In April 2022, the Environmental Protection Agency’s (EPA) IRIS program released a draft updated review on toxic effects of formaldehyde, a review it had been holding back since 2016. In it, the EPA directly links exposure to inhaled formaldehyde with leukemia and other lymphohematopoietic (LHP) cancers, and concludes the relationship is causal.
A number of scientific experts have questioned this conclusion based on an insufficiency of causal evidence, including the absence of mechanistic plausibility (Checkoway, et al, 2012; Anderson, M., et al, 2019; Mundt, K., et al, 2017).
It is important to take a deep look at the methods EPA is using to make these causal claims. The National Toxicology Program at NIH did not draw such a conclusion about formaldehyde and leukemia as recently as a year ago. In 2011, EPA was criticized by the National Academies of Sciences (NAS) for the less-than-rigorous methods used in its assessment of formaldehyde at the time.
“Overall, the committee found that EPA’s draft assessment was not prepared in a logically consistent fashion, lacks clear links to an underlying conceptual framework and does not sufficiently document methods and criteria used to identify evidence for selecting and evaluating studies,” NAS said, according to an article in The New York Times.
The latest EPA draft review underwent a period of public comment over the summer of 2022, and NAS is currently holding a series of expert meetings to, “… assess whether EPA’s draft document adequately and transparently evaluated the scientific literature, used appropriate methods to synthesize the current state-of-the-science, and presented conclusions regarding the hazard identification analysis and dose-response analysis of formaldehyde that are supported by the scientific evidence.”
Notably, there has been some criticism of the NAS panel makeup, by industry as well as scientists, citing possible conflicts of interest in the experts chosen to do the review.
The Center is funding additional research on formaldehyde and LHP cancers
To help bring clarity to the dispute over causal claims surrounding formaldehyde and leukemia and other LHP cancers, the Center will be funding a systematic review of top studies examining a relationship between myeloid leukemia and other LHP cancers, and exposure to inhaled formaldehyde. We will accept proposals until February 1st and plan to make the awards quickly, after an independent peer review panel scores them.
The work will begin in March and be completed by August. More information can be found here.
EPA expects to release the new formaldehyde review in the fall of this year, and there will always be criticism from interested parties, including industry and environmental advocates and tort lawyers. Let’s see what the NAS panel concludes, looking carefully at their methods. And of course, we will look at the EPA report in its final form. Hopefully, rigorous science will carry the day.
What is formaldehyde?
The U.S. Environmental Protection Agency (EPA) describes formaldehyde as a colorless gas with a strong odor that is flammable at room temperatures. It is found in thousands of building materials such as composite wood products, for example plywood and insulation. In addition, it is found in a wide range of paper products and household products, including glues, fabrics, fabric softeners, paints and other finishings. Formaldehyde is used as a preservative in medicines, cosmetics, and dishwashing liquid. It can also be found in herbicides and pesticides. Because it is a byproduct of combustion, formaldehyde is found in emissions from fuel-burning appliances such as stoves and space heaters, as well as cigarette smoke (EPA, 2022).
Formaldehyde also goes by different names, including methanal, methylene oxide, oxymethylene, methylaldehyde, and oxomethane. An interesting fact—and one that is not always mentioned—is that formaldehyde is not a substance foreign to many forms of life. It is produced endogenously, in small amounts, as part of normal biological processes in plants, animals, and humans, according to the Agency for Toxic Substances and Disease Registry, a part of the U.S. Department of Health and Human Services (ATSDR, 2020).
Why is formaldehyde exposure a concern?
Formaldehyde has been studied and monitored by agencies and regulators throughout the world since the mid-1800s when its commercial and industrial use began. Those studies have shown it is toxic to humans at certain exposure levels when inhaled. Low-levels can cause irritation of the eyes, nose, throat, airways, and skin, especially in sensitive individuals (i.e., children, seniors, people with asthma). High levels of formaldehyde exposure over many years have been associated with rare nose and throat cancers in workers exposed to it on the job (ATSDR, 2020; IARC,2006).
While formaldehyde’s relationship to the health hazards and cancers mentioned above are not new or controversial ideas, there is no consensus over whether or not exposure to inhaled formaldehyde is a causal factor for leukemia, including myeloid leukemia and other LHP cancers.
In 2006, the International Agency for Research on Cancer (IARC) stated that there was insufficient evidence of a causal link between formaldehyde inhalation and leukemia. However, in their 2018 update this was changed to, “…epidemiological evidence [emphasis added] provides support for a causal connection between occupational exposure to formaldehyde and leukemia.” The fact that the IARC notes epidemiological evidence to support the notion of a causal connection raises some questions, as it should in all cases where cause is said to be determined from observational studies.
In contrast, the U.S. National Toxicology Program (part of the National Institute on Environmental Health Sciences at the National Institutes of Health) has prudently not jumped to make causation claims in the case of inhaled formaldehyde and leukemia. Its most recent report only suggests an association between the two (National Toxicology Program, 2021).
Public health and environmental policy should be rooted in strong science. In order to keep citizens safe and the environment healthy without causing undue economic disruption, this discrepancy surrounding the health effects of formaldehyde must be addressed.
Agency for Toxic Substances and Disease Registry. Toxicological Profile for Formaldehyde. https://www.atsdr.cdc.gov/toxprofiles/tp111.pdf. Accessed 1 June 2020.
Anderson, M.E., Robinan, P. Robinan Gentry, Swenberg, J., Mundt, K., White, K. Thompson, C. Bus, J., Sherman, J., Greim, H., Bolt, H., Marsh, G., Checkoway, H., Coggon, D., Clewell, H. Considerations for refining the risk assessment process for formaldehyde: Results from an interdisciplinary workshop, Regulatory Toxicology and Pharmacology, Volume 106, 2019, Pages 210-223. ISSN 0273-2300. https://doi.org/10.1016/j.yrtph.2019.04.015.
Checkoway H, Boffetta P, Mundt DJ, Mundt KA. Critical review and synthesis of the epidemiologic evidence on formaldehyde exposure and risk of leukemia and other lymphohematopoietic malignancies. Cancer Causes Control. 2012;23(11):1747–66. https://doi.org/10.1007/s10552-012-0055-2.
Environmental Protection Agency (EPA) (2022) https://www.epa.gov/formaldehyde
International Agency for Research on Cancer. Monograph on Formaldehyde (2018) https://monographs.iarc.who.int/wp-content/uploads/2018/06/mono100F-29.pdf
International Agency for Research on Cancer (2006). Formaldehyde, 2-butoxyethanol and 1-tert- butoxypropan-2-ol. IARC Monogr Eval Carcinog Risks Hum, 88: 1–478. PMID:17366697
Mundt, K.A., A.E. Gallagher, L.D. Dell, E.A. Natelson, P. Boffetta, P.R. Gentry, Does occupational exposure to formaldehyde cause hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells? Crit. Rev. Toxicol., 47 (7) (2017), pp. 592-602, 10.1080/10408444.2017.1301878
National Toxicology Program, Formaldehyde, Report on Carcinogens. Fifteenth Edition. Research Triangle Park, NC National Institute of Environmental Health and Safety, 2021.
Swenberg JA, Moeller BC, Lu K, Rager JE, Fry RC, Starr TB. Formaldehyde carcinogenicity research: 30 years and counting for mode of action, epidemiology, and cancer risk assessment. Toxicol Pathol. 2013;41(2):181–9. https://doi.org/10.1177/0192623312466459.