Study on the variety of the effects of perfluorinated fatty acids on biological systems and the biological mechanisms for identification of each molecules.

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The effects of perfluorinated fatty acids (PFCAs) having 7-10 carbon atoms were compared in rats. PFCAs having 8-10 carbon atoms lowered serum levels of lipids. PFCA having 9 and 10 carbon atoms caused accumulation of lipid droplets in the liver and renal proximal tubular cells in rats.In the liver of rats treated with PFCA having 10 carbon atoms, fatty acid synthesis and β-oxidation was accelerated whereas secretion of VLDL was suppressed. Therefore, the accumulation of triglyceride (TG) is thought to be, at least partly, due to suppression of VLDL secretion and acceleration of fatty acid synthesis.When the potency of the induction of peroxisomal β-oxidation and accumulation of TG in rat liver was compared, PFCA having longer carbon chain length was more potent. Sex-related difference was observed in the effects of PFCAs having 8 and 9 carbon atoms. There are highly significant correlations between hepatic concentrations of PFCA and the activity of peroxisomal β-oxidation or hepatic TG content regardless of the carbon chain length of PFCA, suggesting that difference in the accumulation in liver is responsible for the difference in the potency of the induction of peroxisomal β-oxidation and TG accumulation in rats. Essentially the same result was obtained from mice.PFCA having shorter carbon chain length was more quickly excreted into urine. Female rats excreted PFCA faster than male rats. By contrast, excretion rates of PFCAs in feces were slow compared to those of urine and there was no significant difference between PFCAs having different carbon chain length and between sexes. Urinary excretion rate was regulated by testosterone in male rats. The results indicate that the difference in the accumulation between PFCAs having 7-9 carbon atoms is due to difference in the rate of urinary excretion, which is regulated by testosterone.