The association between histopathologic effects and liver weight changes induced in mice and rats by chemical exposures: an analysis of the data from Toxicity Reference Database (ToxRefDB).

Absolute (ALW) and relative (RLW) liver weight changes are sensitive endpoints in repeat-dose rodent toxicity studies, and their changes are often used for quantitative assessment of health effects induced by hepatotoxic chemicals using the benchmark dose-response modeling (BMD) approach. To find biologically relevant liver weight changes to chemical exposures, we evaluated all data available for liver weight changes and associated liver histopathologic findings from the Toxicity Reference Database (ToxRefDB). Our analysis of 389 subchronic mouse and rat studies for 273 chemicals found significant differences in treatment-related ALW and RLW changes between dose groups with and without liver histopathologic changes. In addition, we demonstrate that chemical treatment-induced ALW and RLW changes can predict the presence of histopathologic findings and inform the selection of biologically relevant liver weight changes for BMD modeling and derivation of toxicity values.

Trends in Fire Danger and Population Exposure along the Wildland-Urban Interface.

The increased risk of wildfires and associated smoke exposure in the United States is a growing public health problem, particularly along the Wildland-Urban Interface (WUI). Using the measure of fire danger, the Energy Release Component, we define fire danger as the onset and duration of fire season, in the continental US, between 1979 and 2016. We then combine the measure of fire danger with census data to quantify changes in population fire exposure across the WUI. We determined that the largest increases in fire danger were observed in the Southwest, Intermountain, and Pacific Southwest regions. The increased fire danger, specifically during peak fire season, accounted for 6.1 more fires each year and 78,000 more acres burned each year, underscoring the link between fire danger and the risks of large fire occurrence and burn acreage. Finally, we observed significant population growth (121.2% between 1990 and 2010) within high-danger WUI areas, further implying significant increases in potential fire exposure.

Exploration of PM mass, source, and component-related factors that might explain heterogeneity in daily PM2.5-mortality associations across the United States.

Multi-city epidemiologic studies examining short-term (daily) differences in fine particulate matter (PM2.5) provide evidence of substantial spatial heterogeneity in city-specific mortality risk estimates across the United States. Because PM2.5 is a mixture of particles, both directly emitted from sources or formed through atmospheric reactions, some of this heterogeneity may be due to regional variations in PM2.5 toxicity. Using inverse variance weighted linear regression, we examined change in percent change in mortality in association with 24 "exposure" determinants representing three basic groupings based on potential explanations for differences in PM toxicity - size, source, and composition. Percent changes in mortality for the PM2.5-mortality association for 313 core-based statistical areas and their metropolitan divisions over 1999-2005 were used as the outcome. Several determinants were identified as potential contributors to heterogeneity: all mass fraction determinants, vehicle miles traveled (VMT) for diesel total, VMT gas per capita, PM2.5 ammonium, PM2.5 nitrate, and PM2.5 sulfate. In multivariable models, only daily correlation of PM2.5 with PM10 and long-term average PM2.5 mass concentration were retained, explaining approximately 10% of total variability. The results of this analysis contribute to the growing body of literature specifically focusing on assessing the underlying basis of the observed spatial heterogeneity in PM2.5-mortality effect estimates, continuing to demonstrate that this heterogeneity is multifactorial and not attributable to a single aspect of PM.

Annual PM2.5 and cardiovascular mortality rate data: Trends modified by county socioeconomic status in 2,132 US counties.

This article contains data on county-level socioeconomic status for 2132 US counties and each county's average annual cardiovascular mortality rate (CMR) and fine particulate matter (PM2.5) concentration for 21 years (1990-2010). County CMR, PM2.5, and socioeconomic data were obtained from the US National Center for Health Statistics, US Environmental Protection Agency's Community Multiscale Air Quality modeling system, and the US Census, respectively. Annual socioeconomic indices were created using seven county-level measures from the 1990, 2000, and 2010 US Census using factor analysis. Quintiles of this index were used to generate categories of county socioeconomic status. This national data set contains data for annual PM2.5 and CMR changes over a time-period when there was a significant reduction in US air pollutants (following the enactment of the 1970 Clean Air Act). These data are associated with the article "The contribution of improved air quality to reduced cardiovascular mortality: Declines in socioeconomic differences over time" [1]. Data are stored in a comma separated value format and can be downloaded from the USEPA ScienceHub data repository (https://doi.org/10.23719/1506014).

Impact of Reductions in Emissions from Major Source Sectors on Fine Particulate Matter-Related Cardiovascular Mortality.

BACKGROUND: Reductions in ambient concentrations of fine particulate matter (PM2.5) have contributed to reductions in cardiovascular (CV) mortality. OBJECTIVES: We examined changes in CV mortality attributed to reductions in emissions from mobile, point, areal, and nonroad sources through changes in concentrations of PM2.5 and its major components [nitrates, sulfates, elemental carbon (EC), and organic carbon (OC)] in 2,132 U.S. counties between 1990 and 2010. METHODS: Using Community Multiscale Air Quality model estimated PM2.5 total and component concentrations, we calculated population-weighted annual averages for each county. We estimated PM2.5 total- and component-related CV mortality, adjusted for county-level population characteristics and baseline PM2.5 concentrations. Using the index of Emission Mitigation Efficiency for primary emission-to-particle pathways, we expressed changes in particle-related mortality in terms of precursor emissions by each sector. RESULTS: PM2.5 reductions represented 5.7% of the overall decline in CV mortality. Large point source emissions of sulfur dioxide accounted for 6.685 [95% confidence interval (CI): 5.703, 7.667] fewer sulfate-related CV deaths per 100,000 people. Mobile source emissions of primary EC and nitrous oxides accounted for 3.396 (95% CI: 2.772, 4.020) and 3.984 (95% CI: 2.472, 5.496) fewer CV deaths per 100,000 people respectively. Increased EC and OC emissions from areal sources increased carbon-related CV mortality by 0.788 (95% CI: -0.540, 2.116) and 0.245 (95% CI: -0.697, 1.187) CV deaths per 100,000 people. DISCUSSION: In a nationwide epidemiological study of emission sector contribution to PM2.5-related mortality, we found that reductions in sulfur-dioxide emissions from large point sources and nitrates and EC emissions from mobile sources contributed the largest reduction in particle-related mortality rates respectively. https://doi.org/10.1289/EHP5692.