Reflections on Formaldehyde Carcinogenicity

Formaldehyde carcinogenicity is now a commonly accepted notion in society, as well as in anatomic pathology laboratories. Guilty on arrival. However, the background of this concept is far beyond a reasonable doubt.

There is not now even an echo politically charged dispute of 1980s between U.S. Environment Protection Agency (EPA), Occupational Safety & Health Agency (OSHA), College of American Pathologists (CAP), Formaldehyde Institute, DuPont, and labor unions on the evaluation of formaldehyde occupational exposure risk, which was based on the assessment of formaldehyde as “probable carcinogen” at that time. 1 In 1989, the American Medical Association (AMA) summarized the literature data through 1985 on occupational exposure to formaldehyde. Mentioning that regulatory agencies as OSHA, regarded formaldehyde as a possible human carcinogen, AMA observed that “this is a controversial opinion in the view of many industry and academic scientists.”1

Times have changed. The main organization influencing the assessment of reagents as carcinogenic is the World Health Organization’s (WHO) International Agency for Research on Cancer (IARC) based in Lyon, France. IARC summarizes literature data predominantly epidemiological research, as well as some experimental studies. According to IARC Press Release No 153, 15 June 2004 formaldehyde is placed in Group I – known carcinogens- along with such substances as asbestos and benzene.2 The dispute is over.

However, the Monograph Programme, the IARC’s main document, presents cohort and case-control epidemiological studies predominately manufacturing and garment industries, as well as exposure in mobile homes to formaldehyde- containing materials.3 The main conclusions are based on studies of industrial workers, although there is a group of professionals which included pathologists, anatomists, and funeral homes workers. The data are quite contradictory due to the misclassification and the inadequate methodology of the dose-response relationship. Most data represent epidemiological studies, including cohort analyses which cannot be now repeated due to changes in manufacturing and environment.

There are conflicting literature data on this subject which cast doubt that the IRAC conclusion is balanced and can be accepted as a scientific fact. Despite attempts of scientific objective discussion, there is a trend to leave out some publications and opinions that contradict the group’s conclusion.4-9 Most references reflect data before 80th even if the articles are published after 2000. The long list of references represents limited groups of authors which publish articles in different combinations.

There is a discrepancy between the statistical epidemiological data and minimal clinical evidence from physicians who observed particular or groups of patients. Neither otolaryngology, nor other surgical manuals even mention formaldehyde as a possible ethological or contributing factor of cancer in their clinical observations. The fundamental “Cancer Principles and Practice of Oncology” do not mention formaldehyde either in carcinogenicity or in other clinical chapters (head and neck, lung).10Pathologists haven’t observed higher morbidity or mortality of colleagues and technical staff in contact with formalin. (See details at post “Formaldehyde carcinogenicity as safety concern” at Safety section).

The divide regarding formaldehyde carcinogenicity has a remote analogy with global warming/climate change. Nobody dare to challenge this notion. The deleterious effect of formaldehyde makes carcinogenicity so obvious that it is even impolite to question its credibility.

In practical sense, however, the dispute over formaldehyde carcinogenicity is meaningless at this time. We have to accept the conclusion of IARC until it is proven wrong. Moreover, there is barely a chance that such studies will be conducted in the foreseeable future. The USA regulatory agencies, the EPA and the OSHA assume formaldehyde as a potential occupational carcinogen with appropriate regulations. 1 OSHA mandated the notice in any laboratory or industrial area where formaldehyde mixtures or solutions capable of releasing formaldehyde into the air at concentrations reaching exceeding 0.1 ppm are used:” Danger: Formaldehyde: irritant and potential cancer hazard.”

Manufacturers have accepted regulation and measure improvements in the work place environment, instead of engaging in costly altercations with the EPA and lawyers, as well as sustaining public relation losses with the aggressive coverage on formaldehyde carcinogenicity subject by the mainstream media. The American Conference of Governmental Industrial Hygienists (ACGIH) has more stricter requirements for time weighted average (TWA) short-term-exposure limit (STEL) (0.3 ppm) than OSHA (2 ppm), although the recommended exposure limits do not have a legal application in the USA in opposite to OSHA. It is remarkable that the ACGIH 0.3 ppm limit is set on irritation, not carcinogenicity.

Clinical laboratories and other facilities (anatomical, research) have accepted the OSHA requirement for 8 hours time weighted average Permissible Exposure Limit (PEL) of 0.75 ppm. There is not in public domain 8 hours TWA by the ACGIH. The management of local laboratories accepts this measure without any question. The institution’s authorities would not forgive the laboratory management’s failure to meet these relatively simple requirements because there would be some consequences of accreditation which nobody needs.

