US EPA

3858674 

Journal Article 

Dose-response hapatotoxicity of the peroxisome proliferator, perfluorodecanoic acid and the relationship to phospholipid metabolism in rats 

Adinehzadeh, M; Reo, NV; Jarnot, BM; Taylor, CA; Mattie, DR 

1999 

1 

Toxicology
ISSN: 0300-483X
EISSN: 1879-3185 

134 

2-3 

179-195 

English 

10403636 

10.1016/S0300-483X(99)00038-4 

WOS:000081213600008 

https://search.proquest.com/docview/17304939?accountid=171501
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Perfluorodecanoic acid (PFDA) is a potent peroxisome proliferator that causes hepatotoxicity but lacks tumor-promoting activity in rats. We previously showed that a single dose of PFDA at 50 mg/kg (approximately LD50) causes an elevation in liver phosphocholine (PCho) and other effects related to phospholipid metabolism. In this study, we examined metabolic effects in the dose range 2-50 mg/kg in rats. At doses < or =20 mg/kg, PFDA is significantly less hepatotoxic than the LD50 as manifested by electron microscopy and measurements of daily food consumption and body weight. At 50 mg/kg rat serum tumor necrosis factor (TNF)-alpha concentration was increased 8-fold, while at 15 mg/kg there was no apparent increase in this cytokine. This lower dose, however, induces metabolic effects similar to those seen at the LD50. Liver fatty acyl-CoA oxidase activity showed a dose-dependent increase from 5-25 mg/kg PFDA. Treatments at 15 and 50 mg/kg caused a significant increase in liver phosphatidylcholine (28 and 66%) and phosphatidylethanolamine (31 and 74%). Both doses caused a significant increase in liver PCho but did not affect liver ATP levels, as manifested in 31P nuclear magnetic resonance (NMR) spectra from rat livers in vivo. These data suggest that the increase in liver [PCho] observed following PFDA exposure in rats represents a specific metabolic response, rather than a broad-range hepatotoxic effect. 

perfluorodecanoic acid; peroxisome proliferator; hepatotoxicity