John Wiley & Sons, Ltd.

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish)

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Principles of concentration addition (CA) and independent action (IA) have been used as effective tools to predict mixture toxicity based on individual component toxicity. We investigated the toxicity of a pharmaceutical mixture composed of top 10 environmentally detected active pharmaceutical ingredients (APIs) in a relevant concentration ratio. Both individual and mixture toxicities of 10 APIs were evaluated using three short‐term chronic toxicity tests using the alga Pseudokirchneriella subcapitata, daphnid Ceriodaphnia dubia, and zebrafish Danio rerio. With the exception of clarithromycin toxicity to alga, the no observed effect concentration of individual APIs for each test species was dramatically higher than the highest concentration of APIs found in environment. The mixture of 10 APIs resulted in toxicity to alga, daphnid, and fish at 6.25, 100, and 15,000 times higher concentrations, respectively, than that of environmental concentrations of individual APIs. Predictions by CA and IA were nearly identical for alga as clarithromycin was the predominant toxicant in the mixture. Both predictions described the observed mixture toxicity to alga fairly well, whereas they both slightly underestimated the observed mixture toxicity in the daphnid test. In the fish embryo test, the observed toxicity fell between the predicted toxicity by CA and IA. These results suggested that the toxicity of environmentally relevant pharmaceutical mixtures could be predicted by individual toxicity using either CA or IA. This article is protected by copyright. All rights reserved

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