A systematic review of the association between occupational exposure to formaldehyde and effects on chromosomal DNA damage measured using the cytokinesis-block micronucleus assay in lymphocytes.

Formaldehyde (FAL) is classified as a Class I carcinogen by the WHO International Agency for Research on Cancer. Therefore, there is a need to validate appropriate methods for detecting its genotoxic effects in vivo in humans. One of the most commonly used methods to measure the genotoxic effects of exposure to environmental chemicals is the lymphocyte cytokinesis-block micronucleus (L-CBMN assay). We performed a systematic review and statistical analysis of the results from all of the published studies in which the L-CBMN assay was used to measure the genotoxic effects of human exposure to FAL. The results of this systematic review indicated that the majority (62%) of the 21 investigations in the 17 published studies we examined showed significant increases in lymphocyte micronucleus (MN) frequency (a biomarker of chromosome breakage or loss), in exposed subjects relative to controls. We used a novel quality score tool to determine if the investigations adequately addressed known variables that affect MN frequency in lymphocytes and found that MN frequency was not explained by quality because there was no significant correlation between quality score and fold-change in MN frequency (R=0.008, P=0.97). The results of all of the studies (positive or negative), when combined together, indicated a highly significant doubling in lymphocyte MN frequency in those exposed to FAL relative to controls (P<0.0001). These observations, together with a significant positive correlation between L-CBMN assay MN frequency and FAL air concentration (R=0.529, P=0.017) indicate the suitability of this method to measure in vivo genotoxicity of FAL. Furthermore, fold-increase in lymphocyte MN frequency in the exposed subjects relative to controls was strongly positively correlated with the duration of FAL exposure (R=0.779, P<0.0001) suggesting the need to better understand the potential for cumulative genomic instability induced by chronic exposures to FAL.