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








Controversy of Infection Exposure in Surgical Pathology

While working in anatomical pathology in different positions, I gradually developed more serious attitude towards many aspects of safety, especially infectious exposure. This change occurred in parallel with changes in the surgical pathology laboratory environment.

Specimens are more often grossed when in the fresh state. The amount of frozen sections has increased dramatically. Central air-conditioning is a friend but it might be an enemy if the around pathogenic microorganisms are dispersed in aerosol form in the case that the laboratory rooms are not meticulously cleaned by “scheduled” housekeeping.

On the other hand, are not the harmful effects of infection exposure in the surgical pathology laboratory exaggerated? Do we have sufficient data to support the protective measures such as wearing PPE that cost money and impose “hardship” while wearing them? These questions cannot be dismissed without further clarification, but there is a controversy. We do not have data of increased infectious diseases in the surgical pathology laboratory 1,2,3,4,5.

In fact, microbiology laboratory data are the focus of the most biosafety literature.  It has been reported that the risk for laboratory-acquired infections in the microbiology laboratory is higher than that for the general population. However, these data cannot be extrapolated to the surgical pathology laboratory for the obvious reason that the latter does not handle microorganism cultures. In a surgical pathology laboratory, the infectious material is dispersed at incomparably lower concentrations, although, unfortunately, in the potentially dangerous aerosol form.

In the surgical pathology laboratory, the clarification of the controversy will be never completed for two reasons. First, the amount of infectious material might not be enough to generate a clinically apparent disease that can be included in significant statistics. Second, fortunately, the OSHA requirements will prevent laboratories from collecting data for statistically reliable cohort studies. If a laboratory worker contracts tuberculosis (TB), a single occurrence would not prove anything.  I performed dozens of autopsies on cadavers with cavernous lung tuberculosis wearing only a lab coat and gloves on. I remained TB negative; nevertheless, this does not suggest that TB encounters are harmless.

There might be some disputable approaches to the effects of infection exposure in the surgical pathology laboratory (see in “Immunological perspective of infection exposure in surgical pathology laboratory” at the link Safety).

Does the controversy matter? While working in the surgical pathology laboratory, it does not make sense to risk exposure to infection. Implementation of the OSHA Bloodborne Pathogens Standard through rational work practices with personal responsibility is the key.

(See “OSHA standard for infection exposure in the surgical pathology laboratory“, “Prevention of infection exposure during frozen section“, “Bone cutting safety“, “Bloody” specimens as safety concern“, as well as the summarized article “Prevention of infection exposure in the surgical pathology laboratory” at the Safety section. Although the article is too long for a website format, it allows the reader to see the entire picture of prevention infection exposure in the surgical pathology laboratory.


1. Pike RM. Laboratory-associated infection: incidence, fatalities, causes, and prevention. Annu Rev Microb. 1979; 33: 41-66.

2. Sewell DL. Laboratory associated infections and biosafety. Clin Microbiology Rev. 1995; 8: 389-405.

3  Walker D and Campbell D.  A survey of infections in United Kingdom laboratories, 1994-1995. J Clin Pathol. 1999; 52: 415-418.

4. Lim PL, Kurup A, Gopalakrishna G. et al. Laboratory-acquired severe acute respiratory syndrome. N Engl J Med. 2004; 350:1740-5.

5. Singh K. Laboratory-Acquired Infections. Clin Infect Disease. 2009; Jul 1; 49(1):142-7.


Wet Specimen Disposal in the Surgical Pathology Laboratory

This post is a continuation of the reply to a visitor’s letter (see the comment to the article Realm in the Perspectives in Grossing Technology section and my reply to the comment). For some reasons, the specimen and formalin disposal subject was limited to two sentences in my article A Pragmatic Approach to Formalin Safety in Anatomical Pathology. LabMedicine 2009 Vol. 40 (12):740-746. It is time to bring up this question at the Grossing Technology and Beyond blog.

