Researchers in the Occupational and Environmental Epidemiology Branch (OEEB) have been conducting studies of occupational formaldehyde exposure and cancer risk since the 1980s. Early studies focused on surveys of professionals who are potentially exposed to formaldehyde in their work, such as anatomists and embalmers (Walrath and Fraumeni 1983; Walrath and Fraumeni 1984; Stroup et al. 1986; Hayes et al. 1990). Although these early studies reported that these professionals were at increased risk for leukemia compared to the general population, they did not evaluate specific exposures or work practices. More recently, OEEB scientists conducted a study investigating the relationship between work practices and formaldehyde exposure with risk for selected malignancies among workers in the funeral industry. Occupational histories were obtained from next of kin and co-workers for cases of lymphohematopoietic malignancies (n=167) and for a control group of deaths due to other causes. Risk of death from myeloid (n=34) but not other types of leukemia, was increased among those whose peak exposure to formaldehyde was highest. There was also evidence that greater than average levels of exposure to formaldehyde in these jobs was related to risk of death from myeloid leukemia (Hauptmann et al. 2009).
In the NCI Formaldehyde Industrial Cohort study, which began in the 1980s and includes 25,619 workers in industries with potential formaldehyde exposure, OEEB scientists estimated exposure based on work histories and plant-specific measurement data. In the most recent publication from this cohort, which focused on deaths from lympohematopoietic malignancies, a possible link between formaldehyde exposure and lymphohematopoietic malignancies, particularly myeloid leukemia (n=48), was observed with peak exposure. When cumulative risk was evaluated, risks declined steadily over time, such that the cumulative excess risk of myeloid leukemia was no longer statistically significant at the end of the follow-up period. Similar to patterns of risk over time seen for known leukemogens, the risk for myeloid leukemia appeared to be highest earlier in the follow-up period. By the end of the follow-up period, the risk was no longer statistically significant (Beane Freeman et al. 2009). Also of note, formaldehyde exposure was associated with increased risk of death from nasopharyngeal cancer (Hauptmann et al. 2004).
Formaldehyde undergoes rapid chemical changes immediately after absorption into the body. Therefore, some scientists think that formaldehyde is unlikely to have effects at sites other than the upper respiratory tract. To determine if formaldehyde exposure may disrupt hematopoietic function and produce leukemia-related chromosome changes in exposed humans, OEEB investigators examined the ability of formaldehyde to disrupt hematopoiesis in a study of 43 workers exposed to formaldehyde and 51 frequency-matched controls by measuring complete blood counts and peripheral stem/progenitor cell colony formation. Myeloid progenitor cells, the target for leukemogenesis, were cultured from the workers to quantify the level of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in metaphase spreads of these cells. Among exposed workers, peripheral blood cell counts were significantly lowered in a manner consistent with toxic effects on the bone marrow and leukemia-specific chromosome changes were significantly elevated in myeloid blood progenitor cells. These findings suggest that formaldehyde exposure can have an adverse effect on the hematopoietic system and that leukemia induction by formaldehyde is biologically plausible (Zhang et al. 2010). These findings will require replication.
Results from these studies have been cited in several reviews on the carcinogenicity of formaldehyde including those conducted by the International Agency for Research on Cancer and the National Toxicology Program Report on Carcinogens Outside Expert Panel.
For more information, contact Laura Beane-Freeman.
NCI’s Fact Sheet on Formaldehyde and Cancer Risk http://www.cancer.gov/cancertopics/factsheet/Risk/formaldehyde