Weight-of-evidence evaluation of long-term ozone exposure and cardiovascular effects

Crit Rev Toxicol. 2014 Oct;44(9):791-822. doi: 10.3109/10408444.2014.937855.

Abstract

We conducted a weight-of-evidence (WoE) analysis to assess whether the current body of research supports a causal relationship between long-term ozone exposure (defined by EPA as at least 30 days in duration) at ambient levels and cardiovascular (CV) effects. We used a novel WoE framework based on the United States Environmental Protection Agency's National Ambient Air Quality Standards causal framework for this analysis. Specifically, we critically evaluated and integrated the relevant epidemiology and experimental animal data and classified a causal determination based on categories proposed by the Institute of Medicine's 2008 report, Improving the Presumptive Disability Decision-making Process for Veterans. We found that the risks of CV effects are largely null across human and experimental animal studies. The few positive associations reported in studies of CV morbidity and mortality are very small in magnitude, mainly reported in single-pollutant models, and likely attributable to bias, chance, or confounding. The few positive effects in experimental animal studies were observed mainly in ex vivo studies at high exposures, and even the in vivo findings are not likely relevant to humans. The available data also do not support a biologically plausible mechanism for the effects of ozone on the CV system. Overall, the current WoE provides no convincing case for a causal relationship between long-term exposure to ambient ozone and adverse effects on the CV system in humans, but the limitations of the available studies preclude definitive conclusions regarding a lack of causation; thus, we categorize the strength of evidence for a causal relationship between long-term exposure to ozone and CV effects as "below equipoise."

Keywords: air pollution; cardiovascular system; causal framework; epidemiology; mode of action; risk assessment; systematic review; weight of evidence.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Air Pollutants
  • Air Pollution / adverse effects
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology
  • Environmental Exposure / adverse effects
  • Humans
  • Ozone / adverse effects*
  • Risk Assessment / methods
  • Toxicity Tests, Chronic

Substances

  • Air Pollutants
  • Ozone