Elimination and Toxicity of Perfluorooctanoic Acid during Subchronic Administration in the Wistar Rat

Abstract

Perfluorinated fatty acids have been used commercially as corrosion inhibitors, wetting agents, five extinguishers and surface active agents. In an earlier study the male rats were more susceptible to the toxic effects of perfluorooctanoic acid (PFO) than females. PFO-concentrations in the plasma suggested that there was a sex related difference in the urinary elimination rate. Active tubular secretion was observed only in the female kidney. The aim of the present study was to compare the urinary elimination of PFO between the two sexes during subchronic administration to the Wistar rat. PFO was administered by gavage to 48 newly-weaned animals at 0 mg/kg, 3 mg/kg, 10 mg/kg and 30 mg/kg for 28 consecutive days. The urine was collected on the 7th and 28th day of the study. At the end of the study, blood was collected by cardiac puncture. At necropsy, tissue specimens for histopathologic examination were collected from the controls and from the group receiving 30 mg/kg of PFO daily. Unlike the female rats, on the 7th day of the study all three groups of male rats excreted significant less PFO than their daily dose of PFO, which suggested that the males had not reached a steady state by seven days. On the 20th day, the males excreted an amount of PFO equal to their daily dose. The PFO concentrations in the plasma of the male animals suggested that the binding sites of PFO may become saturated at the chronic daily dose level of 30 mg/kg. Although the PFO concentrations in the plasma were significantly higher in the male animals, no significant differences were observed at necropsy or in a histopathological findings between the sexes.