A cross-disciplinary evaluation of evidence for multipollutant effects on cardiovascular disease.

BACKGROUND: The current single-pollutant approach to regulating ambient air pollutants is effective at protecting public health, but efficiencies may be gained by addressing issues in a multipollutant context since multiple pollutants often have common sources and individuals are exposed to more than one pollutant at a time. OBJECTIVE: We performed a cross-disciplinary review of the effects of multipollutant exposures on cardiovascular effects. METHODS: A broad literature search for references including at least two criteria air pollutants (particulate matter [PM], ozone [O3], oxides of nitrogen, sulfur oxides, carbon monoxide) was conducted. References were culled based on scientific discipline then searched for terms related to cardiovascular disease. Most multipollutant epidemiologic and experimental (i.e., controlled human exposure, animal toxicology) studies examined PM and O3 together. DISCUSSION: Epidemiologic and experimental studies provide some evidence for O3 concentration modifying the effect of PM, although PM did not modify O3 risk estimates. Experimental studies of combined exposure to PM and O3 provided evidence for additivity, synergism, and/or antagonism depending on the specific health endpoint. Evidence for other pollutant pairs was more limited. CONCLUSIONS: Overall, the evidence for multipollutant effects was often heterogeneous, and the limited number of studies inhibited making a conclusion about the nature of the relationship between pollutant combinations and cardiovascular disease.

Using In Vitro High-Throughput Screening Data for Predicting Benzo[k]Fluoranthene Human Health Hazards.

Today there are more than 80,000 chemicals in commerce and the environment. The potential human health risks are unknown for the vast majority of these chemicals as they lack human health risk assessments, toxicity reference values, and risk screening values. We aim to use computational toxicology and quantitative high-throughput screening (qHTS) technologies to fill these data gaps, and begin to prioritize these chemicals for additional assessment. In this pilot, we demonstrate how we were able to identify that benzo[k]fluoranthene may induce DNA damage and steatosis using qHTS data and two separate adverse outcome pathways (AOPs). We also demonstrate how bootstrap natural spline-based meta-regression can be used to integrate data across multiple assay replicates to generate a concentration-response curve. We used this analysis to calculate an in vitro point of departure of 0.751 µM and risk-specific in vitro concentrations of 0.29 µM and 0.28 µM for 1:1,000 and 1:10,000 risk, respectively, for DNA damage. Based on the available evidence, and considering that only a single HSD17B4 assay is available, we have low overall confidence in the steatosis hazard identification. This case study suggests that coupling qHTS assays with AOPs and ontologies will facilitate hazard identification. Combining this with quantitative evidence integration methods, such as bootstrap meta-regression, may allow risk assessors to identify points of departure and risk-specific internal/in vitro concentrations. These results are sufficient to prioritize the chemicals; however, in the longer term we will need to estimate external doses for risk screening purposes, such as through margin of exposure methods.

What do the data show? Knowledge map development for comprehensive environmental assessment.

Environmental and human health risk assessments benefit from using data that cross multiple scientific domains. Although individual data points may often be readily understood, the total picture can be difficult to envision. This is especially true with gaps in the data (e.g., with emerging substances such as engineered nanomaterials [ENM]), such that simply presenting only known information can result in a skewed picture. This study describes a method for building knowledge maps (KM) to visually summarize factors relevant to risk assessment in a relatively easy to interpret format. The KMs were created in the context of the comprehensive environmental assessment (CEA) approach for research planning and risk management of environmental contaminants. Recent applications of CEA to emerging substances such as engineered nanomaterials that have numerous data gaps have suggested that a more visually based depiction of information would improve the approach. We developed KM templates as a pilot project, to represent pertinent aspects of conceptual domains, and to highlight gaps in available information for one particular portion of a specific CEA application: the comparison of environmental transport, transformation, and fate of multiwalled carbon nanotubes (MWCNTs) and decabromodiphenyl ether as flame retardants. The results are 3 KM templates representing Physical Properties, Transport, and Transformation. The 3 templates were applied to both substances, resulting in a total of 6 KMs. In addition to presenting the KMs, this paper details the process used to generate them, to aid KM development for other sections of CEA applied to MWCNTs, or to apply the process to new CEA applications.