Waterborne beclomethasone dipropionate affects the physiology of fish while its metabolite beclomethasone is not taken up

• Published in: The Science of the total environment Vol. 511; pp. 37 - 46
• Main Authors: Carney Almroth, Bethanie M., Gunnarsson, Lina M., Cuklev, Filip, Fick, Jerker, Kristiansson, Erik, Larsson, D.G. Joakim
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2015
• Subjects: Animals; Asthma medicine; Beclomethasone - toxicity; Beclomethasone dipropionate; Biological Sciences; Biologiska vetenskaper; Catalase; Catalase - metabolism; Chemical compounds; Drugs; Environmental risk assessment; Exposure; Farmakologi och toxikologi; Fish; Fishes - physiology; Gene expression; Glucocorticoid; Glucocorticoids - toxicity; Glucose; Glutathione; Glutathione - metabolism; Human; Oncorhynchus mykiss; Pharmacology and Toxicology; Physiology; Rainbow trout; thma medicine; Water Pollutants, Chemical - toxicity; Zoologi; Zoology; Beclomethasone dipropionate; Environmental risk assessment; Asthma medicine; Gene expression; Glucocorticoid; Rainbow trout
• ISSN: 0048-9697; 1879-1026; 1879-1026
• DOI: 10.1016/j.scitotenv.2014.12.016

Asthma is commonly treated with inhalable glucocorticosteroids, including beclomethasone dipropionate (BDP). This is a synthetic prodrug which is metabolized to the more active monopropionate (BMP) and free beclomethasone in humans. To evaluate potential effects of residual drugs on fish, we conducted a 14day flow-through exposure experiment with BDP and beclomethasone using rainbow trout, and analyzed effects on plasma glucose, hepatic glutathione and catalase activity together with water and body concentrations of the BDP, BMP and beclomethasone. We also analyzed hepatic gene expression in BDP-exposed fish by microarray and quantitative PCR. Beclomethasone (up to 0.65μg/L) was not taken up in the fish while BDP (0.65 and 0.07μg/L) resulted in accumulation of both beclomethasone, BMP and BDP in plasma, reaching levels up to those found in humans during therapy. Accordingly, exposure to 0.65μg/L of BDP significantly increased blood glucose as well as oxidized glutathione levels and catalase activity in the liver. Exposure to beclomethasone or the low concentration of BDP had no effect on these endpoints. Both exposure concentrations of BDP resulted in significantly higher transcript abundance of phosphoenolpyruvate carboxykinase involved in gluconeogenesis, and of genes involved in immune responses. As only the rapidly metabolized prodrug was potent in fish, the environmental risks associated with the use of BDP are probably small. However, the observed physiological effects in fish of BDP at plasma concentrations known to affect human physiology provides valuable input to the development of read-across approaches in the identification of pharmaceuticals of environmental concern. •BDP, a commonly used glucocorticoid has physiological effects in rainbow trout exposed via water.•As BDP is expected to be metabolized, environmental risks from excretion are likely to be small.•Effects observed of BDP in fish were similar to effects of corticosteroids observed in man.•Effects were observed at plasma concentrations similar to those reached in humans.•This adds confidence to read-across approaches between humans and fish.