Formaldehyde carcinogenicity research: 30 years and counting for mode of action, epidemiology, and cancer risk assessment

Toxicologic Pathology

Volumn 41, Issue 2, 2013, Pages 181-189

  Swenberg, James A ^a   Moeller, Benjamin C ^a   Lu, Kun ^a   Rager, Julia E ^a   Fry, Rebecca C ^a   Starr, Thomas B ^a  

^a IL   (United States)

Author keywords

biomarkers; carcinogenesis; environmental toxicology; inhalation; mechanisms of toxicity; risk assessment

Indexed keywords

FORMALDEHYDE; MICRORNA;

ARTICLE; CANCER EPIDEMIOLOGY; CANCER RISK; CARCINOGEN DNA INTERACTION; CARCINOGENESIS; CARCINOGENICITY; CELL PROLIFERATION; DNA DAMAGE; DRUG CARCINOGENICITY; DRUG EFFECT; DRUG EXPOSURE; DRUG MECHANISM; EPIGENETICS; GENE EXPRESSION; HUMAN; LEUKEMIA; MUTAGENICITY; NASOPHARYNX CANCER; NONHUMAN; NOSE CARCINOMA; PRIORITY JOURNAL; RISK ASSESSMENT; SPECIES DIFFERENCE; SQUAMOUS CELL CARCINOMA;

ANIMALS; CARCINOGENICITY TESTS; ECOTOXICOLOGY; FORMALDEHYDE; HUMANS; NEOPLASMS; RISK ASSESSMENT;

RATTUS; RODENTIA;

EID: 84875712048     PISSN: 01926233     EISSN: 15331601     Source Type: Journal    
DOI: 10.1177/0192623312466459     Document Type: Article

References (43)

