Chronic exposure to PFO4DA and PFO5DoDA, two perfluoroalkyl ether carboxylic acids (PFECAs), suppresses hepatic stress signals and disturbs glucose and lipid metabolism in male mice

Response to Comment on “Novel Perfluoroalkyl Ether Carboxylic Acids (PFECAs) and Sulfonic Acids (PFESAs)”: Overlooked Interactions with Perfluorooctanoic Acid

“…Based on the BMKR model, which was consistent with the multivariate linear regression analysis, we maintain that the results showing the effects of PFO5DoDA on cholesterol and other biochemical parameters are reliable. Recent toxicological evidence further supports our observations, that is, chronic exposure to PFO5DoDA in mice may suppress stress signals and disturb glucose and lipid metabolism in the liver . In addition, the toxicity of PFO5DoDA appears to be stronger than that of PFOA in zebrafish, indicating that PFO5DoDA may be a greater contributor to aquatic toxicity …”

“…Recent toxicological evidence further supports our observations, that is, chronic exposure to PFO5DoDA in mice may suppress stress signals and disturb glucose and lipid metabolism in the liver. 5 In addition, the toxicity of PFO5DoDA appears to be stronger than that of PFOA in zebrafish, indicating that PFO5DoDA may be a greater contributor to aquatic toxicity. 6 We are grateful to Lyu et al for their interest in our article.…”

Environmental Fate of Cl-PFPECAs: Predicting the Formation of PFAS Transformation Products in New Jersey Soils

“…For example, while Cl-PFOS had comparable bioaccumulative potencies and distribution in fish tissues to PFOS, Cl-PFESAs had higher bioaccumulation and longer elimination half-lives in fish, suggesting the presence of an ether oxygen (6:2 Cl-PFESA) or ether oxygen and additional perfluorinated carbons (8:2 Cl-PFESA) may pose an even greater threat to organisms than the well characterized legacy PFOS or a single chlorine-substituted PFOS . Similarly, a study on potential bioaccumulation and health risks of perfluoroalkyl ether carboxylic acids (PFPECAs) in mice concluded increased health risks including suppressed stress signals and disturbed glucose and lipid metabolism in the liver following exposure . Furthermore, a comparison of two structurally similar PFPECAs, differing only by a single −OCF 2 – result in dramatically different toxicokinetic and elimination rates in mice, with predominant distribution in the liver (in relation to serum concentrations) for perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoDA) compared to perfluoro-3,5,7,9-butaoxadecanoic acid (PFO4DA) and PFOA, suggesting greater internal dose and potential subsequent adverse effects in the liver in the case of the PFPECA with the ether linkage …”

Occurrence of Novel Perfluoroalkyl Ether Carboxylic Acids in River Water and Human Urine Quantified by a Simple Liquid–Liquid Microextraction Approach Coupled with LC–MS/MS

“…4,13−15 Long-chain homologues have been detected in human sera, 4,16,17 and their levels are significantly associated with lipid and liver function biomarkers. 17 Evidence also suggests that the hepatotoxicity 18 and developmental toxicity 19 of these long-chain PFECAs may be more serious than those of PFOA.…”

“…Some of these PFECAs are found at comparable or even greater levels than historical PFASs in field studies downstream of fluorochemical plants. ,− Long-chain homologues have been detected in human sera, ,, and their levels are significantly associated with lipid and liver function biomarkers . Evidence also suggests that the hepatotoxicity and developmental toxicity of these long-chain PFECAs may be more serious than those of PFOA.…”