Is exposure to formaldehyde in air causally associated with leukemia?—A hypothesis-based weight-of-evidence analysis

Abstract

Recent scientific debate has focused on the potential for inhaled formaldehyde to cause lymphohematopoietic cancers, particularly leukemias, in humans. The concern stems from certain epidemiology studies reporting an association, although particulars of endpoints and dosimetry are inconsistent across studies and several other studies show no such effects. Animal studies generally report neither hematotoxicity nor leukemia associated with formaldehyde inhalation, and hematotoxicity studies in humans are inconsistent. Formaldehyde's reactivity has been thought to preclude systemic exposure following inhalation, and its apparent inability to reach and affect the target tissues attacked by known leukemogens has, heretofore, led to skepticism regarding its potential to cause human lymphohematopoietic cancers. Recently, however, potential modes of action for formaldehyde leukemogenesis have been hypothesized, and it has been suggested that formaldehyde be identified as a known human leukemogen. In this article, we apply our hypothesis-based weight-of-evidence (HBWoE) approach to evaluate the large body of evidence regarding formaldehyde and leukemogenesis, attending to how human, animal, and mode-of-action results inform one another. We trace the logic of inference within and across all studies, and articulate how one could account for the suite of available observations under the various proposed hypotheses. Upon comparison of alternative proposals regarding what causal processes may have led to the array of observations as we see them, we conclude that the case fora causal association is weak and strains biological plausibility. Instead, apparent association between formaldehyde inhalation and leukemia in some human studies is better interpreted as due to chance or confounding.

Epidemiology of Leukemia and Multiple Myeloma in Golestan, Iran

“…The ASRs of MM are higher in developed countries (male=3.3, female=2.2 per 100000 person-year) than less developed areas (male= 0.7, female=0.8 per 100000 person-year). Risk factors for leukemia are previous chemotherapy, genetic disorders caused by abnormal chromosomes, human T cell leukemia virus, myelodysplastic syndrome (Rhomberg et al, 2011). Age and race are considered as risk factors for multiple myeloma.…”

Richtwert für Formaldehyd in der Innenraumluft

“…Im aktuellen Follow-up der zweiten US-Studie hat sich der zunächst beobachtete Zusammenhang zwischen Formaldehyd-Exposition und Leukämie nicht bestätigt [27,28]. Insgesamt wird der Zusammenhang als gering erachtet und biologisch als nicht plausibel angesehen [29].…”

Systematic Reviews for Occupational Safety and Health Questions: Resources for Evidence Synthesis

“…Researchers have proposed more-formalized approaches to weight-of-evidence approaches, such as quantitative frameworks using multi-criteria decision-analysis methodology, incorporating decision-analysis tools, using hypothesis-based assessments to better communicate uncertainties and inconsistencies, applying quantitative structure-activity relationship modeling, performing sequential analyses of lines of evidence to rule out risks, or using discriminant analyses to assign empirically based weights (Hull and Swanson, 2006;Matthews et al, 2007;Hujoel, 2009;Swaen and Van Amelsvoort, 2009;Rhomberg, Bailey, and Goodman, 2010;Linkov et al, 2011;Rhomberg et al, 2011;Pemberton, Bailey, and Rhomberg, 2013;Prueitt, Rhomberg, and Goodman, 2013;Rorije et al, 2013;Jiang et al, 2015;and Linkov et al, 2015). Others have advocated paradigm shifts, such as the use of Bayesian methods to integrate evidence from reviewed research and prior knowledge (Linkov et al, 2015).…”