Carcinogenic potential of formaldehyde in occupational settings: a critical assessment and possible impact on occupational exposure levels.
OBJECTIVE
To review epidemiological studies which led to a change in the classification of formaldehyde by the International Agency for Research on Cancer (IARC) in 2004 as well as studies published thereafter, with the objective to examine whether occupational exposure levels for formaldehyde should be adapted.


METHODS
Cohort and case-control studies investigating the association between occupational exposure to formaldehyde and nasopharyngeal cancer (NPC) and reporting estimates of formaldehyde exposure as well as the most recent meta-analyses, published after 1994, were reviewed.


RESULTS
Evidence of an association between occupational formaldehyde exposure and NPC appears debatable. Results of the cohort studied by Hauptmann et al. (Am J Epidemiol 159(12):1117-1130, 2004) were key findings in the IARC evaluation. In this study, mortality from NPC was elevated compared with that of the US general population. However, internal comparison analysis using alternative categorization revealed that none of the relative risk for NPC was statistically significantly increased in any category of exposure (Marsh and Youk in Regul Toxicol Pharmacol 42(3):275-283, 2005) and re-analyses of the data highlighted the inappropriateness of the exposure assessment used by Hauptmann et al. (Am J Epidemiol 159(12):1117-1130, 2004) and Marsh et al. (Regul Toxicol Pharmacol 47(1):59-67, 2007). Two other cohorts (Coggon et al. in J Natl Cancer Inst 95(21):1608-1615, 2003; Pinkerton et al. in Occup Environ Med 61(3)193-200, 2004) reported no increase in NPC. Two case-control studies brought some evidence of an increased risk of NPC but the assessment of exposure levels was uncertain.


CONCLUSIONS
Human studies fail to raise a convincing conclusion concerning the carcinogenicity of formaldehyde and are not helpful to delineate a possible dose-response relationship. Experimental data indicate that in rats, the carcinogenic activity of formaldehyde is associated with cytotoxic/proliferative mechanisms. Therefore protecting from these effects associated with formaldehyde exposure should be sufficient to protect from its potential carcinogenic effects, if any in humans.


CONCLUSIONS
Current occupational exposure levels to formaldehyde, set to protect against local irritation, should not be adapted.
Duhayon
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Unité de toxicologie industrielle et médecine du travail, Université catholique de Louvain, Avenue E. Mounier, 53 boite 53 02, 1200 Bruxelles, Belgium. sophie.duhayon@uclouvain.be
Hoet
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Van Maele-Fabry
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Lison
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D000395:Air Pollutants, Occupational / Q000633:toxicity*; D016022:Case-Control Studies; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D016021:Epidemiologic Studies; D005557:Formaldehyde / Q000633:toxicity*; D006801:Humans; D019570:Inhalation Exposure; D009303:Nasopharyngeal Neoplasms / Q000139:chemically induced* / Q000401:mortality; D009784:Occupational Diseases / Q000139:chemically induced* / Q000401:mortality; D016273:Occupational Exposure; D018570:Risk Assessment / Q000379:methods*
D000395:Air Pollutants, Occupational; D005557:Formaldehyde