The biochemical toxicity of perfluorodecanoic acid in the mouse is different from that of 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Perfluorodecanoic acid (PFDA) is an industrial surfactant that has been reported to produce signs of toxicity in rats similar to those due to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to characterize the biochemical toxicity of PFDA in the mouse and to determine whether PFDA toxicity is mediated by the Ah locus, congenic female C57BL/6J mice differing only at the Ah locus (normal homozygous responsive Ahb/b, heterozygous responsive Ahb/d, and homozygous nonresponsive Ahd/d) were administered a single oral dose of PFDA. The wild type (Ahb/b) mice were killed 2, 7, 14, or 30 days after administration of 0, 40, 80, 100, 120, or 160 mg PFDA/kg. Mice from the other two congenic strains were killed 30 days after dosing with 0, 40, 80, or 160 mg/kg. PFDA produced a 2.5-fold increase in absolute liver weight, a 5- to 15-fold increase in hepatic fatty acyl Co-A oxidase activity, and a 70% decrease in hepatic ethoxyresorufin O-deethylase (EROD) activity. These effects were dose and time dependent. Total hepatic lipids were increased at an early time point and at the lowest dose. At later time periods and/or higher doses, the lipid concentration was decreased approximately 20% from that of controls. Hepatic protein concentrations were depressed approximately 25% from control levels 30 days after treatment. There was little difference in any of these parameters between responsive (Ahb/b, Ahb/d) and nonresponsive (Ahd/d) mice. These results suggest that the Ah allele has little effect in regulating the toxicity of PFDA in the mouse and that the biochemical response to PFDA in the mouse is markedly different from that of TCDD. Furthermore, the biochemical response to PFDA in the mouse is different from that reported in the rat.
Brewster
D W
DW
Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Birnbaum
L S
LS
D042962:Acyl-CoA Oxidase; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D003652:Decanoic Acids / Q000633:toxicity*; D004147:Dioxins / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D008055:Lipids / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000032:analysis; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011506:Proteins / Q000032:analysis; D013045:Species Specificity
D003652:Decanoic Acids; D004147:Dioxins; D005466:Fluorocarbons; D008055:Lipids; D000072317:Polychlorinated Dibenzodioxins; D011506:Proteins; C036567:perfluorodecanoic acid; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; D042962:Acyl-CoA Oxidase