As early as the 1980s PFOS and related compounds were found to be persistent and bioaccumulative and they were suspected to have toxic and / or carcinogenic properties in cases of long-term exposure.In higher organisms PFOS is mainly found in blood, kidneys and the liver.Both substances have long half-lives (residence times) in the human body of respectively 5,4 and 4 years for PFOS and PFOA.General population surveys have shown that the average concentration of PFOS in the blood is 20.7 µg/L and of PFOA 3.9 µg/L.In a study group exposed to contaminated drinking water with PFOA the average concentration was 354 µg/L and employees of a PFAS manufacturer showed blood concentrations of 1,320 µg/L of PFOS and 1.760 µg/L to PFOA.

Exposure to PFOS or PFOA occurs mainly through food, contaminated drinking water, breathing polluted (indoor) air or contact with treated materials such as packaging for food or impregnated clothing.Both substances are accumulated in fish, but PFOS to a greater extent than PFOA.

The United States population has shown a declining trend of concentrations of PFOS and PFOA. This is attributed to the change in production and a strong decrease of PFOA and PFOS applications in the last few years. However, there is an upward trend for PFNA (the sister of PFOA with 9 C-atoms), but these concentrations are lower than the concentrations of PFOS and PFOA in the human body.

In the toxicology of PFAS we see the phenomenon that in test animals a gender-dependent residence time in the body (half-life) is related to hormonally regulated secretion.The gender-dependent residence time is not uniform though, but depends on the substance and the animal species.The large differences in residence time between different species are also striking.

MECHANISM

Some biological targets of PFOS and PFOA are similar.PFOS and PFOA accumulate in the liver, and both have the ability to activate the PPAR-α (peroxisome proliferator-activated receptor-α). Activation of the receptor in rodents leads to a series of biochemical events (mainly, but not exclusively in the liver), for example, the increased production of hydrogen peroxide (H2O2), which may result in oxidative stress by its generation of free hydroxyl radicals.These in their turn may lead to increased DNA damage or inhibition of intercellular communication.However, activation of PPAR-α also effects changes in the lipid metabolism.In addition, it has been shown that PFOS and PFOA induce several metabolizing enzymes, may induce apoptosis (the process by which a cell destroys itself from within) and interfere with hormone levels.

PFOS and PFOA are acutely toxic only at relatively high concentrations (in the order of milligrams).After chronic exposure to low concentrations, effects of PFOS and PFOA in the liver were reported.Enlargement of the liver and disturbance of liver function are consistently observed in different animals.It also appears that PFOS and PFOA may affect the reproduction in particular, while the exposure in the womb is critical for mortality, growth retardation or slower skeletal development in puppies.The causes of these effects on the offspring are unknown; possibly changes in thyroid hormone metabolism are involved here.Recent studies in mice also showed that immunotoxic effects of PFOS and PFOA may be expected at environmentally relevant concentrations. In general PFOS and PFOA were not found to induce mutagenicity and limited carcinogenicity limited.

Since 1976 potential health effects of PFOA and PFOS by occupational exposure of workers are being monitored by 3M, the major producer of these substances.To date, no significant associations between occupational exposure to PFOA and overall or cause-specific mortality statistics have been proved.For PFOS on the other hand, there are indications that occupational exposure results in abnormal liver function parameters and that it produces a significantly higher incidence of cancer.Especially cancers of the reproductive organs were more common in male workers with the highest and most prolonged occupational exposure.PFOS and PFOA can be transmitted through the placenta from mother to foetus.The concentration of PFOS in umbilical cord blood was 1.25 to 2.5 times lower than in maternal plasma.For PFOA there is no difference between cord blood and maternal plasma. PFOA can cross theplacenta from mother to fetes.Also recent epidemiological studies showed a significant negative correlation between the presence of PFOS or PFOA in cord blood and birth weight.

Based on toxicity data, the CONTAM Panel of the European Food Safety Agency (EFSA) for human exposure to PFOS and PFOA has calculated a maximum tolerable daily intake (Tolerable Daily Intake, TDI) of 150 ng / kg per day, respectively 1.5 µg / kg per day.In addition, the EFSA notes that health effects to the public are not very likely, but that monitoring over time is certainly recommended.