The acute toxicity of perfluorooctanoic and perfluorodecanoic acids in male rats and effects on tissue fatty acids.

The acute toxicities of single ip injections of perfluorooctanoic (PFOA) and perfluorodecanoic (NDFDA) acids were evaluated in male Fischer rats. The LD50/30 day for PFOA was 189 (208-175) mg/kg and for NDFDA was 41 (47-34) mg/kg. All rats treated with lethal doses of PFOA died within the first 5 days; with NDFDA there was delayed lethality, with deaths in the second and third weeks after dosing. Four groups of rats were used for a more detailed study of toxicity and for analysis of fatty acids from liver, testes, and whole blood. One group received a single dose of 100 mg PFOA/kg; a second, a single dose of 2 ml of propylene glycol-water (1:1)/kg (vehicle control); a third, a single dose of 50 mg NDFDA/kg; the fourth was given 2 ml vehicle/kg and pair-fed with the NDFDA group. The first three groups were fed ad libitum. Rats from each group were killed at 2, 4, 8, and 16 days after dosing for fatty acid analysis. Rats dosed with NDFDA lost half their body weight in 16 days and ate virtually no food from Day 7 to Day 14 after dosing. Weight loss was less rapid in pair-fed controls. With PFOA there were transient decreases in food intake and body weight which were reversed by Day 7. Liver weights of PFOA rats were slightly greater than those from vehicle controls. With NDFDA, liver weights were much greater than those from pair-fed controls. In the livers of PFOA rats there were transient increases in oleic and palmitic acids and a decrease in stearic and docosahexaenoic acids. These changes were maximum by Day 2 and nearly resolved by Day 8. With NDFDA, similar changes were observed and arachidonic acid was also greatly decreased. These changes were quantitatively much larger and more persistent. NDFDA has unusually high toxic potency for a perfluorinated hydrocarbon, and some of the toxic effects caused by this acid are remarkably similar to those seen with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The acute toxicity of NDFDA may be due to an ability to interfere with fatty acid metabolism, and studies of its toxicity may be valuable in helping to understand mechanisms of action of TCDD.