The Toxicology of Perfluorooctanoate

Abstract

PFOA is a peroxisome proliferator (PPAR agonist) and exerts morphological and biochemical effects characteristic of PPAR agonists. These effects include increased beta-oxidation of fatty acids, increases in several cytochrome P-450 (CYP450)-mediated reactions, and inhibition of the secretion of very low-density lipoproteins and cholesterol from the liver. These effects on lipid metabolism and transport result in a reduction of cholesterol and triglycerides in serum and an accumulation of lipids in the liver. The triad of tumors observed (liver, Leydig cell, and pancreatic acinar-cell) is typical of many PPAR agonists and is believed to involve nongenotoxic mechanisms. The hepatocellular tumors observed in rats are likely to have been the result of the activation of the peroxisome proliferator activated receptor alpha (PPARalpha). The tumors observed in the testis (Leydig-cell) have been hypothesized to be associated with an increased level of serum estradiol in concert with testicular growth factors. The mechanism responsible for the acinar-cell tumors of the pancreas in rats remains the subject of active investigation. The mechanism resulting in the hepatocellular tumors in rats (PPARalpha activation) is not likely to be relevant to humans. Similarly, the proposed mechanism for Leydig-cell tumor formation is of questionable relevance to humans. Acinar tumors of the pancreas are rare in humans, and the relevance of the these tumors, as found in rats, to humans is uncertain. Epidemiological investigations and medical surveillance of occupationally exposed workers have not found consistent associations between PFOA exposure and adverse health effects.

Evaluation of dicationic reagents for their use in detection of anions using positive ion mode ESI-MS via gas phase ion association

“…Perfluoro-octanoic acid (PFOA), a large, anionic fluorocarbon, is unlike any of the other anions. This, along with recent research interest in this compound as an environmental contaminant, makes it a good choice for inclusion in this study [25,26].…”

In utero exposure to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) did not increase body weight or intestinal tumorigenesis in multiple intestinal neoplasia (Min/+) mice

“…In addition to their hormonal effects, animal studies have demonstrated developmental toxicity, reproductive toxicity, hepatotoxicity, neurotoxicity, immunotoxicity and tumorigenicity of the perfluorinated compounds (Johansson et al, 2008;Kennedy et al, 2004;Lau et al, 2004). Hepatocellular adenomas, testicular Leydig cell adenomas and pancreatic acinar cell adenomas have been reported in rats after exposure to PFOA in the diet for 2 years (Biegel et al, 2001;Butenhoff et al, 2012b).…”

Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers

“…In one of the aforementioned analyses, Olsen et al (2003a) reported a positive association between PFOA and serum cholesterol and triglycerides among participants of a fluorochemical medical surveillance program conducted in 2000 at the 3M Antwerp and Decatur facilities. They considered this a spurious finding given the toxicological evidence in mice and rats that shows PFOA, a peroxisome proliferator alpha receptor agonist (PPARa), exerts effects including increased beta-oxidation of fatty acids, inhibition of the secretion of very low-density lipoproteins and cholesterol from the liver, and a reduction of cholesterol and triglycerides in serum and accumulation of lipids in the liver (Maloney and Waxman 1999;Xie et al 2003;Kennedy et al 2004). No associations were reported between PFOA and either serum cholesterol or triglycerides for the Cottage Grove male employees who participated in the same fluorochemical medical surveillance program in 2000 (Olsen et al 2003c).…”