Tissue distribution and hepatic subcellular distribution of perfluorooctanoic acid at low dose are different from those at high dose in rats

Abstract

Fate of perfluorooctanoic acid (PFOA) after an intravenous injection to male rats at the dose of 0.041 mg/kg body weight was compared with that at the dose of 16.56 mg/kg body weight. In the liver, 52% and 27% of PFOA dosed was recovered 2 h after an intravenous injection at the low and the high doses, respectively. By contrast, larger proportion of PFOA dosed was distributed to serum, other tissues and carcass at the high dose compared with the low dose. Subcellular distribution of PFOA was determined in the liver. At the dose of 0.041 mg/kg, 45%, 34%, 18% and 3% were distributed to 8000 g pellet, 18000 g pellet, 105000 g pellet and 105000 g supernatant fraction, respectively; 28%, 17%, 13% and 43% of PFOA were distributed to these fractions, respectively, at the dose of 16.56 mg/kg. The higher the concentration of hepatic PFOA was, the more the PFOA was distributed to 105000 g supernatant fraction. Biliary excretion index increased as PFOA concentration raised in the liver. These results suggest that PFOA is preferentially taken-up by the liver, and distributed to membrane fractions, especially 18000 g pellet, and hardly excreted into bile when exposed at very low dose. © 2007 Pharmaceutical Society of Japan.