Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (776 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A highly reactive aldehyde gas formed by oxidation or incomplete combustion of hydrocarbons. In solution, it has a wide range of uses: in the manufacture of resins and textiles, as a disinfectant, and as a laboratory fixative or preservative. Formaldehyde solution (formalin) is considered a hazardous compound, and its vapor toxic. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p717)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Methanal; Oxomethane; Formol; Formalin.
Where it fits in the MeSH classification
- Broader topics
- Aldehydes
- Narrower topics
- Formocresols
Research landscape
PubMed indexes 24,546 records tagged with the MeSH heading “Formaldehyde” (counts retrieved 2026-10-31). 3,199 of them (13.0%) were published from 2020 onward, and the busiest period so far is through 1999 with 12,059 records.
Reviews account for 933 records (3.8%) and meta-analyses for 60. Randomized controlled trials number 198 (0.8%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 12,059 |
| 2000-2009 | 4,147 |
| 2010-2019 | 5,141 |
| 2020 onward | 3,199 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 933 | 3.8% |
| Meta-analyses | 60 | 0.2% |
| Randomized controlled trials | 198 | 0.8% |
Method: PubMed query "Formaldehyde"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Two Aldehyde Clearance Systems Are Essential to Prevent Lethal Formaldehyde Accumulation in Mice and Humans | 2020 | Research article Design not recorded in structured metadata | 154 | cc by PMID 33147438 · DOI · PMC7758861 |
| The mutational signatures of formalin fixation on the human genome | 2022 | Research article Design not recorded in structured metadata | 111 | cc by PMID 36068219 · DOI · PMC9448750 |
| Mass spectrometry reveals the chemistry of formaldehyde cross-linking in structured proteins | 2020 | Research article Design not recorded in structured metadata | 106 | cc by PMID 32561732 · DOI · PMC7305180 |
| Growth and formaldehyde degradation of photoheterotrophic Methylobacterium within radiation fogs | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 42112827 · DOI · PMC13251464 |
Two Aldehyde Clearance Systems Are Essential to Prevent Lethal Formaldehyde Accumulation in Mice and Humans [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Reactive aldehydes arise as by-products of metabolism and are normally cleared by multiple families of enzymes.
- Closing excerpt
- Endogenous formaldehyde clearance alone is therefore critical for hematopoiesis and in limiting mutagenesis in somatic tissues.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (139 words)
Reactive aldehydes arise as by-products of metabolism and are normally cleared by multiple families of enzymes. We find that mice lacking two aldehyde detoxifying enzymes, mitochondrial ALDH2 and cytoplasmic ADH5, have greatly shortened lifespans and develop leukemia. Hematopoiesis is disrupted profoundly, with a reduction of hematopoietic stem cells and common lymphoid progenitors causing a severely depleted acquired immune system. We show that formaldehyde is a common substrate of ALDH2 and ADH5 and establish methods to quantify elevated blood formaldehyde and formaldehyde-DNA adducts in tissues. Bone-marrow-derived progenitors actively engage DNA repair but also imprint a formaldehyde-driven mutation signature similar to aging-associated human cancer mutation signatures. Furthermore, we identify analogous genetic defects in children causing a previously uncharacterized inherited bone marrow failure and pre-leukemic syndrome. Endogenous formaldehyde clearance alone is therefore critical for hematopoiesis and in limiting mutagenesis in somatic tissues.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33147438 · DOI · PMC7758861
The mutational signatures of formalin fixation on the human genome [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Clinical archives of patient material near-exclusively consist of formalin-fixed and paraffin-embedded (FFPE) blocks.
- Closing excerpt
- FFPEsig thus provides an opportunity to unlock additional clinical potential of archival patient tissues.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (165 words)
Clinical archives of patient material near-exclusively consist of formalin-fixed and paraffin-embedded (FFPE) blocks. The ability to precisely characterise mutational signatures from FFPE-derived DNA has tremendous translational potential. However, sequencing of DNA derived from FFPE material is known to be riddled with artefacts. Here we derive genome-wide mutational signatures caused by formalin fixation. We show that the FFPE-signature is highly similar to signature 30 (the signature of Base Excision Repair deficiency due to NTHL1 mutations), and chemical repair of DNA lesions leads to a signature highly similar to signature 1 (clock-like signature due to spontaneous deamination of methylcytosine). We demonstrate that using uncorrected mutational catalogues of FFPE samples leads to major mis-assignment of signature activities. To correct for this, we introduce FFPEsig, a computational algorithm to rectify the formalin-induced artefacts in the mutational catalogue. We demonstrate that FFPEsig enables accurate mutational signature analysis both in simulated and whole-genome sequenced FFPE cancer samples. FFPEsig thus provides an opportunity to unlock additional clinical potential of archival patient tissues.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36068219 · DOI · PMC9448750
Mass spectrometry reveals the chemistry of formaldehyde cross-linking in structured proteins [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Whole-cell cross-linking coupled to mass spectrometry is one of the few tools that can probe protein-protein interactions in intact cells.
