Formaldehyde is widely used in the United States and other countries. Occupational and environmental exposures to
formaldehyde may be associated with an increased risk of
leukemia in exposed individuals. However, risk assessment of
formaldehyde and
leukemia has been challenging due to inconsistencies in human and animal studies and the lack of a known mechanism for
leukemia induction. Here, we provide a summary of the symposium at the Environmental
Mutagen Society Meeting in 2008, which focused on the epidemiology of
formaldehyde and
leukemia, potential mechanisms, and implication for risk assessment, with emphasis on future directions in multidisciplinary
formaldehyde research. Updated results of two of the three largest industrial cohort studies of
formaldehyde-exposed workers have shown positive associations with
leukemia, particularly
myeloid leukemia, and a recent meta-analysis of studies to date supports this association. Recent mechanistic studies have shown the formation of
formaldehyde-induced
DNA adducts and characterized the essential DNA repair pathways that mitigate
formaldehyde toxicity. The implications of the updated findings for the design of future studies to more effectively assess the risk of
leukemia arising from
formaldehyde exposure were discussed and specific recommendations were made. A toxicogenomic approach in experimental models and human exposure studies, together with the measurement of
biomarkers of internal exposure, such as
formaldehyde-
DNA and
protein adducts, should prove fruitful. It was recognized that increased communication among scientists who perform epidemiology, toxicology, biology, and risk assessment could enhance the design of future studies, which could ultimately reduce uncertainty in the risk assessment of
formaldehyde and
leukemia.