Bioactive lipids are altered in the heart, kidney, and serum of male and female F344 rats sub-chronically exposed to dietary 2-MCPD

Chloropropanols have been identified as processing-induced food contaminants that occur as by-products of the manufacturing of refined food oils and hydrolyzed vegetable protein. There has been a paucity of research on the 2-monochloropropane-1,3-diol (2-MCPD) isomer, thus forming a data gap for regulatory risk assessment. Previous studies suggest 2-MCPD causes adverse cardiotoxic, nephrotoxic, and myotoxic effects, but were inconclusive for hazard identification ; thus a dose-response OECD TG-408 -compliant study was conducted by Health Canada. Our study profiled the effects of 2-MCPD on oxylipins and oxidized phosphatidylcholines , using HPLC-MS/MS, in heart, kidney, serum, and skeletal muscle of male and female F344 rats orally exposed to 2-MCPD (40 mg/kg BW/d) for 90 days. Cardiac n-3 polyunsaturated fatty acid-derived oxylipins, particularly DHA-derived oxylipins, were lower with 2-MCPD exposure, coincident with cardiac lesions. Lipoxygenase-derived oxylipins were decreased in the serum with a greater effect in the male 2-MCPD treatment group. Few oxylipin alterations were seen in the kidney and there was an absence of alterations in the tibialis anterior. Oxidized phosphatidylcholines and isoprostanes were not altered in this study, indicating that oxidative stress was not elevated by 2-MCPD. These findings add to the weight of the evidence for 2-MCPD toxicity and support the use of serum oxylipins as potential biomarkers of 2-MCPD exposure. • Oxylipin profiles were altered in heart, kidney, and serum of rats exposed to the food contaminant 2-MCPD. • DHA-derived oxylipins were lower in 2-MCPD-exposed hearts, indicating a pro-inflammatory response signature. • 2-MCPD-induced cardiac inflammation was independent of oxidative stress lipid biomarkers (OxPC & isoprostanes). • The oxylipin alterations discovered in the heart provide evidence of their critical role in cardiotoxicity.