- Closing excerpt
- These findings enhance the use of formaldehyde cross-linking and mass spectrometry for structural studies.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (146 words)
Whole-cell cross-linking coupled to mass spectrometry is one of the few tools that can probe protein-protein interactions in intact cells. A very attractive reagent for this purpose is formaldehyde, a small molecule which is known to rapidly penetrate into all cellular compartments and to preserve the protein structure. In light of these benefits, it is surprising that identification of formaldehyde cross-links by mass spectrometry has so far been unsuccessful. Here we report mass spectrometry data that reveal formaldehyde cross-links to be the dimerization product of two formaldehyde-induced amino acid modifications. By integrating the revised mechanism into a customized search algorithm, we identify hundreds of cross-links from in situ formaldehyde fixation of human cells. Interestingly, many of the cross-links could not be mapped onto known atomic structures, and thus provide new structural insights. These findings enhance the use of formaldehyde cross-linking and mass spectrometry for structural studies.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32561732 · DOI · PMC7305180
Growth and formaldehyde degradation of photoheterotrophic Methylobacterium within radiation fogs [4]
Abstract reading summary — source excerpts
- Opening excerpt
- The atmosphere contains thousands to millions of bacterial cells per cubic meter.
- Closing excerpt
- , show that they are a hub of active detoxification of atmospheric formaldehyde and likely growing in situ on the basis of heterotrophic or photoheterotrophic metabolism of volatile C1 compounds, with implications for atmospheric chemistry and fog harvesting as sources of freshwater.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (326 words)
The atmosphere contains thousands to millions of bacterial cells per cubic meter. However, it remains unclear if microbes are at all active or growing in situ or whether they are merely being transported in an inactive state. Based on the analyses of 32 overland radiation fog events over a 2-year period, we show that fog waters, with bacterial concentrations similar to those in continental or marine bodies of water, contain microbiomes well differentiated in composition from those in the dry aerosol microbiomes that occur locally before, during, or after fog events. They are consistently and strongly enriched in photoheterotrophic Methylobacterium species, suggesting that fog populations may be metabolizing volatile C1 compounds in situ, although phototrophy seems much less important. Indeed, metabolically active bacteria in the fog, and representative isolates of the main field populations, can degrade formaldehyde at unprecedently high rates; most of this activity seems to play a detoxification role. The increase in bacterial aerobiome counts upon intervening fog events, the dependence of microbial concentration on ambient temperature, the increases in cell size and frequency of dividing cells in fog water with respect to cells in interstitial aerosols of fogs, in addition to their metabolic capacity, all suggest that the fog water microbiome is actually growing. Consequently, droplets of atmospheric water should be considered a potential aquatic microhabitat. Our results highlight the fog microbiome's role in atmospheric chemistry and have implications for fog harvesting as a source of fresh water for human use.ImportanceWhile bacteria are common in the atmosphere, their activity in situ has remained unclear. Using stagnant radiation fogs as new study systems where sampling is optimal, the dynamics, composition, cellular characteristics, and metabolic rates of fog water microbiomes, dominated by Methylobacterium sp., show that they are a hub of active detoxification of atmospheric formaldehyde and likely growing in situ on the basis of heterotrophic or photoheterotrophic metabolism of volatile C1 compounds, with implications for atmospheric chemistry and fog harvesting as sources of freshwater.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42112827 · DOI · PMC13251464
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Formaldehyde fixation [5]
- Research article Formaldehyde crosslinking: a tool for the study of chromatin complexes [6]
- Research article Formaldehyde in China: production, consumption, exposure levels, and health effects [7]
- Research article Formaldehyde exposure and leukemia: a new meta-analysis and potential mechanisms [8]
- Research article Reproductive and developmental toxicity of formaldehyde: a systematic review [9]
- Research article The orofacial formalin test [10]
References
- Dingler FA, Wang M, Mu A, Millington CL, Oberbeck N, Watcham S, et al.. Two Aldehyde Clearance Systems Are Essential to Prevent Lethal Formaldehyde Accumulation in Mice and Humans. . 2020. PMID 33147438 · DOI · PMC7758861
- Guo Q, Lakatos E, Bakir IA, Curtius K, Graham TA, Mustonen V. The mutational signatures of formalin fixation on the human genome. . 2022. PMID 36068219 · DOI · PMC9448750
- Tayri-Wilk T, Slavin M, Zamel J, Blass A, Cohen S, Motzik A, et al.. Mass spectrometry reveals the chemistry of formaldehyde cross-linking in structured proteins. . 2020. PMID 32561732 · DOI · PMC7305180
- Cao TTT, Herckes P, Straub D, Sarkar S, Garcia-Pichel F. Growth and formaldehyde degradation of photoheterotrophic Methylobacterium within radiation fogs. . 2026. PMID 42112827 · DOI · PMC13251464
- Fox CH, Johnson FB, Whiting J, Roller PP. Formaldehyde fixation. J Histochem Cytochem. 1985. PMID 3894502 · DOI
- Hoffman EA, Frey BL, Smith LM, Auble DT. Formaldehyde crosslinking: a tool for the study of chromatin complexes. J Biol Chem. 2015. PMID 26354429 · DOI · PMC4646298
- Tang X, Bai Y, Duong A, Smith MT, Li L, Zhang L. Formaldehyde in China: production, consumption, exposure levels, and health effects. Environ Int. 2009. PMID 19589601 · DOI
- Zhang L, Steinmaus C, Eastmond DA, Xin XK, Smith MT. Formaldehyde exposure and leukemia: a new meta-analysis and potential mechanisms. Mutat Res. 2009. PMID 18674636 · DOI
- Duong A, Steinmaus C, McHale CM, Vaughan CP, Zhang L. Reproductive and developmental toxicity of formaldehyde: a systematic review. Mutat Res. 2011. PMID 21787879 · DOI · PMC3203331
- Raboisson P, Dallel R. The orofacial formalin test. Neurosci Biobehav Rev. 2004. PMID 15172765 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.