1 December 2023

IARC Monographs evaluate the carcinogenicity ofperfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS)
Questions and Answers (Q&A)
The meeting for IARC Monographs Volume 135: Perfluorooctanoic acid (PFOA) and Perfluorooctanesulfonicacid (PFOS), convened by the International Agency for Research on Cancer (IARC) in Lyon, France, took
place on 7–14 November 2023.
The Working Group of 30 international experts from 11 countries evaluated the carcinogenicity ofperfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS).
Moreinformationabout

themeetingisavailableontheIARCMonographs

website:https://monographs.iarc.who.int/iarc-monographs-volume-135/.
The outcome of the assessment has been published in a summary article in The Lancet Oncology 1 and will be
described in detail in Volume 135 of the IARC Monographs, to be published in 2024.
1. What are PFOA and PFOS?
Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) have been the most widely usedchemicals in a large group of fluorinated compounds called per- and polyfluoroalkyl substances (PFAS).
PFOA and PFOS have been used in a wide range of applications, such as fluoropolymer production; aerosolpropellants; solvents; pesticides; antifoaming agents; surface treatments for household products, textiles,leather, masonry, and paper and board, including food packaging; levelling agents in paints, coatings, andwaxes; plastics; lubricants and greases; and firefighting foams. Depending on the country, the use of PFOAand PFOS has decreased or been completely phased out in the past decades because of agreements andregulations such as the Stockholm Convention. However, exposure continues via products made before theregulations came into effect and via the environment, because of the extreme persistence of these chemicals.
They can also be formed by precursors, which are other PFAS chemicals that can transform into PFOA andPFOS; thus, even if direct production of PFOA and PFOS ceases, they may still occur in the environment.

(2023). 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
1 Zahm S, Bonde JP, Chiu WA, Hoppin J, Kanno J, Abdallah M, et al.

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2. What are the results of the evaluation?
The results of the evaluation are summarized in Table 1.
Table 1. Summary of classifications in IARC Monographs Volume 135
Agent

Evidence stream
Cancer inCancer in

Mechanistic evidence

humansexperimental(key characteristics ofanimals

carcinogens)

Sufficient

Strong in exposed humans

Perfluorooctanoic acid

Limited (renal(PFOA)

cell carcinoma(KCs 4, 7), human primary

and testicular

cells (KCs 5, 7, 8),cancer)

experimental systems (KCsOverallevaluationGroup 14, 5, 7, 8, 10)
Perfluorooctanesulfonic

Inadequate

LimitedStrong in exposed humans

acid(KCs 4, 7), human primary(PFOS)

cells (KCs 5, 7, 8),Group 2B

experimental systems (KCs4, 5, 7, 8, 10)KCs, key characteristics of carcinogens; KC4, induces epigenetic alterations; KC5, induces oxidative stress; KC7, isimmunosuppressive; KC8, modulates receptor-mediated effects; KC10, alters cell proliferation, cell death, or nutrient
supply.

3. How did the Working Group arrive at these classifications?
PFOA is carcinogenic to humans (Group 1). The Group 1 evaluation for PFOA was based on the combinationof sufficient evidence for cancer in experimental animals and strong mechanistic evidence (for epigeneticalterations and immunosuppression) in exposed humans. In addition, there was limited evidence for cancer inhumans (for renal cell carcinoma and testicular cancer).
PFOS is possibly carcinogenic to humans (Group 2B). The Group 2B evaluation for PFOS was based onstrong mechanistic evidence across test systems, including in exposed humans.
4. Have these agents previously been evaluated by the IARC Monographs programme?
PFOA was previously evaluated in 2014 and was classified in Group 2B (with limited evidence for cancer inhumans). PFOS was evaluated for the first time.

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5. Why was PFOA re-evaluated?
The Advisory Group to Recommend Priorities for the IARC Monographs during 2020–2024 2 recommended
that PFOA should be re-evaluated with high priority by the IARC Monographs programme. This
recommendation was based on the publication of new evidence coming from several studies on cancer inhumans, an anticipated animal bioassay, and a large volume of scientific literature on mechanistic data.

