Toxic Effects On Aquatic Organisms And Ecological Risks Of Chiral Pharmaceutical Ibuprofen

Chirality is a stereo-structural property of a compound,where a chiral molecule has a pair of enantiomers that are mirror images of each other and are not able to completely overlap.In general,the two enantiomers of a chiral pharmaceutical have the same physicochemical properties,but are stereoselective in their interactions with enzymes,receptors or other chiral molecules,resulting in different biological responses in terms of pharmacodynamics,toxicology and metabolism kinetics.Over 56% of the pharmaceuticals currently produced and used worldwide are chiral pharmaceuticals,and upon entering the surface water environment,the 2 enantiomeric isomers may differ significantly in terms of biodegradation and ecotoxicity,posing varying degrees of ecological risk.Ibuprofen is a non-steroidal chiral pharmaceutical used for pain relief and antiinflammatory purposes,with 2 enantiomers,R-ibuprofen and S-ibuprofen,and a 1:1mixture of racemates in clinical use.Toxicity exposure tests on three common aquatic organisms showed that R-ibuprofen was the most toxic for growth inhibition of nontuned isinglass meiosis,while S-ibuprofen was the most toxic for reproduction inhibition of calyx brachyurans,with the intensity of the toxic effect of the racemate lying between the 2 enantiomers.Toxicity exposure experiments with Daphnia magna revealed that S-ibuprofen caused a significant increase in the number of Daphnia magna produced and had a pro-reproductive effect on Daphnia magna,while R-ibuprofen had an inhibitory effect.There were some differences in the effects of the two ibuprofen enantiomers on the redox system of Daphnia magna,with R-ibuprofen being more toxic to Daphnia magna compared to S-ibuprofen.In vitro experiments with yeast cells revealed that S-ibuprofen had estrogen receptor-inducing and androgen receptorinhibiting effects,which promoted Daphnia magna reproduction and increased its Daphnia magna production,while R-ibuprofen had estrogen receptor-inhibiting effects,which inhibited Daphnia magna reproduction and decreased its Daphnia magna production.In Beijing surface water,the detection rate of ibuprofen was 96.8%,with concentrations ranging from 0 to 431.7 ng/L,dominated by S enantiomers,and the ratio of total ibuprofen concentrations ranged from 0.57 to 1.Risk quotient(RQ)was used to assess the risk,and 21 sites were found to be of high risk(RQ>10)and 9 sites were of medium risk(10<RQ<1).A probabilistic risk assessment based on the most sensitive toxicity indicator of all species gave a probability of 99.42% that ibuprofen would cause effects to 5% of aquatic organisms,which is a medium risk.Considering the predominance of S-ibuprofen in surface waters,the PNEC derived based on Sibuprofen toxicity data is higher than that of racemates and therefore the ecological risk of ibuprofen should be slightly lower in the actual water environment.