Meeting report: summary of IARC Monographs on formaldehyde, 2-butoxyethanol, and 1-tert-butoxy-2-propanol

Environmental Health Perspectives, Sept, 2005 by Vincent James Cogliano, Yann Grosse, Robert A. Baan, Kurt Straif, Marie Beatrice Secretan, Fatiha El Ghissassi

Working groups are selected to invite the best-qualified experts and to avoid real or apparent conflicts of interests. Consideration is given also to demographic diversity and a balanced representation of all scientific views. Each potential participant submits a Declaration of Interests [World Health Organization (WHO) 2005], which IARC assesses to determine whether there is a conflict that warrants some limitation on participation. An expert with a real or apparent conflict of interest may not serve as chairperson, draft text discussing cancer data, or participate in the evaluations. IARC strives to ensure that the working group is free from all attempts at interference, before and during the meeting. This includes lobbying, written materials, and meals or other favors offered by interested parties. Working group members are asked not to discuss the subject matter with anyone outside the meeting and to report all attempts at interference (Cogliano et al. 2004).

Results

Formaldehyde. There was a statistically significant excess of deaths from nasopharyngeal cancer in the largest and most informative cohort study of industrial workers (Hauptmann et al. 2004), with statistically significant exposure-response relationships for peak and cumulative exposure. An excess of deaths from nasopharyngeal cancer was also observed in a proportionate mortality analysis of the largest U.S. cohort of embalmers (Hayes et al. 1990), and an excess of cases of nasopharyngeal cancer was observed in a Danish study of proportionate cancer incidence among workers at companies that manufactured or used formaldehyde (Hansen and Olsen 1995). Although other cohort studies reported fewer cases of nasopharyngeal cancer than expected (Coggon et al. 2003; Pinkerton et al. 2004; Walrath and Fraumeni 1983), the working group noted that the deficits were small and the studies had low power to detect an effect on nasopharyngeal cancer. Of seven case-control studies of nasopharyngeal cancer (Armstrong et al. 2000; Hildesheim et al. 2001; Olsen et al. 1984; Roush et al. 1987; Vaughan et al. 1986, 2000; West et at. 1993), five found elevations of risk for exposure to formaldehyde. The working group considered it "improbable that all of the positive findings for nasopharyngeal cancer that were reported from the epidemiologic studies, and particularly from the large study of industrial workers in the United States, could be explained by bias or unrecognized confounding effects." The working group concluded that these studies provide "sufficient epidemiological evidence that formaldehyde causes nasopharyngeal cancer in humans."

Excess mortality from leukemia, primarily of the myeloid type, has been observed relatively consistently in six of seven studies of embalmers, funeral parlor workers, pathologists, and anatomists (Hall et al. 1991; Hayes et al. 1990; Levine et al. 1984; Logue et al. 1986; Stroup et al. 1986; Walrath and Fraumeni 1983, 1984). A recent meta-analysis found that, overall, the relative risk for leukemia in these workers was increased and did not vary significantly among studies (Collins and Lineker 2004). There had been speculation that these findings might be explained by viruses; however, the working group found little evidence that these occupations have a higher incidence of viral infections or that viruses have a causal role in myeloid leukemia. Until recently, these leukemia findings received little attention because excess leukemia had not been observed in the studies of industrial workers. There is now, however, some evidence for an association between formaldehyde exposure and leukemia in the recent updates of two of the three major industrial cohorts. A statistically significant exposure-response relationship was observed for leukemia and, particularly, for myeloid leukemia in the study of industrial workers in the United States, based on peak exposure and, to a lesser degree, on average intensity of exposure to formaldehyde (Hauptmann et al. 2003).