Tissue toxicokinetics of perfluoro compounds with single and chronic low doses in male rats

抄録

To examine the kinetics of low doses of perfluoro compounds (PFCs), we administered perfluorohexanoic acid (C6A), perfluorooctanoic acid (C8A), perfluorononanoic acid (C9A) and perfluorooctane sulfonate (C8S) with a single oral dose (50-100 μg/kg BW), and in drinking water at 1, 5, and 25 μg/L for one and three months to male rats; and examined the distribution in the brain, heart, liver, spleen, kidney, whole blood and serum. C6A was very rapidly absorbed, distributed and eliminated from the tissues with nearly the same tissue t_1/2 of 2-3 hr. Considering serum Vd, and the tissue delivery, C6A was mainly in the serum with the lowest delivery to the brain; and no tissue accumulation was observed in the chronic studies as estimated from the single dose study. For the other PFCs, the body seemed to be an assortment of independent one-compartments with a longer elimination t_1/2 for the liver than the serum. The concentration ratio of liver/serum increased gradually from C₀ to a steady state. The high binding capacity of plasma protein may be the reason for the unusual kinetics, with only a very small fraction of free PFCs moving gradually to the liver. Although the tissue specific distribution was time dependent and different among the PFCs, the Vd and k_e of each tissue were constant throughout the study. The possibility of extremely high C6A accumulation in the human brain and liver was suggested, by comparing the steady state tissue concentration of this study with the human data reported by Pérez et al. (2013).