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-chain fatty acid. Its toxicity in rats has been reported to resemble that produced by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice which are "responsive" to TCDD toxicity carry the Ahb allele, while mice homozygous for the Ahd gene are less sensitive to TCDD toxicity. To characterize the toxicity of PFDA and determine if it is under the control of the Ah locus, female responsive C57BL/6N (Ahb/b) mice and congenic C57BL/6J mice, differing only at the Ah locus (responsive, Ahb/b; heterozygous responsive, Ahb/d and "nonresponsive," Ahd/d), were administered a single oral dose of PFDA, at levels from 0 to 320 mg/kg body weight, observed daily for overt signs of toxicity, and weighed three times weekly. In the wild-type congenic C57BL/6J (Ahb/b) subline, mice were killed at 2, 7, 14, and 30 days following exposure. All other mice were killed on Day 30. Serum was taken from the C57BL/6N mice for analysis of thyroid hormone levels. Selected organs from all mice were weighed and fixed for histopathological examination. Dose-related mortality was observed as early as 5 days postexposure and time-to-death was inversely related to dose. Dramatic decreases in body weight occurred shortly following treatment in all strains. Serum triiodothyronine (T3) and thyroxine (T4) levels increased with increasing dose. There was a marked increase (p less than 0.05) in absolute and relative liver weights and a significant decrease in thymus weights. Hepatocellular hypertrophy was observed in all treated mice other than controls. A marked increase in hepatocyte peroxisomes was observed in all treatment groups. Thus, in contrast to TCDD, the acute toxicity of PFDA in the female C57BL/6 mouse does not vary with the Ah allele and is distinct from that reported for TCDD.
Harris
M W
MW
Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Uraih
L C
LC
Birnbaum
L S
LS
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D003652:Decanoic Acids / Q000633:toxicity*; D004147:Dioxins / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D008099:Liver / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013045:Species Specificity; D013963:Thyroid Hormones / Q000097:blood
D003652:Decanoic Acids; D004147:Dioxins; D005466:Fluorocarbons; D000072317:Polychlorinated Dibenzodioxins; D013963:Thyroid Hormones; C036567:perfluorodecanoic acid