CHAPTER 29: Effect of In Vivo Formaldehyde Exposure on DNA Damage Measured by the Micronucleus Assay in Lymphocytes, Buccal, and Nasal Cells

Formaldehyde (FAL) is a Class I carcinogen. Occupational exposure to this chemical is not uncommon and 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, therefore, performed a systematic review and statistical analysis of the results from all published reports (N = 17 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 indicate that the majority (62%) of these studies showed significant increases in lymphocyte micronuclei (MN), a biomarker of chromosome breakage or loss, in exposed subjects relative to controls. The results of all studies (positive or negative), when pooled together, indicated a highly significant doubling in lymphocyte MN frequency in those exposed to FAL relative to controls (P < 0.0001). In similar studies using buccal cells (N = 7 studies) and nasal cells (N = 6 studies) the MN frequency was increased by a factor of 2.6 (P = 0.031) and 2.2 (P = 0.030), respectively, in those exposed to FAL relative to controls. These results are consistent with the World Health Organization (WHO) recommendation not to exceed exposure to 0.081 ppm, given that the means (range) of exposure concentrations were 0.74 (0.05–2.56) ppm, 0.77 (0.06–3.01) ppm, and 0.55 (0.09–1.40) ppm in the lymphocyte, buccal and nasal cell studies, respectively, and, therefore, they were mainly above the WHO safe limit. These observations indicate the suitability of MN assays to measure the in vivo genotoxicity of FAL.