1. Altekruse S. F., Kosary C. L., Karcho M., Neyman N., Aminou R., Waldron W., Ruhl J., Howlader N., Tatalovich Z., Cho H., Mariotto A., Eisner M. P., Lewis D. R., Cronin K., Chen H. S., Feuer E. J., Stinchcomb D. G., Edwards B. K SEER Cancer Statistics Review, 1975-2007. Bethesda: National Cancer Institute ; 2010 :
2. Andersen M. E., Clewell H. J., Bermudez E., Dodd D. E., Willson G. A., Campbell J. L., Thomas R. S.. Formaldehyde: Integrating dosimetry, cytotoxicity, and genomics to understand dose-dependent transitions for an endogenous compound. Toxicol Sci. 2010 ; 118: 716-31
3. Bachand A. M., Mundt K. A., Mundt D. J., Montgomery R. R.. Epidemiological studies of formaldehyde exposure and risk of leukemia and nasopharyngeal cancer: A meta-analysis. Crit Rev Toxicol. 2010 ; 40: 85-100
4. Beane Freeman L. E., Blair A., Lubin J. H., Stewart P. A., Hayes R. B., Hoover R. N., Hauptmann M.. Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries: The National Cancer Institute cohort. J Nat Cancer Inst. 2009 ; 101: 751-61
5. Bosetti C., McLaughlin J. K., Tarone R. E., Pira E., La V. C.. Formaldehyde and cancer risk: A quantitative review of cohort studies through 2006. Ann Oncol. 2008 ; 19: 29-43
6. Casanova M., Morgan K. T., Gross E. A., Moss O. R., Heck H. A.. DNA-protein cross-links and cell replication at specific sites in the nose of F344 rats exposed subchronically to formaldehyde. Fundam Appl Toxicol. 1994 ; 23: 525-36
7. Casanova-Schmitz M., Starr T. B., Heck H. D.. Differentiation between metabolic incorporation and covalent binding in the labeling of macromolecules in the rat nasal mucosa and bone marrow by inhaled [14C]- and [3H]-formaldehyde. Toxicol Appl Pharmacol. 1984 ; 76: 26-44
8. Chang J. C. F., Gross E. A., Swenberg J. A., Barrow C. S.. Nasal cavity deposition, histopathology, and cell proliferation after single or repeated formaldehyde exposures in B6C3F1 mice and F-344 rats. Toxicol Appl Pharmacol. 1983 ; 68: 161-76
9. Coggon D., Harris E. C., Poole J., Palmer K. T.. Extended follow-up of a cohort of British chemical workers exposed to formaldehyde. J Natl Cancer Inst. 2003 ; 95: 1608-15
10. Cohn M. S. Revised Carcinogenic Risk Assessment of Urea-Formaldehyde Foam Insulation: Estimates of Cancer Risk due to Inhalation of Formaldehyde Released by UFFI. Oct. 26. 1981 :
11. Collins J. J., Acquavella J. F., Esmen N. A.. An updated meta-analysis of formaldehyde exposure and upper respiratory tract cancers.. 1997 ; 39: 639-51
12. Review of the Environmental Protection Agency's Draft IRIS Assessment of Formaldehyde. Washington, DC: The National Academies Press ; 2011.
13. Conolly R. B., Kimbell J. S., Janszen D., Schlosser P. M., Kalisak D., Preston J., Miller F. J.. Biologically motivated computational modeling of formaldehyde carcinogenicity in the F344 rat. Toxicol Sci. 2003 ; 75: 432-47
14. Conolly R. B., Kimbell J. S., Janszen D., Schlosser P. M., Kalisak D., Preston J., Miller F. J.. Human respiratory tract cancer risks of inhaled formaldehyde: Dose-response predictions derived from biologically-motivated computational modeling of a combined rodent and human dataset. Toxicol Sci. 2004 ; 82: 279-96
15. Duhayon S., Hoet P., Van Maele-Fabry G., Lison D.. Carcinogenic potential of formaldehyde in occupational settings: A critical assessment and possible impact on occupational exposure levels. Int Arch Occup Environ Health. 2008 ; 81: 695-710
16. Filipowicz W., Bhattacharyya S. N., Sonenberg N.. Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight?. Nat Rev Genet. 2008 ; 9: 102-14
17. Hauptmann M., Lubin J. H., Stewart P. A., Hayes R. B., Blair A.. Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries. J Nat Cancer Inst. 2003 ; 95: 1615-23
18. Hauptmann M., Lubin J. H., Stewart P. A., Hayes R. B., Blair A.. Mortality from solid cancers among workers in formaldehyde industries. Am J Epidemiol. 2004 ; 159: 1117-30
19. Hauptmann M., Stewart P. A., Lubin J. H., Beane Freeman L. E., Hornung R. W., Herrick R. F., Hoover R. N., Fraumeni J. F., Blair A., Hayes R. B.. Mortality from lymphohematopoietic malignancies and brain cancer among embalmers exposed to formaldehyde. J Nat Cancer Inst. 2009 ; 101: 1696-708
