral, physiological, and traditional toxicity testing endpoints.

摘要

In the present study, enantiospecific effects of chiral contaminants were explored using two chiral pharmaceutical contaminants as model compounds. These compounds are the selective serotonin reuptake inhibitor antidepressant fluoxetine and the beta-adrenergic receptor blocking agent propranolol. An aquatic invertebrate, Daphnia magna, and an aquatic vertebrate, Pimephales promelas, were used as model organisms. In addition to commonly used standardized bioassay endpoints, effects of these compounds were also assessed using nontraditional sublethal endpoints that were specifically chosen to target the known modes of action of the model pharmaceuticals. These include D. magna heart rate and grazing rate and P. promelas feeding rate, swimming performance, and swimming behavior. Known enantiospecific differences in activity of propranolol and fluoxetine in mammals were compared with enantiospecific differences in their toxicity to aquatic organisms. Results indicate that mammalian pharmacology data on enantiospecific effects are more predictive of enantiospecific toxicity in aquatic vertebrates than invertebrates for the two drugs tested. The results presented here also demonstrate that mode-of-action-targeted endpoints should be considered for pharmaceuticals as they can be more sensitive than traditional endpoints, show enantiospecific and sex-specific effects, and provide information on highly ecologically relevant biological processes such as feeding. A summary of the current regulatory provisions for chiral contaminants is made along with the author's recommendations for the improvement of the assessment of environmental risk for chiral contaminants.