As the application and environmental release of tris(1,3-dichloro-2-propyl)
phosphate (
TDCIPP) are being increased rapidly, serious concerns have been raised regarding its adverse effects on human health. Exposure to
TDCIPP has been implicated in hepatotoxicity, but the molecular mechanisms remain unclear. Here, both male and female Sprague Dawley rats were administered
TDCIPP with 125, 250, or 500 mg/kg/day for 12 weeks. Then the ultrastructure of liver, biochemical indicators in serum and liver, and hepatic gene expression were analyzed to reveal molecular mechanisms of hepatotoxicity induced by
TDCIPP. Continuous
TDCIPP exposure decreased
body weight, particularly in 500 mg/kg/day
TDCIPP-exposed males, and dose dependently increased the ratio of liver to
body weight in both genders. The decreased levels of
triglyceride,
cholesterol, and
transaminase in the serum and livers were observed in both genders after
TDCIPP exposure, which indicated dysfunction in the hepatic metabolism. Liver histopathology revealed hepatocellular damages in males and females after
TDCIPP exposure. The transcriptomic analysis indicated that
TDCIPP exposure significantly changed pathways of
bile acid metabolism, inflammatory response, oxidative phosphorylation and carcinogenicity in 250 and 500 mg/kg/day
TDCIPP-exposed males and 500 mg/kg/day
TDCIPP-exposed females, and there was no statistical significance in any other
TDCIPP-exposed groups. The transcriptional analysis showed that
TDCIPP exposure led to oxidative stress in the livers of rats, thereby increasing the inflammatory response and promoting mechanisms of
carcinogenesis in both genders. Finally,
TDCIPP led to more severe adverse phenotypic effects in male than female rats.