<em>IARC Monographs</em> evaluate the carcinogenicity of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) (2024)

1 December 2023

Dietary exposures Environmental exposures Kidney cancer Occupational exposures Testicular cancer

The International Agency for Research on Cancer (IARC), the cancer agency of the World Health Organization (WHO), has evaluated the carcinogenicity of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS).

PFOA and PFOS are widely used chemicals in a large group of fluorinated compounds called per- and polyfluoroalkyl substances (PFAS), sometimes called “forever chemicals” because they do not degrade easily.

A Working Group of 30 international experts from 11 countries was convened by the IARC Monographs programme for a meeting on 7–14 November 2023 in Lyon.

After thoroughly reviewing the extensive published literature, the Working Group classified PFOA as carcinogenic to humans (Group 1) and PFOS as possibly carcinogenic to humans (Group 2B).

A summary of the final evaluations has now been published online in The Lancet Oncology. The detailed assessment will be published in 2024 as Volume 135 of the IARC Monographs.

Results of the evaluation
The Working Group conducted a cancer hazard evaluation of PFOA and PFOS.

PFOA is carcinogenic to humans (Group 1), on the basis of sufficient evidence for cancer in experimental animals and strong mechanistic evidence (for epigenetic alterations and immunosuppression) in exposed humans. There was also limited evidence for cancer in humans (renal cell carcinoma and testicular cancer) and strong mechanistic evidence in human primary cells and experimental systems (for epigenetic alterations and immunosuppression, as well as several other key characteristics of carcinogens).

PFOS is possibly carcinogenic to humans (Group 2B), on the basis of strong mechanistic evidence across test systems, including in exposed humans (for epigenetic alterations and immunosuppression, as well as several other key characteristics of carcinogens). There was also limited evidence for cancer in experimental animals and inadequate evidence regarding cancer in humans.

Exposure to PFOA and PFOS
PFOA and PFOS are ubiquitously present in the environment, even in the most remote areas. They have also been specifically found in a wide range of products, such as food packaging, carpets, building materials, cosmetics, cookware, waterproof clothing, and firefighting foams, and they have many other industrial applications. PFOA and PFOS have also been found in drinking-water supplies, especially near sites where they are produced or used extensively.

Exposures are expected to be highest among workers involved in producing PFOA or PFOS or using these chemicals directly in the manufacture of other products. Inhalation is thought to be the main route of exposure for workers, although dermal exposure is possible. Since restrictions on the use of these agents in some countries came into effect, occupational exposure is likely to have decreased, although it is likely to be continuing in countries that have not introduced restrictions. There is continuing exposure in waste management.

PFOA and, to a much larger extent, PFOS have been widely used in some firefighting foams (also known as aqueous film-forming foams, AFFFs), which are used particularly in airport and military firefighting operations as well as in training. The use of PFOA and PFOS in these applications has been banned in many countries, but exposure of firefighters to PFOA and PFOS is possible when old stocks of AFFFs are used.

The general population is exposed mainly via food and drinking-water, and potentially via consumer products. At contaminated sites, drinking-water is the main exposure source for the general population.

IARC Monographs classification
The IARC Monographs classification indicates the strength of the evidence that a substance or agent can cause cancer. The IARC Monographs programme seeks to identify cancer hazards, meaning the potential for the agent to cause cancer. For example, Group 1 is the highest strength-of-evidence category, indicating that an agent can cause cancer. However, the classification does not indicate the level of cancer risk associated with exposure at different levels or in different scenarios. The cancer risk associated with substances or agents that are assigned the same classification may be very different, depending on factors such as the type and extent of exposure and the size of the effect of the agent at a given exposure level.

Zahm S, Bonde JP, Chiu WA, Hoppin J, Kanno J, Abdallah M, et al.
Carcinogenicity of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS).
Lancet Oncol, Published online 30 November 2023;
https://doi.org/10.1016/S1470-2045(23)00622-8