Bioaccumulation and biotransformation of the beta-blocker propranolol in multigenerational exposure to Daphnia magna

Abstract

Multigenerational bioaccumulation and biotransformation activity and short-term kinetics (e.g., uptake and depuration) of propranolol in Daphnia magna were investigated at environmental concentration. The body burden and the major metabolite, desisopropyl propranolol (DIP), of propranolol were quantified using LC-MS/MS at the end of each generation after exposure for 11 generations. The accumulation of propranolol in D. magna at an environmental concentration of 0.2 μg/L was not much different between the parent (F0) and the eleventh filial (F10) generation. However, at 28 μg/L, its accumulation was 1.6 times higher-up to 18.9 μg/g-in the F10 generation relative to the F0. In contrast to propranolol, DIP intensity gradually increased from F0 to F10 at 0.2 μg/L, reflecting an increase in detoxification load and biotransformation performance; no increasing trend was observed at 28 μg/L. The bioaccumulation factor (BAF) showed higher values with a lower concentration and longer period of exposure. The average values of the BAF for 21 days of long-term exposure in successive 11 generations were 440.4 ± 119.7 and 1026.5 ± 208.6 L/kg for 28 μg/L and 0.2 μg/L, respectively. These are comparable to the BAF of 192 for the short-term 72-h exposure at 28 μg/L in the parent generation. It is also recommended that future studies for pharmaceutical ingredients be conducted on drug-drug interaction and structural characteristics on the prediction of biotransformation activity and bioaccumulation rate.

Keywords: Bioaccumulation; Biotransformation; Daphnia magna; Multigeneration; Propranolol.