TR 065 : Formaldehyde and Human Cancer Risks | May 1995
Formaldehyde is a natural component in all mammalian cells and because of active enzymatic pathways is rapidly detoxified. Its use by man has been long-term and widespread, finding both medical and industrial applications.
This review examines the cytologic and cytogenetic studies of workers exposed to formaldehyde and examines the epidemiologic studies on cancer risk as they relate to formaldehyde exposure. All studies reviewed were non-experimental in design and as such concerns of bias, confounding and chance must be evaluated thoroughly before any etiologic conclusion can be drawn.
The cytologic and cytogenetic studies of worker volunteers in the formaldehyde industry were inconsistent in their findings, biased in their selection of exposed and non-exposed control subjects, confounded by other exposures and not large enough to allow for the sufficient exclusion of chance. Before these studies can be taken as serious evidence they must be larger in scale, show absence of selection bias and provide proper control of confounding factors and present a detailed and informed analysis.
Epidemiologic studies of formaldehyde and human cancer risk can be divided into three major groups: formaldehyde industry workers, morticians and medical professionals, and community-based case-control studies. These three groups reflect a descending order in the likelihood of exposure, with the formaldehyde industry workers having certain, and for the most part, measured exposure. The medical professionals and morticians are likely to have some exposure with the potential for short-term high peaks in exposure. Community-based case-control studies have no certainty of exposure; all putative exposure to formaldehyde is inferred from job titles.
The cohort studies of formaldehyde industry workers provide no convincing evidence of a link with cancer. There is no evidence of an excess of nasal cancer, the neoplasm reported in animal studies. One study suggesting an association between formaldehyde and nasopharyngeal cancer has been shown to suffer from misdiagnosis and multiple comparison biases.
Studies of medical professionals and morticians report no link with nasal cancer, nasopharyngeal or lung cancer risk, sites that would come into contact with formaldehyde. Based on years of animal experiments, effects on sites distal to those exposed are not considered to be related to formaldehyde due to the highly reactive nature and rapid metabolism of this chemical. Hence the excess of colon and brain cancer and leukaemia found among professionals is not likely to be a result of their exposure to formaldehyde.
Community-based case-control studies provide the weakest evidence of all study approaches because there is no documented exposure, data for the latter is derived from job-titles. In this context it is worth noting that the case-control studies performed within cohorts of formaldehyde industry workers (nested case-control studies) were all uniform in showing no relation to formaldehyde exposure. The community-based studies failed to eliminate bias, confounding and chance as the most likely explanations of their findings. None provides convincing evidence of a causal link.
After a careful review of the cytologic, cytogenic and epidemiological studies there is an absence of evidence to support the judgement of an etiologic relationship between formaldehyde and human cancer risk. Causal criteria used by epidemiologists in evaluating an association, such as strength of an association, consistency of results across studies, dose-response effects, biologic plausibility and coherence have not been met by the studies examined in this report.