title: Chronic effects assessment and plasma concentrations of the beta-blocker propranolol in fathead minnows (Pimephales promelas).
abstract: The presence of many human pharmaceuticals in the aquatic environment is now a worldwide concern, yet little is known of the chronic effects that these bioactive substances may be having on aquatic organisms. Propranolol, a non-specific beta adrenoreceptor blocker (beta-blocker), is used to treat high blood pressure and heart disease in humans. Propranolol has been found in surface waters worldwide at concentrations ranging from 12 to 590ng/L. To test the potential for ecologically relevant effects in fish in receiving waters, short-term (21 days) adult reproduction studies were conducted, in which fathead minnows were exposed to nominal concentrations of propranolol hydrochloride [CAS number 318-98-9] ranging from 0.001 to 10mg/L (measured concentrations typically from 78 to 130%). Exposure of fish to 3.4mg/L (measured) over 3 days caused 100% mortality or severe toxicity requiring euthanasia. The most sensitive endpoints from the studies were a decrease in hatchability (with regard to the number of days to hatch) and a concentration-related increase in female gonadal somatic index (GSI), giving LOEC(hatchability) and LOEC(female GSI) values of 0.1mg/L. Concentration-related decreases in weights of male fish were also observed, with LOEC(male wet weight value) of 1.0mg/L, and the LOEC(reproduction) value was 1.0mg/L. Collectively, these data do not suggest that propranolol was acting as a reproductive toxin. Plasma concentrations of propranolol in male fish exposed to nominal concentrations of 0.1 and 1.0mg/L were 0.34 and 15.00mg/L, respectively, which constitutes 436 and 1546% of measured water concentrations. These compare with predicted concentrations of 0.07 and 0.84mg/L, and thus to a degree support the use of partition coefficient models for predicting concentrations in plasma in fish. In addition, propranolol plasma concentrations in fish exposed to water concentrations of 0.1 and 1.0mg/L were greater than the human therapeutic plasma concentration and hence these data very strongly support the fish plasma model proposed by Huggett et al. [Huggett, D.B., Cook, J.C., Ericson, J.F., Williams, R.T., 2003a. A theoretical model for utilizing mammalian pharmacology and safety data to prioritize potential impacts of human pharmaceuticals to fish. Hum. Ecol. Risk Assess. 9, 1789-1799].
authors.affiliation: Institute for the Environment, Brunel University, Uxbridge, Middlesex, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Giltrow
authors.forename: Paul D
authors.initials: PD
authors.lastname: Eccles
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Winter
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McCormack
authors.forename: Mariann
authors.initials: M
authors.lastname: Rand-Weaver
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hutchinson
authors.forename: John P
authors.initials: JP
authors.lastname: Sumpter
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D000818:Animals; D049628:Body Size / Q000187:drug effects; D003530:Cyprinidae / Q000502:physiology*; D005260:Female; D008297:Male; D009929:Organ Size / Q000187:drug effects; D052287:Oviparity / Q000187:drug effects; D011433:Propranolol / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D012098:Reproduction / Q000187:drug effects*; D016019:Survival Analysis; D014867:Water / Q000737:chemistry; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D015053:Zygote / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D014874:Water Pollutants, Chemical; D014867:Water; D011433:Propranolol