title: Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment.
abstract: In 2010, the World Health Organization (WHO) established an indoor air quality guideline for short- and long-term exposures to formaldehyde (FA) of 0.1 mg/m3(0.08 ppm) for all 30-min periods at lifelong exposure. This guideline was supported by studies from 2010 to 2013. Since 2013, new key studies have been published and key cancer cohorts have been updated, which we have evaluated and compared with the WHO guideline. FA is genotoxic, causing DNA adduct formation, and has a clastogenic effect; exposure-response relationships were nonlinear. Relevant genetic polymorphisms were not identified. Normal indoor air FA concentrations do not pass beyond the respiratory epithelium, and therefore FA's direct effects are limited to portal-of-entry effects. However, systemic effects have been observed in rats and mice, which may be due to secondary effects as airway inflammation and (sensory) irritation of eyes and the upper airways, which inter alia decreases respiratory ventilation. Both secondary effects are prevented at the guideline level. Nasopharyngeal cancer and leukaemia were observed inconsistently among studies; new updates of the US National Cancer Institute (NCI) cohort confirmed that the relative risk was not increased with mean FA exposures below 1 ppm and peak exposures below 4 ppm. Hodgkin's lymphoma, not observed in the other studies reviewed and not considered FA dependent, was increased in the NCI cohort at a mean concentration ≥0.6 mg/m3and at peak exposures ≥2.5 mg/m3; both levels are above the WHO guideline. Overall, the credibility of the WHO guideline has not been challenged by new studies.
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, 2100, Copenhagen, Denmark. gdn@nrcwe.dk.
authors.forename: Gunnar Damgård
authors.initials: GD
authors.lastname: Nielsen
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, 2100, Copenhagen, Denmark.
authors.forename: Søren Thor
authors.initials: ST
authors.lastname: Larsen
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, 2100, Copenhagen, Denmark.
authors.forename: Peder
authors.initials: P
authors.lastname: Wolkoff
mesh_terms: D000393:Air Pollutants / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D016902:Air Pollution, Indoor / Q000009:adverse effects / Q000517:prevention & control*; D000818:Animals; D002274:Carcinogens, Environmental / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D004202:Disinfectants / Q000032:analysis / Q000378:metabolism / Q000633:toxicity; D005557:Formaldehyde / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D014943:Global Health; D017408:Guidelines as Topic; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects / Q000517:prevention & control / Q000592:standards; D009153:Mutagens / Q000032:analysis / Q000378:metabolism / Q000633:toxicity; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D012142:Respiratory Tract Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D018570:Risk Assessment; D066007:Toxicokinetics; D014944:World Health Organization
chemical_list: D000393:Air Pollutants; D002274:Carcinogens, Environmental; D004202:Disinfectants; D009153:Mutagens; D005557:Formaldehyde
keywords: Cancer; Formaldehyde; Indoor air guideline; Risk assessment; World Health Organization