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

The encrusting sponge Halisarca laxus: population genetics and association with the ascidian Pyura spinifera

Abstract The encrusting sponge Halisarca laxus forms a seemingly obligate association with the stalked solitary ascidian Pyura spinifera. In 1991 we examined spatial variation and short-term temporal variation in this association at three neighbouring sites in southeastern Australia. This sponge dominated the surface of almost all the 500 individual ascidians examined, with mean cover usually exceeding 90%. This pattern was consistent among sites and throughout the year of the study. The domination of a small isolated patch of habitable substratum by a sponge is most unusual, given that they are regarded as relatively poor recruiters. To understand how this association might be maintained, we determined the underlying genotypic diversity of the sponge population using starch-gel electrophoresis. P. spinifera is a clump-forming ascidian and usually occurs in clumps of up to 22 individuals. Electrophoretic surveys, based on six variable allozyme loci, revealed that at a total of five plots within three neighbouring New South Wales populations, single sponge genotypes may cover entire ascidian clumps; although a clump sometimes played host to more than one sponge clone. Allele frequencies (averaged across four loci that appear to conform to Mendelian inheritance) showed little variation among populations (standardised genetic variance, Fs~ = 0.013). Nevertheless, sponge populations were genotypically diverse, with samples from 63 of 172 individual clumps displaying unique "clonal" genotypes. Moreover, multi-locus genotypic diversity within all sites approached the level expected for sexual reproduction with random mating. Taken together, these data imply that H. laxus produces sexually-derived larvae that are at least moderately widely dispersed. Given the relatively small size of the patches that this sponge inhabits, we also conclude that these larvae are good colonists and good spatial competitors on their ascidian hosts.A. R. Davis, D. J. Ayre , M. R. Billingham, C. A. Styan, G. A. Whit