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

There was no excess mortality from leukemia when the industrial workers were compared with the general U.S. population, but a comparison with the general population may be biased. In another study, excess mortality from leukemia was found in the recent update of garment workers in the United States (Pinkerton et al. 2004). This excess was statistically significant among workers with a longer duration of exposure and follow-up. In contrast, the updated study of industrial workers in the United Kingdom did not find excess mortality from leukemia (Coggon et al. 2003). This high-quality study had sufficient size and follow-up to have reasonable power for detecting an excess of leukemia, but it did not report on peak exposures or the risk of myeloid leukemia specifically. The working group concluded, "In summary, there is strong but not sufficient evidence for a causal association between leukemia and occupational exposure to formaldehyde." This conclusion, falling between sufficient and limited evidence, was based on a consistently increased risk in studies of embalmers, funeral parlor workers, pathologists, and anatomists and was present in two of the three most informative studies of industrial workers.

Several case-control studies have investigated the relationship between formaldehyde exposure and sinonasal cancer. A pooled analysis of 12 studies showed an increased risk of adenocarcinoma in men and women thought never to have been exposed to wood dust or leather dust, with an exposure-response trend for an index of cumulative exposure (Luce et al. 2002). One other case-control study (Olsen and Asnaes 1986) and a proportionate incidence study (Hansen and Olsen 1995) showed an increased risk of sinonasal cancer, particularly squamous cell carcinoma. Against these largely positive findings, the three most informative cohort studies of industrial workers showed no excesses of sinonasal cancer (Coggon et al. 2003; Hauptmann et al. 2004; Pinkerton et al. 2004). The working group noted that most studies did not distinguish tumors as originating in the nose or sinuses; thus, an increased risk of nasal cancer would be diluted if there were no corresponding effect on the sinuses. In the case-control studies, the working group also noted the potential for confounding by wood dust exposure, which is associated with adenocarcinoma. The working group concluded that there is limited evidence that formaldehyde causes sinonasal cancer in humans.

In experimental animals, several studies have shown that inhalation exposure induces squamous cell carcinomas of the nasal cavities in rats (Albert et al. 1982; Feron et al. 1988; Gibson 1984; Kamata et al. 1997; Kerns et al. 1983; Monticello et al. 1996; Morgan et al. 1986; Sellakumar et al. 1985; Woutersen et al. 1989), although single studies in mice (Kerns et al. 1983) and hamsters (Dalbey 1982) showed no carcinogenic effects. Four studies of formaldehyde administered to rats in drinking water gave varying results: One showed an increased incidence of forestomach papillomas in male rats (Takahashi et al. 1986); a second showed an increased incidence of gastrointestinal leiomyosarcomas in female rats and in both sexes combined (Soffritti et al. 1989); a third showed increased incidences of total malignant tumors, lymphomas and leukemias, and testicular interstitial-cell adenomas in male rats (Soffritti et al. 2002); whereas a fourth did not show a carcinogenic effect (Til et al. 1989). Formaldehyde also showed cocarcinogenic effects by inhalation, ingestion, and dermal exposure (Dalbey 1982; Iverson 1986; Takahashi et al. 1986).