Perfluorinated fatty acids (PFCAs), straight chain fatty acid analogues of which all aliphatic hydrogens are substituted with fluorine are primarily used as industrial materials, because of their surfactant properties, and their chemical and thermal stability. 1) Of PFCAs, perfluorooctanoic acid (PFOA) was the most widely used as a reactive intermediate in the industrial synthesis of fluoroacrylic esters, and its salts are used as processing aids in the production of fluoropolymer and fluoroelastmers and in other surfactant use. Since PFOA does not undergo biotransformation 2) and accumulates in the environment, [3][4][5] PFOA is found in the serum of not only occupationally exposed workers, 6) but also general populations. 7,8) In this respect, most efforts have been made to study biological and hazardous effects of PFOA in particular, 9) so that toxicological information pertaining to PFCAs is limited largely to PFOA.The previous studies showed that administration of PFOA markedly induced peroxisomal b-oxidation in the liver of male rats, whereas the induction was observed in female rats to an extremely less extent. 10,11) The subsequent study using rats as experimental animals showed that a sex-related difference in the induction by perfluorononanonic acid (PFNA) and perfluoroheptanoic acid (PFHA) was significant whereas the extent was not so striking as that by PFOA and that perfluorodecanoic acid (PFDA) markedly induced peroxisomal b-oxidation without sex-related difference.12) When compared the potency to induce peroxisomal b-oxidation by among PFHA, PFOA, PFNA and PFDA in the liver of male rats, the potency of the induction has been shown to be in the order of PFHAϽPFOAϽPFNAՅPFDA.12) On the basis of the findings from in vitro experiments employing rat hepatocytes, it is likely that the extent of the induction of peroxisomal b-oxidation by PFCAs depends on only concentration of PFCA molecules rather than the difference in their perfluoroalkyl chain length.12,13) Differed from the case of rats, the administration of PFOA to female mice has been shown to markedly induce peroxisomal b-oxidation in the liver to the extent comparable to that of male mice. 11,14) However, no explanation has been made for the mechanism responsible for this observation. Moreover, little information is available about biological effect of PFCAs other than PFOA in the liver of mice. These facts stimulate our interest in studying the response of the liver to PFCAs with different perfluoroalkyl chain lengths.The specific goals of the present study are to ascertain (i) whether there exists perfluoroalkyl chain length-related difference in response of the liver of mice to PFCAs employing inductions of hepatomegaly, peroxisomal b-oxidation and microsomal 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase as parameters; (ii) the reason why there is no difference in the response of hepatic peroxisomal b-oxidation to PFOA in male and female mice; and (iii) whether there is sex-related difference in the response of hepatic peroxisomal ...