5.1. Exposure data

Perfluorooctanoic acid (PFOA) is a synthetic fluorinated carboxylic acid. There are two production methods: the electrochemical fluorination process results in a mixture of branched and straight-chain isomers of the ammonium salt, while the telomerization process, a method in use since the early 2000s, results in an isomerically pure, straight-chain product. PFOA and its salts have been mainly used as emulsifiers in the production of fluoropolymers such as polytetrafluoroethylene. PFOA has been used in metal cleaners, electrolytic-plating baths, self-shine floor polishes, cement, fire-fighting formulations, varnishes, emulsion polymerization, lubricants, gasoline, leather, and textile treatments and as non-stick coatings on cookware and in paper coatings such as food packaging. PFOA is persistent in the environment and has been detected in air, water, dust, and food. For most of the general population, the predominant sources of exposure are food (including transfer of PFOA from food packaging) and dust. Serum concentrations of perfluorooctanoate of less than about 10 µg/L have been measured in the general population worldwide; serum concentrations increased over time until about 2000, and have since remained constant or decreased. In people living near industrial sources of perfluorooctanoate, mean serum concentrations have ranged from near-background concentrations to > 200 µg/L. In these groups, the predominant route of exposure was drinking-water. Occupational exposure, through inhalation and dermal contact, occurs during fluoropolymer production using PFOA, and mean serum concentrations in groups of workers with the highest exposure were measured as > 1000 µg/L.

5.2. Human carcinogenicity data

The literature on the epidemiology of cancer in relation to PFOA is relatively small and includes studies in three different types of populations: workers exposed in chemical plants producing or using PFOA, high-exposure communities (i.e. areas surrounding a plant with documented release of PFOA and contamination of public and private water supplies), and studies in the general population with background exposures.

5.3. Animal carcinogenicity data

PFOA was administered in the feed in one study of carcinogenicity in male and female rats, and in another study in male rats. PFOA increased the incidence of testicular Leydig cell adenoma in males in both studies, and increased the incidences of hepatocellular adenoma and pancreatic acinar cell adenoma in the study in male rats only.

PFOA was also shown to promote hepatocarcinogenesis in two feeding studies in male rats and two feeding studies in rainbow trout.

5.4. Mechanistic and other relevant data

PFOA does not undergo metabolism in the experimental systems studied or in humans. It is readily absorbed via all routes of exposure and is excreted into the urine. Among the species studied, humans are unique in that the reabsorption of PFOA in the kidneys is highly efficient, leading to much longer retention in the body when compared with all other animals. Therefore, the body burden of PFOA experienced by humans is much greater than in experimental animals.

PFOA is not DNA-reactive, and gives negative results in an overwhelming number of assays for direct genotoxicity. Therefore, there is strong evidence that direct genotoxicity is not a mechanism of PFOA carcinogenesis. Some studies with PFOA indicate that indirect DNA damage may result from induction of oxidative stress, therefore there is moderate evidence that genotoxicity overall is not a mechanism of PFOA carcinogenesis.

Several studies in humans have examined the relationship between exposure to PFOA and toxicity, and suggest that PFOA may cause liver injury. In experimental animals, the liver is a well-established target for toxicity. Potential mechanisms for PFOA-induced toxicity and carcinogenicity in the liver include PPARα activation, involvement of other molecular pathways (i.e. constitutive androstane receptor, pregnane X receptor, estrogen receptor), and cytotoxicity. There is moderate evidence for these mechanisms, largely from studies in rats and mice. Based on the available evidence, human relevance of the liver findings in rodents cannot be excluded.

The effects of PFOA in other organs are not so well established, but modulation of inflammatory pathways and hormone levels has been reported. Studies in human cells, rodents, and fish, have documented perturbation of molecular pathways involving reproductive hormones and hormone receptors, such as activation of estrogen receptor, interference with testosterone/estradiol balance, and induction of aromatase, and effects on reproductive organs consistent with estrogenicity. Although there is moderate evidence that PFOA affects reproductive-hormone pathways, there is weak evidence for their relevance to PFOA-associated carcinogenesis.

Overall, there is moderate evidence for mechanisms of PFOA-associated carcinogenesis, including some evidence for these mechanisms being operative in humans.