Weight of evidence for cross-species conservation of androgen receptor-based biological activity.

The U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP) is tasked with assessing chemicals for their potential to perturb endocrine pathways, including those controlled by androgen receptor (AR). To address challenges associated with traditional testing strategies, EDSP is considering in vitro high-throughput screening assays to screen and prioritize chemicals more efficiently. The ability of these assays to accurately reflect chemical interactions in nonmammalian species remains uncertain. Therefore, a goal of the EDSP is to evaluate how broadly results can be extrapolated across taxa. To assess the cross-species conservation of AR-modulated pathways, computational analyses and systematic literature review approaches were used to conduct a comprehensive analysis of existing in silico, in vitro, and in vivo data. First, molecular target conservation was assessed across 585 diverse species based on the structural similarity of ARs. These results indicate that ARs are conserved across vertebrates and are predicted to share similarly susceptibility to chemicals that interact with the human AR. Systematic analysis of over 5000 published manuscripts was used to compile in vitro and in vivo cross-species toxicity data. Assessment of in vitro data indicates conservation of responses occurs across vertebrate ARs, with potential differences in sensitivity. Similarly, in vivo data indicate strong conservation of the AR signaling pathways across vertebrate species, although sensitivity may vary. Overall, this study demonstrates a framework for utilizing bioinformatics and existing data to build weight of evidence for cross-species extrapolation and provides a technical basis for extrapolating hAR-based data to prioritize hazard in nonmammalian vertebrate species.

Differences in Fine Particle Exposure and Estimated Pulmonary Ventilation Rate with Respect to Work Tasks of Wildland Firefighters at Prescribed Burns: A Repeated Measures Study.

Wildland firefighters (WLFFs) are exposed to a mixture of chemicals found in wildland fire smoke and emissions from nonwildland-fuel smoke sources such as diesel. We investigated compositional differences in exposure to particulate matter and explored differences in ventilation rate and potential inhaled dose relative to the work tasks of WLFFs. Repeated measures on ten professional and two volunteer firefighters were collected on prescribed burn and nonburn days. Personal monitoring consisted of real-time and gravimetric fine particulate matter (PM2.5), carbon monoxide (CO), and accelerometer measurements to estimate ventilation rate and potential dose of PM2.5. The fine particulate matter was analyzed for levoglucosan (LG) and light absorbing carbon as a surrogate for black carbon (BC). Breathing zone personal exposure concentrations of PM2.5, LG, BC, and CO were higher on burn days (P < 0.05). Differences in exposure concentrations were observed between burn day tasks (P < 0.05) with firefighters managing fire boundaries (holders) being exposed to higher CO and LG concentrations and less BC concentrations than those conducting lighting (lighters). While no statistical difference in PM2.5 exposure measures was observed between the two tasks, holders in the study tended to be exposed to higher PM2.5 concentrations (~1.4×), while lighters tended to have more inhaled amounts of PM2.5 (~1.3×). Our findings demonstrate possible diversity in the sources of particulate matter exposure at the fireline and suggest the potential importance of using dose as a metric of inhalation exposure in occupational or other settings.

Impact of South Asian brick kiln emission mitigation strategies on select pollutants and near-term Arctic temperature responses.

The brick kiln industrial sector in South Asia accounts for large amounts of short-lived climate forcer (SLCF) emissions, namely black carbon (BC), organic carbon (OC), and sulfur dioxide (SO2; the precursor to atmospheric sulfate [SO4]). These SLCFs are air pollutants and have important impacts on both human health and the Arctic, a region currently experiencing more than double the rate of warming relative to the global average. Using previously derived Arctic equilibrium temperature response factors, we estimate the contribution to Arctic temperature impacts from previously reported emissions of BC, OC, and SO2 from four prevalent South Asian brick kiln types (Bull's Trench [BTK], Down Draught [DDK], Vertical Shaft [VSBK], and Zig-zag). Net annual BC (115 gigagrams [Gg]), OC (17 Gg), and SO2 (350 Gg) baseline emissions from all four South Asian kiln types resulted in 3.36 milliKelvin (mK) of Arctic surface warming. Given these baseline emissions and Arctic temperature responses, we estimate the current and maximum potential emission and temperature mitigation considering two kiln type conversions. Assuming no change in brick production, baseline emissions have been reduced by 17% when considering current BTK to Zig-zag conversions and have the potential to decrease by 82% given a 100% future conversion rate. This results in a 25% and 119% reduction in Arctic warming, respectively. Replacing DDKs with VSBKs increases baseline SLCF emissions by 28% based on current conversions and has the potential to increase by 131%. This conversion still reduces baseline warming by 31% and 149%, respectively. These results show that brick kiln conversions can have different impacts on local air quality and Arctic climate. When considering brick kiln emissions mitigation options, regional and/or local policy action should consider several factors, including local air quality, worker health and safety, cost, quality of bricks, as well as global climate impacts.

Estimating Arctic Temperature Impacts from Select European Residential Heating Appliances and Mitigation Strategies.

