The Carbon Number‐specific Impact of Mineral Oil Saturated Hydrocarbons on Inducing Colonic Inflammation in Female and Male Fischer 344 Rats

ABSTRACT This study investigated the effects of mineral oil saturated hydrocarbon (MOSH) sub‐fractions (C 20‐30 and C 30‐50 ) on the colon of male and female F344 rats and the underlying mechanisms. Due to its specific accumulation in the colon, the C 20‐30 sub‐fraction, particularly at a high dose (15 g/kg), elicited mucosal epithelial detachment and loss of intestinal glands in both sexes after 6 months of exposure. These pathological changes were accompanied by corresponding shifts in biomarkers indicative of increased inflammation (IL‐1β, IL‐2, TNF‐α), oxidative stress (SOD, MDA), and impaired tight junction function (ZO‐1, claudin‐1, occludin), potentially mediated by the suppression of the Keap1/Nrf2 signaling pathway. Fecal metabolomics further revealed that exposure to either sub‐fraction altered metabolites and metabolic pathways in a sex‐ and dose‐dependent manner. The most significantly enriched differential pathways were cysteine and methionine metabolism in females and glutathione metabolism in males. Collectively, these findings provide new evidence for the colon‐specific risks of MOSH sub‐fractions.