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

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

Population and distribution of beavers Castor fiber

1. A century ago, overhunting had reduced Eurasian beaver Castor fiber populations to c. 1200 animals in scattered refugia from France to Mongolia. Reintroductions and natural spread have since restored the species to large areas of its original range. Population has more than tripled since the first modern estimate in 1998; the minimum estimate is now c. 1.5 million. 2. Range expansion 2000–2020 has been rapid, with large extensions in western and south-central Europe, southern Russia, and west and central Siberia. Beavers are now re-established in all countries of their former European range except for Portugal, Italy, and the southern Balkans; they occur broadly across Siberia to Mongolia, with scattered populations father east. About half of the world population lives in Russia. Populations appear to be mature in much of European Russia, Belarus, the Baltic States, and Poland. 3. There is a significant population of North American beaver Castor canadensis in Finland and north-west Russia. Most other 20th-Century introductions of this species have become extinct or been removed. 4. Recent DNA studies have improved understanding of Castor fiber population prehistory and history. Two clades, east and west, are extant; a third ‘Danube’ clade is extinct. Refugial populations were strongly bottlenecked, with loss of genetic diversity through genetic drift. 5. Future range extension, and large increases in populations and in impacts on freshwater systems, can be expected. Beavers are now recolonising densely populated, intensely modified, low-relief regions, such as England, the Netherlands, Belgium, and north-west Germany. They will become much more common and widespread there in coming decades. As beavers are ecosystem engineers with profound effects on riparian habitats, attention to integrating beaver management into these landscapes using experience gained in other areas – before the rapid increase in population densities and impacts occurs – is recommended. beaver, Castor fiber, Castor canadensis, distribution, Eurasia, population, reintroductionpublishedVersio