Summary of Data Reported and Evaluation

The relationship between nasopharyngeal cancer and exposure to formaldehyde has also been investigated in seven case–control studies, five of which found elevated risks for overall exposure to formaldehyde or in higher exposure categories, including one in which the increase in risk was statistically significant; three studies (two of which have been published since the last monograph) found higher risks among subjects who had the highest probability, level or duration of exposure.

In the largest and most informative cohort study of industrial workers exposed to formaldehyde, a statistically significant excess of deaths from nasopharyngeal cancer was observed in comparison with the US national population, 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 US cohort of embalmers and in a Danish study of proportionate cancer incidence among workers at companies that used or manufactured formaldehyde. In three other cohort studies of US garment manufacturers, British chemical workers and US embalmers, cases of nasopharyngeal cancer were fewer than expected, but the power of these studies to detect an effect on nasopharyngeal cancer was low and the deficits were small.

Leukaemia

Excess mortality from leukaemia has been observed relatively consistently in six of seven studies of professional workers (i.e. embalmers, funeral parlour workers, pathologists and anatomists). A recently published meta-analysis of exposure to formaldehyde among professionals and the risk for leukaemia reported increased overall summary relative risk estimates for embalmers, and for pathologists and anatomists, which did not vary significantly between studies (i.e. the results were found to be homogeneous). The excess incidence of leukaemia seen in several studies appeared to be predominantly of a myeloid type. There has been speculation in the past that these findings might be explained by exposures to viruses that are experienced by anatomists, pathologists and perhaps funeral workers. However, there is currently little direct evidence that these occupations have a higher incidence of viral infections than that of the general population or that viruses play a causal role in myeloid leukaemia. Professionals may also be exposed to other chemicals, but they have no material exposure to known leukaemogens. Furthermore, the exposure to other chemicals would differ between anatomists, pathologists and funeral workers, which reduces the likelihood that such exposures could explain the observed increases in risk.

Until recently, the findings for leukaemia in studies of professional workers appeared to be contradicted by the lack of such findings among industrial workers. However, some evidence for an excess of deaths from leukaemia has been reported in the recent updates of two of the three major cohort studies of industrial workers. A statistically significant exposure–response relationship was observed between peak exposures to formaldehyde and mortality from leukaemia in the study of industrial workers in the USA. This relationship was found to be particularly strong for myeloid leukaemia, a finding that was also observed in the study of anatomists and in several of the studies of embalmers. However, in the study of industrial workers in the USA, mortality from leukaemia was lower than expected when comparisons were made using the general population as the referent group. This raises concerns about whether these findings are robust with respect to the choice of a comparison group. Leukaemia has been found to be associated with socioeconomic status, and that of industrial workers tends to be low. Thus, the lack of an overall finding of an excess of deaths from leukaemia in the cohort of industrial workers in the USA might be explained by biases in the comparison between the study and referent populations. The study also failed to demonstrate an exposure–response relationship with cumulative exposure, although other metrics may sometimes be more relevant.

Mortality from leukaemia was also found to be in excess in the recent update of the study of garment workers exposed to formaldehyde in the USA. A small and statistically non-significant excess was observed for the entire cohort in comparison with rates among the general population. This excess was somewhat stronger for myeloid leukaemia, which is consistent with the findings from the study of industrial workers in the USA and several of the studies of medical professionals and embalmers. The excess was also stronger among workers who had a long duration of exposure and long follow-up, and who had been employed early in the study period when exposures to formaldehyde were believed to be highest. This pattern of findings is generally consistent with what might be expected if, in fact, exposure to formaldehyde were causally associated with a risk for leukaemia. The positive associations observed in many of the subgroup analyses presented in the study of garment workers in the USA were based on a relatively small number of deaths, and were thus not statistically stable.

The updated study of British industrial workers failed to demonstrate excess mortality among workers exposed to formaldehyde. The lack of positive findings in this study is difficult to reconcile with the findings from the studies of garment workers and industrial workers in the USA and studies of professionals. This was a high-quality study of adequate size and with sufficiently long follow-up to have had a reasonable chance to detect an excess of deaths from leukaemia. The British study did not include an evaluation of peak exposures, but neither did the study of garments workers in the USA nor the studies of professionals. Also, the British study did not examine specifically the risk for myeloid leukaemia, which represented the strongest findings in the studies of garment workers and industrial workers in the USA and in several of the studies of medical professionals and funeral workers.

In summary, there is strong but not sufficient evidence for a causal association between leukaemia and occupational exposure to formaldehyde. Increased risk for leukaemia has consistently been observed in studies of professional workers and in two of three of the most relevant studies of industrial workers. These findings fall slightly short of being fully persuasive because of some limitations in the findings from the cohorts of industrial and garment workers in the USA and because they conflict with the non-positive findings from the British cohort of industrial workers.