This rosy picture, however, obscures very important question. The regularly scheduled monitoring reflects more or less the general environment in the work place but the devil of formaldehyde exposure is in the details of every day work practices– how the splashes and spills are handled, as well as wet specimen disposal; this is when the most overexposure occurs, but nobody monitors and even pays attention. The everyday practice occurrences of overexposure are more important than quite theoretical carcinogenicity.

During overexposure, the workers lose, temporally or permanently due to sensitization, the natural defense of the upper respiratory tract or skin. Given by evolution, both are, especially upper respiratory area (nasal mucosa, paranasal sinuses, conches) with the tiny cilia movement mechanism, very important immunological line of defense not only against pathogenic infection although the latter is the main beneficiary. (See more details in ”Formaldehyde exposure safety rationale” in the Safety section  ).

Toxicity of formaldehyde overexposure is not urban legend. Due to my silly behavior during a cleanup of a formalin spill, I lost once my voice for a week. Of course, it was a chemical injury. However, some “micro burns” occur in practice on a permanent basis. For example, when the working tissue processor is opened for some reasons (add/take out a cassette/s, check something, etc.)in formalin phase a vapor of formaldehyde from the warm formalin goes in the person’s breathing area. Separation of specimens from formalin during specimen disposal is a different example. In my pathology youth, I had many eye injuries by formalin splashes.

Regarding formaldehyde carcinogenicity everyone is entitled to his/her opinion, especially the question is unsolvable at this stage of society’s development.

In my opinion, this is an unproven concept. However, the harmful effect of formaldehyde exposure is indisputable. Efforts should be concentrated as much as possible on the prevention of negative consequences, by improving working conditions, introducing and following safe work practices. It should be made clear to everyone that personal responsibility is matter of paramount importance.

(See also posts “Monitoring formaldehyde exposure ”, “Formalin Spills and Splashes”, as well as the summarized article”Formalin safety in the surgical pathology laboratory” in the Safety section. Although the article is too long for a website, it provides a comprehensive approach to formalin safety topics that are presented in separate website’s posts. It is an “uncensored by reviewers” variant of the article which has been published in LabMedicine in 2009 )


1. Council Report. Formaldehyde.  Council on Scientific Affairs. JAMA 1989; 261:1183-1187

2.  IARC Press Release No 153, 15 June 2004

3. World Health Organization International  Agency for Research on Cancer IARC Monographs on the Evaluation Carcinogenic Risks on Humans Volume 88 , 2006 Formaldehyde Monographs Programme

4.  Collins JJ, Acquavella JF, Esmen NA: An Updated Meta-Analysis of Formaldehyde Exposure and Upper Respiratory Tract JOEM, Vol 39, Number 7, July 1997: 639-651

5.  Gardner MJ, Pannett B., Winter PD, Crudas AM.  A cohort study of workers exposed to formaldehyde in the British chemical industry: an update British Journal of Industrial Medicine 1993; 50: 827-834

6. McLaughlin JK. Formaldehyde cancer: a critical review. Int Arch Occup Environ Health (1994) 66: 295-301

7. Chang ET. Adami HO The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol. Biomarkers Prev, 2006; 15 (10); 1765-1977

8. Hauptman M, Lubin JH, Stewart PA, Hayes RB, Blair A: Mortality from solid cancers among Workers in Formaldehyde Industries. American Journal of Epidemiology, 159; (12): 1117-1130

9. C. Bosetti C, McLaughlin JK, Tarone RE, Pira E and La Vecchia C: Formaldehyde and cancer risk: a quantative review of cohort studies through 2006. Annals of Oncology 2008; 19; (1): 29-43

10. DeVita VT, Hellman S, Rosenberg SA. Cancer: Principles and Practice of Oncology.  Lippincott Williams & Wilkins 7th Ed, 2008








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4 Responses to Reflections on Formaldehyde Carcinogenicity

  1. RJ Buesa says:

    Why was it that while reading this piece I remembered those “not convinced” of clima change?

