First insight into in vivo and in vitro biotransformation of 6:2 fluorotelomer carboxylic acid (6:2 FTCA) in zebrafish (Danio rerio)

6:2 fluorotelomer carboxylic acid (6:2 FTCA), as a novel alternative to perfluorooctanoic acid (PFOA), has been widely detected in aquatic environments, while little is known about its bioaccumulation and biotransformation in fish. This study investigated the tissue-specific distribution and biotransformation of 6:2 FTCA in zebrafish during a 21-day exposure in water. The concentration of 6:2 FTCA was highest in the liver, then was in the intestine, gill, brain and muscle. The result consistently indicated that liver was the primary site for 6:2 FTCA biotransformation, subsequently intestine through in vivo and in vitro experiments. 6:2 FTCA experienced similar biotransformation pathway in the liver and intestine and produced 6:2 fluorotelomer unsaturated carboxylic acid (6:2 FTUCA) and C4-C7 perfluorocarboxylic acids (PFCAs) by removing HF, α- and β-oxidation. The significant increase of CYP450 enzyme and the molecular docking results demonstrated that CYP450 enzyme played a crucial role in 6:2 FTCA transformation in the liver. However, in the intestine, beyond CYP450 enzyme, intestinal microbiota also participated the biotransformation of 6:2 FTCA, especially the genera Paracoccus, Gemmobacter and Pelomonas, which could secrete metabolic enzymes and abundance significantly increased after exposure to 6:2 FTCA. This study revealed the potential of the intestine in metabolizing environmental pollutants and provided profound insights into the biotransformation of 6:2 FTCA in aquatic organisms.