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

Right heart pressure increases after acute increases in ambient particulate concentration.

OBJECTIVES: We explored the association between acute changes in daily mean pulmonary artery (PA) and right ventricular (RV) pressures and concentrations of ambient fine particulate matter [PM with aerodynamic diameter \u3c or = 2.5 microm (PM(2.5))] as an explanation for previous associations between congestive heart failure (HF) hospital admissions and PM. MATERIALS AND METHODS: In the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, to see whether management of ambulatory HF could be improved by providing continuous right heart pressure monitoring to physicians, the Chronicle Implantable Hemodynamic Monitor (Medtronic, Inc., Minneapolis, MN, USA) continuously measured multiple right heart hemodynamic parameters, heart rate, and activity trends in subjects with moderate/severe HF. Using these trial data, we calculated daily mean pressures, using only those time intervals where the subject was not physically active (n = 5,807 person-days; n = 11 subjects). We then studied the association between mean daily PA/RV pressures and mean ambient PM(2.5) concentrations on the same day and previous 6 days. RESULTS: Each 11.62-microg/m(3) increase in same-day mean PM(2.5) concentration was associated with small but significant increases in estimated PA diastolic pressure [0.19 mmHg; 95% confidence interval (CI), 0.05-0.33] and RV diastolic pressure (0.23 mmHg; 95% CI, 0.11-0.34). Although we saw considerable differences in the magnitude of response by COMPASS-HF randomization group (total data access for physicians vs. blocked clinician access), season, left ventricular ejection fraction, and obesity, these effects were not significantly different. CONCLUSIONS: These pilot study findings provide a potential mechanism for previous findings of increased risk of HF associated with ambient PM. However, because of the small number of subjects, a larger study is needed for confirmation