Selected widely prescribed pharmaceuticals: toxicity of the drugs and the products of their photochemical degradation to aquatic organisms.

Cholesterol-lowering drugs, antidiabetics, antiarrhythmics, antidepressants, and antibiotics belong to the most prescribed drugs worldwide. Because of the manufacture, excretion, and improper disposal of leftover drugs, the drugs enter waste waters and, subsequently, surface waters. They have been detected in surface waters all over the world, from concentrations of ng/l to concentrations several orders of magnitude higher. Since pharmaceuticals are designed to be both biologically and chemically stable, photochemical degradation by sun radiation represents a way of transformation in the natural environment. This review provides a survey of how selected drugs of the above-mentioned classes affect aquatic organisms of different trophic level. The emphasis is on the harmful effects of phototransformation products, an area of scientific investigation that has only attracted attention in the past few years, revealing the surprising fact that products of photochemical degradation might be even more toxic to aquatic organisms than the parent drugs.

Photodegradation of fluoroquinolones in aqueous solution under light conditions relevant to surface waters, toxicity assessment of photoproduct mixtures.

Photochemical degradation of fluoroquinolones ciprofloxacin, enrofloxacin and norfloxacin in aqueous solution under light conditions relevant to surface waters at neutral and alkaline pH was found to proceed readily with half-lives between 0.9 and 2.7 min. The products of photochemical degradation identified by HPLC-MS included defluorinated, hydroxylated, and decarboxylated structures as well as structures with opened cyclic structures. For all of the studied substances, the reaction pathways were influenced significantly by the pH of the reaction system, with more products formed at alkaline pH than at neutral pH: the ratios of products in neutral and alkaline pH were 16/26, 9/19, 15/23 for ciprofloxacin, enrofloxacin, and norfloxacin, respectively. The structures of photoproducts and pathways of photochemical degradation are proposed. The antibacterial activities of photoproduct mixtures tested on E. coli and S. epidermidis were significantly higher in comparison to parental antibiotics in the case of both ciprofloxacin and enrofloxacin with p-values less than 0.0001 in most cases. The effect of the photoproducts was shown to be dependent on the pH value of the original antibiotic solutions before photodegradation: for ciprofloxacin, antibacterial activity against E. coli was more notably pronounced with regard to neutral pH photoproducts, while a less significant, or in one case not significant, effect of pH was observed against S. epidermidis; for norfloxacin, antibacterial activity against both E. coli and S. epidermidis was especially high with regard to alkaline pH photoproducts.

Toxicity assessment of verapamil and its photodegradation products.

Pathways of photochemical degradation of a cardiovascular drug verapamil under conditions relevant to natural waters and the toxicity of the photoproducts to Daphnia magna were investigated. Photodegradation was shown to proceed via photocatalysed mechanism. Two main photodegradation pathways were recognised: the first leading to hydroxylation at the methylamino position followed by splitting of verapamil molecule into two fragments, and the second providing the main active metabolite of verapamil, norverapamil, and a series of norverapamil isomers, followed again by their splitting at the amino group position. Twenty-two products of photodegradation were identified. Toxicity assays in sublethal concentrations of the parental drug, of the photoproduct mixture, and of norverapamil revealed no direct negative response in Daphnia magna to verapamil. On the other hand, photochemical products significantly lowered the number of juveniles, number of clutches, and body size of Daphnia. The exposition of Daphnia to norverapamil showed the same but even more pronounced effects than its exposition to the mixture of photoproducts, which leads to the conclusion that norverapamil is mainly responsible for the toxicity of photoproduct mixture and represents a noteworthy threat to aquatic invertebrates.