On their introduction in the 1940s, PFASs were considered inert. Early occupational studies revealed elevated levels of fluorochemicals, including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA, C8), in the blood of exposed industrial workers, but cited no ill health effects. These results were consistent with the measured serum concentrations of PFOS and PFOA in 3M plant workers ranging from 0.04 to 10.06 ppm and 0.01 to 12.70 ppm, respectively, well below toxic and carcinogenic levels cited in animal studies. Given, however, the "forever chemical" property of PFASs (serum elimination half-life of 4–5 years) and widespread environmental contamination, molecules have been shown to accumulate in humans to such a degree that adverse health outcomes have resulted.
Hormone-disrupting chemicals, including PFASs, are linked with rapid declines in human fertility. In a meta-analysis for associations between PFASs and human clinical biomarkers for liver injury, authors considered both PFAS effects on liver biomarkers and histological data from rodent experimental studies and concluded that evidence exists showing that PFOA, perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) are hepatotoxic to humans.
Many comprehensive epidemiological studies linking adverse human health effects to PFASs, particularly PFOA, come from the C8 Science Panel. The panel was formed as part of a contingency to a class action lawsuit brought by communities in the Ohio River Valley against DuPont in response to landfill and wastewater dumping of PFAS-laden material from DuPonts West Virginia Washington Works Plant. The panel measured PFOA (also known as C8) serum concentrations in 69,000 individuals from around DuPonts Washington Works Plant and found a mean concentration of 83.0 ng/mL, compared to 4 ng/mL in a standard population of Americans. This panel reported probable links between elevated PFOA blood concentration and hypercholesterolemia, ulcerative colitis, thyroid disease, testicular cancer, kidney cancer as well as pregnancy-induced hypertension and preeclampsia.