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

Abstract

There is a relatively large body of research on the potential cardiovascular (CV) effects associated with short-term ozone exposure (defined by EPA as less than 30 days in duration). We conducted a weight-of-evidence (WoE) analysis to assess whether it supports a causal relationship using a novel WoE framework adapted from the US EPA's National Ambient Air Quality Standards causality framework. Specifically, we synthesized and critically evaluated the relevant epidemiology, controlled human exposure, and experimental animal data and made a causal determination using the same categories proposed by the Institute of Medicine report Improving the Presumptive Disability Decision-making Process for Veterans (). We found that the totality of the data indicates that the results for CV effects are largely null across human and experimental animal studies. The few statistically significant associations reported in epidemiology studies of CV morbidity and mortality are very small in magnitude and likely attributable to confounding, bias, or chance. In experimental animal studies, the reported statistically significant effects at high exposures are not observed at lower exposures and thus not likely relevant to current ambient ozone exposures in humans. The available data also do not support a biologically plausible mechanism for CV effects of ozone. Overall, the current WoE provides no convincing case for a causal relationship between short-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 short-term exposure to ozone and CV effects as “below equipoise.”

Keywords:

• acute toxicity
• air pollution
• cardiovascular system
• causal framework
• epidemiology
• mode of action
• risk assessment
• systematic review
• weight of evidence

Declaration of interest

The authors are employed by Gradient, a private environmental consulting firm, and Albany Medical College, a private medical school. Gradient staff have strong expertise in assessing human, experimental animal, and mechanistic data in WoE analyses (as is evident in recent evaluations conducted for bisphenol A, naphthalene, formaldehyde, chlorpyrifos, methanol, styrene, nickel, and toluene diisocyanate) and have presented several of these analyses to regulatory bodies. In addition, Gradient staff, including the authors of this paper, have carefully evaluated the science underlying EPA's review of various NAAQS and offered both oral and written testimony to EPA. Gradient has also addressed issues on systematic review and integration of evidence for a number of clients. The work reported in this paper was conducted by the authors during the normal course of employment with financial support provided by the American Petroleum Institute (API). API is the major trade association of corporations in the petroleum sector, from discovery through production and refining. While drafts of this paper were reviewed by members or affiliates of API, the authors have the sole responsibility for the writing, content, and conclusions in this paper. The conclusions are not necessarily those of API.