Current understanding of potential ecological risks of retinoic acids and their metabolites in aquatic environments

In animals, retinoic acids (RAs), one of the main derivatives of vitamin A, are crucial for a variety of physiological processes. RAs, including all-trans-RA, 9-cis-RA, 13-cis-RA, and their corresponding metabolites (i.e., all-trans-4-oxo-RA, 9-cis-4-oxo-RA and 13-cis-4-oxo-RA) can be excreted through urination from humans and animals. Sewage treatment plants (STPs) are a significant source of RAs and 4-oxo-RAs into aquatic environments. RAs and 4-oxo-RAs can be identified and quantified by use of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). RAs and 4-oxo-RAs have been reported in various environmental matrices including rivers, lakes, reservoirs and coastal marine environments as well as in sewage effluents discharged from STPs. Greater concentrations of RAs and 4-oxo-RAs have been observed during blooms of cyanobacteria and microalgae, suggesting that cyanobacteria and microalgae are natural sources of RAs and 4-oxo-RAs in aquatic environments. These potential sources of RAs and 4-oxo-RAs raise concerns about their concentrations and risks in aquatic environments because excessive intake of these chemicals can result in abnormal morphological development in animals. Teratogenic effects were observed in amphibians, fish embryos, gastropods, mammals and birds when exposed to RAs. This review summarizes sources, concentrations, adverse effects and ecological risks of RAs and 4-oxo-RAs in aquatic environments. An interim, predicted no-effect concentration (PNEC) of RAs (in terms of at-RA) for freshwater environments was determined to be 3.93 ng/L at-RA equivalents. Based on limited data on concentrations of RAs in freshwater ecosystems, their hazard quotients were found to range from zero to 16.41, depending on the environmental conditions of receiving waters. Ecological risks of RAs in marine environments are yet to be explored due to the paucity of data related to both their concentrations in marine environment and toxic potencies to marine species. This review updates current knowledge of RAs and 4-oxo-RAs in aquatic environments and calls for more studies on their concentrations and fate in aquatic environments, especially estuarine and coastal marine environments with a view to enabling a comprehensive assessment of their ecological risks around the globe. Keywords: Retinoids, Sewage, Cyanobacteria, Aquatic environments, Ecological risks, Marine