RRC ID 37332
Author Watanabe H, Tamura I, Abe R, Takanobu H, Nakamura A, Suzuki T, Hirose A, Nishimura T, Tatarazako N.
Title Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish).
Journal Environ Toxicol Chem
Abstract Principles of concentration addition and independent action have been used as effective tools to predict mixture toxicity based on individual component toxicity. The authors investigated the toxicity of a pharmaceutical mixture composed of the top 10 detected active pharmaceutical ingredients (APIs) in the Tama River (Tokyo, Japan) in a relevant concentration ratio. Both individual and mixture toxicities of the 10 APIs were evaluated by 3 short-term chronic toxicity tests using the alga Pseudokirchneriella subcapitata, the daphnid Ceriodaphnia dubia, and the 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 the environment. The mixture of 10 APIs resulted in toxicity to alga, daphnid, and fish at 6.25 times, 100 times, and 15,000 times higher concentrations, respectively, than the environmental concentrations of individual APIs. Predictions by concentration addition and independent action 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 slightly underestimated the observed mixture toxicity in the daphnid test. In the fish embryo test, the observed toxicity fell between the predicted toxicity by concentration addition and independent action. These results suggested that the toxicity of environmentally relevant pharmaceutical mixtures could be predicted by individual toxicity using either concentration addition or independent action.
Volume 35(4)
Pages 996-1006
Published 2016-4-1
DOI 10.1002/etc.3285
PMID 26472177
MeSH Animals Aquatic Organisms Chlorophyta / drug effects* Cladocera / drug effects* Drug-Related Side Effects and Adverse Reactions* Embryo, Nonmammalian Japan No-Observed-Adverse-Effect Level Risk Assessment / methods Rivers / chemistry Toxicity Tests, Chronic Water Pollutants, Chemical / toxicity* Zebrafish*
IF 3.152
Times Cited 37
Algae NIES-35