  2. You are right by noting the analogy with the climate change debate in this post. I did not want to emphasize this analogy, though mentioned it; I tried to avoid politicizing this medical issue. In the reply, I fill freer from this restrain because I have not initiated it.
    As you remember, the debate was not about climate change, but about global warming. Those “not convinced” were behind the change in the terminology from definitely measurable global warming to a vague climate change for well- known reasons due to “the inconvenient truth” of intellectual dishonesty revelations in the background of global warming studies and publications. Even if there is global warming and even if there is a human component in its acceleration, this phenomenon has been used for governmental intrusions where bureaucratic micro and macro management of industrial activity in developed countries merges with big money benefits from governmental allocations which have unlimited opportunities for corruption and political manipulation. In order for a lay person to stop these politically charged statements, I want to come closer to the analogy with formaldehyde carcinogenicity.
    The first analogy is that in both cases neither formaldehyde carcinogenicity in humans, nor global warming induced by human activities can be proven or disproven. Both depend on the progress in more efficient technology. It occurs due to the natural human drive to improve life by technological advancement. Humans will not go back.
    The second analogy is that both global warming and the fight over formaldehyde carcinogenicity require governmental regulations, a festival for bureaucracy of all stripes with a theological belief that this is the right thing to do. Who wants Venice under water or even a rare nasopharyngeal cancer?
    The most important analogy for our case is that both deflect resources and attention. Cooling the Earth increases living costs in many ways. While monitoring the work place that is a positive outcome of the cancer scare, the OSHA’s acceptable levels of long-term exposure deflect attention from other areas of indisputable formaldehyde’s harmful effects. More details about formaldehyde carcinogenicity in anatomical pathology in the post Formaldehyde Carcinogenicity as Safety Concern

    In general, it is not fair to compare the malignance for the society of the global warming alarm and the benign formaldehyde carcinogenicity delusion, but the analogy does exist.
    Thank you for the opportunity to elaborate on this controversial issue which I would not be able to publish in any peer-reviewed journal or magazine.

  3. RJ Buesa says:

    Doubts about formaldehyde carcinogenicity and the negative opinions about clima change have something very important in common: neither can be experimentally proven. This common characteristic allows a convenient route of dissent amongst those who, for very different causes, prefer to deny them.
    Remember those executives who also denied the carcinogenicity of tobacco? The same thing, it could not be experimentally proven and, like with formaldehyde, ethical reasons prevent the design of a blind experiment with “placebos” vs. formaldehyde. Does this mean that formaldehyde can be denied its dangerous condition? Yes, it can be denied because all the indicators are indirect.
    The similarity with clima change is also that you cannot design an experiment on climatic scale allowing those who deny the anthropogenic nature of clima change can say it is not true and that it is only a natural “cyclic” phenomenon.
    Those deniers point to the fact that there are records in 250,000 years old ice cores of heating and cooling periods and selectively point to this fact overlooking that those same ice cores show an accelerated increase of atmospheric carbon dioxide contents starting at the beginning of the last century.
    Those who deny indirect facts, be it formaldehyde or tobacco carcinogenicity, or the anthropogenic nature of clima change and its consequence of global warming, use the same approach: it is not tru because it cannot be demonstrated experimentally but forget to point out that those “needed controlled” experiments are either unethical or impossible.
    These are very “convenient” circumstances that give a “escape route” to those interested to deny the facts.
    Meanwhile the facts remain “shrouded” in doubt and can always be denied or questioned.
    Tell that to those suffering from cancer due to formaldehyde exposure or to the Malvinians that have already started to migrate to near islands because theirs are starting to disappear swallen by the increasing Indian ocean levels.
    Demying adverse formaldehyde effects or global warming will be seen before the end of this century as a reality reduced to the absurd.
    René J, Buesa

  4. Ivanhoe says:

    Come on “guys”. It is obvious that carcinogenicity of formalin is a reasonable assertion and an attainable evaluation within the confines of time (a human generation) and a laboratory. Perhaps 100s of years or generations will define the weight of human cause towards climate change, in addition to the obvious on-going earth recovery from the “Ice-Age”.
    There are certainly politics within medicine which hinder hard standards, and perhaps another parallel would be formalin fixation protocols with cold ischemic times and breast ancillary studies (i.e. Her2 and ER/PR receptors). “Everyone” knows that is makes little to no difference in beginning the formalin fixation time when you dunk a lumpectomy or mastectomy into 10% formalin, as it contributes little towards hindering degradation of the existing Her2 activity, UNTIL the actual lesion/soft tissue is actually exposed to formalin as close to the 60 minute ischemic period: “Oh, and by the way, it is a good idea to section through the lesion asap and return to formalin; but not as so as to constrain you to do so.” (para-ij).

    Nevermind the USA going broke redistributing our wealth toward mastering Mother Earth’s homeostasis. Nice discussion Dr. Izak over many cups of coffee.

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