Every institution has its own protocol for keeping wet specimens as well as a particular schedule and mode of disposal. Most laboratories keep it on the active shelf for a month, some for three month-the time period that is sufficient for diagnosis, however, in some cases, it is requested that the specimen be kept on a prolonged or permanent basis. Incidentally, in autopsies, the material is usually kept at least for a year, unless a longer term is specified. Shelves do not need special hood/fan ventilation. Specimens do not generate formaldehyde vapors if the container is properly closed. The exposure occurs only during manipulation

There are two options for disposal: in the laboratory or outside it (in the morgue, special room, etc.). Large laboratories prefer the latter option.

Safety concerns are evident in the following three aspects of wet specimen disposal: 1. Separation of the specimen from fixative, in most cases formalin; 2. Formalin neutralization with or without recycling; 3. Specimen storage and disposal. This post will discuss only the first aspect, as an extended response to the comment.  Both formalin handling and specimen storage will be presented in separate articles: first in the Safety section, the second in Perspectives in Grossing Technology section.

Separation of the specimen from formalin is a common practice because most disposal companies request this. Separating of the specimen from the fixative is potentially the most significant encounter with formalin as far as safety is concerned. Formaldehyde’s harmful effect occurs due to a high concentration of evaporating formalin, when formaldehyde saturates the laboratory environment and is in close proximity to the breathing area of the worker.

If formalin /formaldehyde’s carcinogenicity is not beyond a reasonable doubt, quite the opposite, and its harmfulness on general heath has also has not been proven (this issues require separate discussion), its local damaging effect is indisputable. Formalin works as local fixative, that eliminates the first line of defense in infection exposure, creates allergies, and generates chronic irritation of the upper respiratory tract, especially nasopharygeal area.   During specimen disposal the individual is vulnerable, but this often goes unnoticed and slips between OSHA regulations because nobody does any measurements at time except on rare occasions as by the author of the comment on my articles and the post on this subject.

Let me quote from his letter.

It’s interesting also that no other lab/hospital in the large metro area is worried about this “bolus” exposure. My belief is their IH monitoring has not been granular enough to monitor tasks … they might simply be putting on a passive dosimeter for 8-hrs and call that good

He is exactly right.

Unfortunately, the standard management approach to monitoring would not work either, even if the monitoring measurement were done. The ACGIH exposure limit is not achievable in most real- life situations, but an OSHA TWA STEL of 2 ppm is not appropriate because 15 minute test cannot be applied to prolonged work when the cumulative effect of formaldehyde exposure starts. Furthermore, the ACGIH’s irritation limit is also not useful because the accommodation is accomplished due to fixation (really) of the receptors of the upper respiratory tract, especially the nasopharyngeal area. Respirators are not a solution, but standard PPE accompanied by enhanced ventilation of a modified grossing station can make a difference.

Besides absolutely obligatory OSHA requirement of PPE (protective gown, apron, safety glasses , and a mask), the procedure requires a large table space, corrosion resistant metallic surface, easy availability of water/sink/drain, permanently running water to increase humidity, and more intensive than at the regular grossing station ventilation. A separate special room is definitely desirable. It’s not enough to make a ventilation hood for specimen disposal. There should be a comprehensive approach that, of course, includes local ventilation.

Similar requirements are involved in grossing bones such as large firm corrosive resistant table, enhanced ventilation, and a separate place in the grossing room.

Bone specimens arrive at the surgical pathology laboratory periodically; they are not “rush” specimens and can be combined together for processing, especially keeping in mind the more strict requirements of PPE.

The TBJ Inc. company manufactures a specialized Bone Grossing Table (BGT) For full disclosure, I participated in the development of the table.

Large and even middle size laboratories, in my view, should have a bone grossing/specimen disposal station, preferably located in a separate room. New build or remodeled laboratories should include such a complex in the project. Pathology departments of large hospitals, especially in academic institutions have autopsy divisions that need to disposal of postmortem materials. Brain washing (literally) should also be done after prolonged formalin fixation. The Bone Grossing/ Specimen Disposal stations can be a solution for an effective and safe work place, killing two, perhaps, three, birds with one stone.

Again, this post is only a part of the comprehensive approach to the specimen disposal. See also the article Specimen Storage in the Surgical Pathology Laboratory in the section Perspectives in Grossing Technology.