20. Heck H. D., Casanova M., Starr T. B.. Formaldehyde toxicity - new understanding. Crit Rev Toxicol. 1990 ; 20: 397-426
21. Formaldehyde, 2-Butoxyethanol and 1-tert-Butoxypropan-2-ol. IARC Monogr Eval Carcinog Risks Hum. 2006 ; 88: 1-287
22. A review of human carcinogens. Part F: Chemical agents and related occupations. Lyon, France: IARC ; 2012: 401-35.
23. Izzotti A., Calin G. A., Arrigo P., Steele V. E., Croce C. M., De Flora S.. Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J. 2009 ; 23: 806-12
24. Kerns W. D., Pavkov K. L., Donofrio D. J., Gralla E. J., Swenberg J. A.. Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure. Cancer Res. 1983 ; 43: 4382-92
25. Kimbell J. S., Overton J. H., Subramaniam R. P., Schlosser P. M., Morgan K. T., Conolly R. B., Miller F. J.. Dosimetry modeling of inhaled formaldehyde: Binning nasal flux predictions for quantitative risk assessment. Toxicol Sci. 2001 ; 64: 111-21
26. Kimbell J. S., Subramaniam R. P., Gross E. A., Schlosser P. M., Morgan K. T.. Dosimetry modeling of inhaled formaldehyde: Comparisons of local flux predictions in the rat, monkey, and human nasal passages. Toxicol Sci. 2001 ; 64: 100-10
27. Lu K., Boysen G., Gao L., Collins L. B., Swenberg J. A.. Formaldehyde-induced histone modifications. in vitro. Chem Res Toxicol. 2008 ; 21: 1586-93
28. Lu K., Collins L. B., Ru H., Bermudez E., Swenberg J. A.. Distribution of DNA adducts caused by inhaled formaldehyde is consistent with induction of nasal carcinoma but not leukemia. Toxicol Sci. 2010 ; 116: 441-51
29. Lu K., Moeller B., Doyle-Eisele M., McDonald J., Swenberg J. A.. Molecular dosimetry of N2-hydroxymethyl-dG DNA adducts in rats exposed to formaldehyde. Chem Res Toxicol. 2011 ; 24: 159-61
30. Lu K., Ye W., Zhou L., Collins L. B., Chen X., Gold A., Ball L. M., Swenberg J. A.. Structural characterization of formaldehyde-induced cross-links between amino acids and deoxynucleosides and their oligomers. J Am Chem Soc. 2010 ; 132: 3388-99
31. Marsh G. M., Youk A. O., Buchanich J. M., Erdal S., Esmen N. A.. Work in the metal industry and nasopharyngeal cancer mortality among formaldehyde-exposed workers. Regul Toxicol Pharmacol. 2007 ; 48: 308-19
32. Moeller B. C., Lu K., Doyle-Eisele M., McDonald J., Gigliotti A., Swenberg J. A.. Determination of N2-hydroxymethyl-dG adducts in nasal epithelium and bone marrow of non-human primates following 13CD2-formaldehyde inhalation exposure. Chem Res Toxicol. 2011 ; 24: 162-64
33. Monticello T. M., Morgan K. T., Hurtt M. E.. Unit length as the denominator for quantitation of cell proliferation in nasal epithelia. Toxicol Pathol. 1990 ; 18: 24-31
34. Monticello T. M., Swenberg J. A., Gross E. A., Leininger J. R., Kimbell J. S., Seilkop S., Starr T. B., Gibson J. E., Morgan K. T.. Correlation of regional and nonlinear formaldehyde-induced nasal cancer with proliferating populations of cells. Cancer Res. 1996 ; 56: 1012-22
35. accessed 10 may 2011:
36. Pinkerton L. E., Hein M. J., Stayner L. T.. Mortality among a cohort of garment workers exposed to formaldehyde: An update. Occup Environ Med. 2004 ; 61: 193-200
37. Rager J. E., Smeester L., Jaspers I., Sexton K. G., Fry R. C.. Epigenetic changes induced by air toxics: Formaldehyde exposure alters miRNA expression profiles in human lung cells. Environ Health Perspect. 2011 ; 119 :
38. Starr T. B., Gibson J. E.. The mechanistic toxicology of formaldehyde and its implications for quantitative risk estimation. Annu Rev Pharmacol Toxicol. 1985 ; 25: 745-67
39. Starr T. B., Swenberg J. A.. A novel bottom-up approach to bounding low-dose human cancer risks from chemical exposures. Regul Toxicol Pharmacol. 2012 ;:
40. Swenberg J. A., Kerns W. D., Mitchell R. I., Gralla E. J., Pavkov K. L.. Induction of squamous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor. Cancer Res. 1980 ; 40: 3398-402
41. Part IV: Consumer Product Safety Commission ban of urea formaldehyde foam insulation, withdrawal of proposed labeling rule, and denial of petition to issue a standard. Fed Regist. 1982 ; 47: 14366-419
42. Formaldehyde: Determination of significant risk. Fed Regist. 1984 ; 49: 21870-898
43. accessed 9 june 2010 :