6. Was there key new evidence that was used in the re-evaluation of PFOA?
Since the previous evaluation of PFOA, the interest in and scientific research on these compounds have
surged. The number of animal bioassays has approximately doubled since the previous evaluation, and there
has been a vast increase in the number of mechanistic studies, including studies in exposed humans. There
has also been a large increase in the number of studies on cancer in humans, mainly in the general
population with relatively low exposure to PFOA and PFOS. Exceptionally, the Working Group itself
conducted an ecological analysis of rates of orchiectomy, an indicator of testicular cancer, in relation toaverage serum levels of PFOA by municipality in the Veneto Region of Italy. 3,4

7. Where can these chemicals be found?
Because of their chemical stability, PFOA and PFOS are ubiquitously present in the environment, even inremote locations. Increased concentrations have been measured at some contaminated sites because ofindustrial emissions and use in firefighting foams.
PFOA and PFOS have been found in food packaging, carpets, building materials, cosmetics, cookware,waterproof clothing, and firefighting foams. However, in most countries the use of PFOA and PFOS in theseproducts was phased out in the past two decades, and exposure may occur due to legacy contamination. Incountries where the use of PFOA and PFOS has not been phased out, there may be continuing exposure tothese agents via consumer products.
In industry, PFOA and PFOS have been used for their surface-tension-lowering and stain-repellent properties,
for example in plastic manufacturing or metal plating.

2 IARC (2019). Report of the Advisory Group to Recommend Priorities for the IARC Monographs during 2020–2024. Lyon,France: International Agency for Research on Cancer. Available from: https://monographs.iarc.who.int/wpcontent/uploads/2019/10/IARCMonographs-AGReport-Priorities_2020-2024.pdf.
3Sistema Epidemiologico Regionale (2016). Ricognizione epidemiologica iniziale sulle orchiectomie per tumore deltesticolo rilevate nell’area interessata dalla contaminazione idropotabile da PFAS. Padova, Italy: Sistema EpidemiologicoRegionale. Available from: https://sian.aulss9.veneto.it/index.cfm?method=mys.apridoc&iddoc=809 [Italian]
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Pitter G, Da Re F, Canova C, Barbieri G, Zare Jeddi M, Daprà F, et al. (2020). Serum levels of perfluoroalkyl substances(PFAS) in adolescents and young adults exposed to contaminated drinking water in the Veneto Region, Italy: a crosssectional study based on a health surveillance program. Environ Health Perspect. 128(2):27007.
https://doi.org/10.1289/EHP5337

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The use of these chemicals in fluoropolymer production and in firefighting foams has led to environmental
contamination from industrial emissions and run-off from firefighter training activities. In addition, PFOA andPFOS may enter the environment via industrial and municipal waste disposal.

8. Who is exposed to these agents, and how?
Exposures are expected to be highest among workers involved in producing PFOA or PFOS or using thesechemicals 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 came intoeffect, occupational exposure is likely to have decreased in some countries, although it is likely to becontinuing in other countries. 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 asaqueous 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.

9. On the basis of this evaluation, what recommendations does IARC make?
IARC is a research organization that generates and evaluates evidence related to the causes of cancer but
does not make health recommendations. However, the evaluations made by the IARC Monographs
programme are often used as a basis for national and international policies, guidelines, and recommendations
to minimize cancer risks.
You can find more information on the IARC Monographs evaluation process here:
https://monographs.iarc.who.int/wp-content/uploads/2018/07/QA_ENG.pdf.

10. What does the IARC Monographs classification mean in terms of risk?
The IARC Monographs classification indicates the strength of the evidence that a substance or agent cancause cancer. The IARC Monographs programme seeks to identify cancer hazards, meaning the potential forthe exposure to cause cancer. However, the classification does not indicate the level of cancer risk associatedwith exposure at different levels or in different scenarios. The cancer risk associated with substances oragents that are assigned the same classification may be very different, depending on factors such as the typeand extent of exposure and the size of the effect of the agent at a given exposure level.

