Pathological and Hepatic Ultrastructural Effects of a Single Dose of Perfluoro-n-decanoic Acid in the Rat, Hamster, Mouse, and Guinea Pig

In rats, the liver is the primary target organ of perfluoro-n-decanoicacid (PFDA) toxicity. Therefore, the effects of PFDA on hepaticultrastructure were studied in rats. Pathological changes inducedby PFDA in hamsters, mice, and guinea pigs were also examined.PFDA caused a severe reduction in body weight in all four speciesstudied. A reduction in food intake was observed in rats andhamsters. However, hamsters continued to consume food at a reducedlevel, while rats stopped eating for a 5 to 6-day period about6 days after dosing. The PFDA-induced pathological changes inthe hamsters, mice, and guinea pigs resembled those seen inrats to varying degrees. As in the rat, PFDA caused a markedliver enlargement in mice and hamsters and a moderate swellingin guinea pigs. This hepatomegaly was ascribed primarily toindividual cell swelling. Thymic atrophy was noted in PFDA-treatedhamsters, mice, and guinea pigs. Seminiferous tubular degenerationobserved in hamsters and guinea pigs, but not in mice, was notas severe as in the rat, where in some cases frank necrosishas been seen. Ultrastructural changes in the livers of allPFDA-treated animals, regardless of species, included disruptionof the rough endo plasmic reticulum, rounding and swelling ofthe mitochondria with related structural alter ations, and mildto extensive proliferation of peroxisomes. This peroxisome proliferativeresponse was greatest in mice and almost absent in guinea pigs.Accumulation of lipid droplets in liver cells due to PFDA treatmentwas more pronounced in hamsters and guinea pigs than in ratsand mice. PFDA-induced hepatomegaly with a concomitant increasein peroxisomes in several rodent species may be associated withan impairment of normal lipid metabolism in the liver by PFDA.