Acute Toxicity of Perfluorodecanoic Acid in C57BL/6 Mice Differs from 2,3,7,8-Tetrachlorodibenzo-p-dioxin

Perfluorodecanoic acid (PFDA) is a 10-carbon straight-chainfatty acid. Its toxicity in rats has been reported to resemblethat produced by exposure to 2,3,7,8-tetrachlorodibenzo-P-dioxin(TCDD). Mice which are "responsive" to TCDD toxicity carry theAh^b allele, while mice homozygous for the Ah^d gene are lesssensitive to TCDD toxicity. To characterize the toxicity ofPFDA and determine if it is under the control of the Ah locus,female responsive C57BL/6N (Ah^b/d) mice and congenic C57BL/6Jmice, differing only at the Ah locus (responsive, Ah^b/b; heterozygousresponsive, Ah^b/d and "nonresponsive," Ah^d/d), were administereda single oral dose of PFDA, at levels from 0 to 320 mg/kg bodyweight, observed daily for overt signs of toxicity, and weighedthree times weekly. In the wild-type congenic C57BL/6J (Ah^b/b)subline, mice were killed at 2, 7, 14, and 30 days followingexposure. All other mice were killed on Day 30. Serum was takenfrom the C57BL/6N mice for analysis of thyroid hormone levels.Selected organs from all mice were weighed and fixed for histopathologicalexamination. Dose-related mortality was observed as early as5 days postexposure and time-to-death was inversely relatedto dose. Dramatic decreases in body weight occurred shortlyfollowing treatment in all strains. Serum triiodothyronine (T₃)and thyroxine (T₄) levels increased with increasing dose. Therewas a marked increase (p < 0.05) in absolute and relativeliver weights and a significant decrease in thymus weights.Hepatocellular hypertrophy was observed in all treated miceother than controls. A marked increase in hepatocyte peroxisomeswas observed in all treatment groups. Thus, in contrast to TCDD,the acute toxicity of PFDA in the female C57BL/6 mouse doesnot vary with the Ah allele and is distinct from that reportedfor TCDD.