411. What are the different strength-of-evidence evaluation groups used by the IARC Monographs?
The strength-of-evidence groups that contribute to each evaluation are summarized in Table 2.
Table 2. Strength-of-evidence groups used by the IARC Monographs

12. What are the four different categories into which agents are classified by the IARC Monographs?
Group 1: The agent is carcinogenic to humans.
This category is used when there is sufficient evidence for cancer in humans. In other words, there isconvincing evidence that the agent causes cancer in humans. The evaluation is usually based on the resultsof epidemiological studies showing development of cancer in exposed humans. Agents can also be classified
in Group 1 on the basis of sufficient evidence for cancer in experimental animals supported by strong
evidence in exposed humans that the agent has mechanistic effects that are important for cancer
development. This was the basis of the Group 1 evaluation for PFOA.
Group 2:This category includes agents with a range of evidence regarding cancer in humans and in experimental
animals. At one extreme of the range are agents with positive but not conclusive evidence regarding cancer inhumans. At the other extreme are agents for which evidence in humans is not available but for which there is5sufficient evidence for cancer in experimental animals. There are two subcategories, which indicate different
levels of evidence.
Group 2A: The agent is probably carcinogenic to humans.
This category is used in four different scenarios:
1. When there is limited evidence for cancer in humans and sufficient evidence for cancer inexperimental animals (“limited evidence for cancer in humans” means that a positive association has
been observed between exposure to the agent and cancer but that other explanations for theobservations, technically termed “chance”, “bias”, or “confounding”, could not be ruled out withreasonable confidence);
2. When there is limited evidence for cancer in humans and strong mechanistic evidence;
3. When there is sufficient evidence for cancer in experimental animals and strong mechanistic evidence
in human primary cells or tissues;
4. When, based on mechanistic considerations, the agent belongs to a class of agents of which one ormore is probably carcinogenic to humans (Group 2A) or carcinogenic to humans (Group 1).
These scenarios may also occur simultaneously within a Group 2A classification.
Group 2B: The agent is possibly carcinogenic to humans.
This category is used when there is limited evidence for cancer in humans and less-than-sufficient evidence
for cancer in experimental animals. It may also be used when the evidence regarding cancer in humans does
not permit a conclusion to be drawn (referred to as inadequate evidence) but there is sufficient evidence forcancer in experimental animals. It can also be used when there is strong mechanistic evidence, as was thecase for PFOS.
Group 3: The agent is not classifiable as to its carcinogenicity to humans.
This category is used most commonly when the evidence is inadequate regarding cancer in humans andinadequate or limited for cancer in experimental animals, and mechanistic evidence is less than strong.
Limited evidence for cancer in experimental animals means that the available information suggests a
carcinogenic effect but is not conclusive.

13. How was the evidence reviewed in the IARC Monographs evaluation?
During an IARC Monographs evaluation, experts critically review the scientific evidence according to strict
criteria, which focus on determining the strength of the available evidence that the agent causes cancer.
These criteria are described in the Preamble to the IARC Monographs, which is available on the IARC
Monographs website: https://monographs.iarc.who.int/wp-content/uploads/2019/07/Preamble-2019.pdf.
The experts critically review four types of data:•

the situations in which people are exposed to the agent;6•

epidemiological studies on cancer in humans exposed to the agent (scientific evidence regarding
cancer in humans);•

experimental studies of cancer in laboratory animals treated with the agent (scientific evidence
regarding cancer in experimental animals); and•studies on how cancer develops in response to the agent (scientific evidence on carcinogenmechanisms).

For more information, please contact:
Véronique Terrasse, Communications Team, at +33 (0)6 45 28 49 52 or terrassev@iarc.who.int
or IARC Communications, at com@iarc.who.int
The International Agency for Research on Cancer (IARC) is part of the World Health Organization. Its mission
is to coordinate and conduct research on the causes of human cancer, the mechanisms of carcinogenesis,
and to develop scientific strategies for cancer control. The Agency is involved in both epidemiological andlaboratory research and disseminates scientific information through publications, meetings, courses, andfellowships. If you wish your name to be removed from our press release emailing list, please write tocom@iarc.who.int.

Research reported in this publication was supported by the National Cancer Institute of the National Institutesof Health under Award Number R01CA022193. The content is solely the responsibility of the authors anddoes not necessarily represent the official views of the National Institutes of Health.

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