Framework for assessing causality of air pollution-related health effects for reviews of the National Ambient Air Quality Standards.

To inform regulatory decisions on the risk due to exposure to ambient air pollution, consistent and transparent communication of the scientific evidence is essential. The United States Environmental Protection Agency (U.S. EPA) develops the Integrated Science Assessment (ISA), which contains evaluations of the policy-relevant science on the effects of criteria air pollutants and conveys critical science judgments to inform decisions on the National Ambient Air Quality Standards. This article discusses the approach and causal framework used in the ISAs to evaluate and integrate various lines of scientific evidence and draw conclusions about the causal nature of air pollution-induced health effects. The framework has been applied to diverse pollutants and cancer and noncancer effects. To demonstrate its flexibility, we provide examples of causality judgments on relationships between health effects and pollutant exposures, drawing from recent ISAs for ozone, lead, carbon monoxide, and oxides of nitrogen. U.S. EPA's causal framework has increased transparency by establishing a structured process for evaluating and integrating various lines of evidence and uniform approach for determining causality. The framework brings consistency and specificity to the conclusions in the ISA, and the flexibility of the framework makes it relevant for evaluations of evidence across media and health effects.

Cross-species coherence in effects and modes of action in support of causality determinations in the U.S. Environmental Protection Agency's Integrated Science Assessment for Lead.

The peer-reviewed literature on the health and ecological effects of lead (Pb) indicates common effects and underlying modes of action across multiple organisms for several endpoints. Based on such observations, the United States (U.S.) Environmental Protection Agency (EPA) applied a cross-species approach in the 2013 Integrated Science Assessment (ISA) for Lead for evaluating the causality of relationships between Pb exposure and specific endpoints that are shared by humans, laboratory animals, and ecological receptors (i.e., hematological effects, reproductive and developmental effects, and nervous system effects). Other effects of Pb (i.e., cardiovascular, renal, and inflammatory responses) are less commonly assessed in aquatic and terrestrial wildlife limiting the application of cross-species comparisons. Determinations of causality in ISAs are guided by a framework for classifying the weight of evidence across scientific disciplines and across related effects by considering aspects such as biological plausibility and coherence. As illustrated for effects of Pb where evidence across species exists, the integration of coherent effects and common underlying modes of action can serve as a means to substantiate conclusions regarding the causal nature of the health and ecological effects of environmental toxicants.

Systematic review of the effects of black carbon on cardiovascular disease among individuals with pre-existing disease.

OBJECTIVES: Recent interest has developed in understanding the health effects attributable to different components of particulate matter. This review evaluates the effects of black carbon (BC) on cardiovascular disease in individuals with pre-existing disease using evidence from epidemiologic and experimental studies. METHODS: A systematic literature search was conducted to identify epidemiologic and experimental studies examining the relationship between BC and cardiovascular health effects in humans with pre-existing diseases. Nineteen epidemiologic and six experimental studies were included. Risk of bias was evaluated for each study. RESULTS: Evidence across studies suggested ambient BC is associated with changes in subclinical cardiovascular health effects in individuals with diabetes and coronary artery disease (CAD). Limited evidence demonstrated that chronic respiratory disease does not modify the effect of BC on cardiovascular health. CONCLUSIONS: Results in these studies consistently demonstrated that diabetes is a risk factor for BC-related cardiovascular effects, including increased interleukin-6 and ECG parameters. Cardiovascular effects were associated with BC in individuals with CAD, but few comparisons to individuals without CAD were provided in the literature.

Endogenous carbon monoxide production in disease.

Carbon monoxide (CO) in tissues and cells can originate from inhalation of CO or endogenously. Endogenous production, carboxyhemoglobin (COHb) formation, and exhaled CO levels are influenced by physiological factors, including disease. It is suggested that endogenous CO production can be used as a biomarker for oxidative and inflammatory processes. Also, endogenous CO can contribute to increased body burden of CO, which may both disrupt normal CO signaling cascades and increase the risk of CO toxicity.

Flavonoids protect against intercellular adhesion molecule-1 induction by benzo[a]pyrene.

Dietary changes are an attractive means of protecting against environmental chemical exposure. Exposure to benzo[a]pyrene (B[a]P) is a risk factor for cardiovascular disease events. It has recently been shown that B[a]P can increase intercellular adhesion molecule-1 (ICAM-1) in endothelial cells, a possible means of promoting cardiovascular disease. This study investigated the ability of flavonoids to protect against B[a]P-induced ICAM-1. It was shown that only flavonoids that contain a 4' B-ring hydroxyl substitution and a 2-3 C-ring double bond were protective. These data suggest that selected bioactive compounds can decrease proinflammatory properties of environmental chemicals such as B[a]P.