Abstract
Studies about formaldehyde (FA) published since the guideline of 0.1 mg/m(3) by the World Health Organization (WHO) in 2010 have been evaluated; critical effects were eye and nasal (portal-of-entry) irritation. Also, it was considered to prevent long-term effects, including all types of cancer. The majority of the recent toxicokinetic studies showed no exposure-dependent FA-DNA adducts outside the portal-of-entry area and FA-DNA adducts at distant sites were due to endogenously generated FA. The no-observed-adverse-effect level for sensory irritation was 0.5 ppm and recently reconfirmed in hypo- and hypersensitive individuals. Investigation of the relationship between FA exposure and asthma or other airway effects in children showed no convincing association. In rats, repeated exposures showed no point mutation in the p53 and K-Ras genes at ≤15 ppm neither increased cell proliferation, histopathological changes and changes in gene expression at 0.7 ppm. Repeated controlled exposures (0.5 ppm with peaks at 1 ppm) did not increase micronucleus formation in human buccal cells or nasal tissue (0.7 ppm) or in vivo genotoxicity in peripheral blood lymphocytes (0.7 ppm), but higher occupational exposures were associated with genotoxicity in buccal cells and cultivated peripheral blood lymphocytes. It is still valid that exposures not inducing nasal squamous cell carcinoma in rats will not induce nasopharyngeal cancer or lymphohematopoietic malignancies in humans. Reproductive and developmental toxicity are not considered relevant in the absence of sensory irritation. In conclusion, the WHO guideline has been strengthened.