The use of residential heating devices is a key source of black carbon and other short-lived climate forcer emissions in Arctic and other high latitude regions, with important impacts to the Arctic climate and human health. The types of combustion technologies and fuels used varies by region, which impacts the emission profiles of these pollutants and thus the magnitude of Arctic climate responses. Using emission inventory data from 14 European countries, we derive wood-fueled residential heating emissions of black carbon, organic carbon, and sulfate from six appliance types in 2016. Using previously derived equilibrium Arctic temperature responses, we estimate Arctic temperature influences from each appliance type. Using the 2016 appliance emission data as a baseline, we compute the emission mass and Arctic temperature mitigation potential from hypothetical stove conversion scenarios. A total of 43.2 gigagrams (Gg) of black carbon, 175.7 Gg of organic carbon, and 10.3 Gg of sulfate were emitted in 2016 from the six appliance types in the 14 countries. The combined emissions increased Arctic surface temperatures by +2.8 millikelvin. If each country converted its appliance fleet to the technologically advanced pellet stoves and boilers, the combined black carbon, organic carbon, and sulfate emissions from heating appliances could be reduced by 94% and the Arctic temperature response reduced by 85%. The specific source and originating region of emissions are important factors in resolving the magnitude of their impacts. Improved country-level accounting of specific appliances and their emission characteristics can lead to a better understanding of potential mitigation options.

Evidence of compensation among waterpipe smokers using harm reduction components.

OBJECTIVES: We examined two waterpipe tobacco smoking components advertised to reduce harm to determine if they result in lower levels of biomarkers of acute exposure. METHODS: We conducted a crossover study of 34 experienced waterpipe smokers smoking a research-grade waterpipe in three configurations ad libitum in a controlled chamber: control (quick-light charcoal), electric (electric heating) and bubble diffuser (quick-light charcoal and bubble diffuser). We collected data on smoking topography, environmental carbon monoxide (CO), subjective effects, heart rate, plasma nicotine and exhaled CO and benzene. RESULTS: Smokers' mean plasma nicotine, heart rate, and exhaled benzene and CO boost were all significantly lower for electric compared with control. However, smokers puffed more intensely and took significantly more and larger volume puffs for a larger total puffing volume (2.0 times larger, p<0.0001) when smoking electric; machine yields indicate this was likely due to lower mainstream nicotine. Smokers rated electric smoking experience less satisfying and less pleasant. For charcoal heating, the mean mass of CO emitted into the chamber was ~1 g when participants smoked for a mean of 32 minutes at a typical residential ventilation rate (2.3 hr-1). CONCLUSION: Waterpipe smokers engaged in compensation (i.e., increased and more intense puffing) to make up for decreased mainstream nicotine delivery from the same tobacco heated two ways. Waterpipe components can affect human puffing behaviours, exposures and subjective effects. Evidence reported here supports regulation of waterpipe components, smoking bans in multifamily housing and the use of human studies to evaluate modified or reduced risk claims.

Measuring acute pulmonary responses to occupational wildland fire smoke exposure using exhaled breath condensate.

Wildland firefighters are directly exposed to elevated levels of wildland fire (WF) smoke. Although studies demonstrate WF smoke exposure is associated with lung function changes, few studies that use invasive sample collection methods have been conducted to investigate underlying biochemical changes. These methods are also either unrepresentative of the deeper airways or capable of inducing inflammation. In the present study, levels of biomarkers of oxidative stress (8-isoprostane) and pro-inflammatory response (interleukin-6 [IL-6], interleukin-8 [IL-8], C-reactive protein [CRP], and soluble intercellular adhesion molecule-1 [sICAM-1]) were determined in exhaled breath condensate (EBC) samples that were collected from firefighters before, after, and next morning following prescribed burn and regular work shifts. Results show only a marginal cross-shift increase in 8-isoprostane on burn days (.05 < p value < .1), suggesting WF smoke exposure causes mild pulmonary responses.

Urinary mutagenicity and other biomarkers of occupational smoke exposure of wildland firefighters and oxidative stress.

Background: Wildland firefighters conducting prescribed burns are exposed to a complex mixture of pollutants, requiring an integrated measure of exposure. Objective: We used urinary mutagenicity to assess if systemic exposure to mutagens is higher in firefighters after working at prescribed burns versus after non-burn work days. Other biomarkers of exposure and oxidative stress markers were also measured. Methods: Using a repeated measures study design, we collected urine before, immediately after, and the morning after a work shift on prescribed burn and non-burn work days from 12 healthy subjects, and analyzed for malondialdehyde (MDA), 8-isoprostane, 1-hydroxypyrene (OH-pyrene), and mutagenicity in Salmonella YG1041 +S9. Particulate matter (PM2.5) and carbon monoxide (CO) were measured by personal monitoring. Light-absorbing carbon (LAC) of PM2.5 was measured as a surrogate for black carbon exposure. Linear mixed-effect models were used to assess cross-work shift changes in urinary biomarkers. Results: No significant differences occurred in creatinine-adjusted urinary mutagenicity across the work shift between burn days and non-burn days. Firefighters lighting fires had a non-significant, 1.6-fold increase in urinary mutagenicity for burn versus non-burn day exposures. Positive associations were found between cross-work shift changes in creatinine-adjusted urinary mutagenicity and MDA (p = 0.0010), OH-pyrene (p = 0.0001), and mass absorption efficiency which is the LAC/PM2.5 ratio (p = 0.2245), respectively. No significant effect of day type or work task on cross-work shift changes in MDA or 8-isoprostane was observed. Conclusion: Urinary mutagenicity may serve as a suitable measure of occupational smoke exposures among wildland firefighters, especially among those lighting fires for prescribed burns.

Impact of Work Task-Related Acute Occupational Smoke Exposures on Select Proinflammatory Immune Parameters in Wildland Firefighters.

OBJECTIVE: A repeated measures study was used to assess the effect of work tasks on select proinflammatory biomarkers in firefighters working at prescribed burns. METHODS: Ten firefighters and two volunteers were monitored for particulate matter and carbon monoxide on workdays, January to July 2015. Before and after workshift dried blood spots were analyzed for inflammatory mediators using the Meso Scale Discovery assay, while blood smears were used to assess leukocyte parameters. RESULTS: Firefighters lighting with drip-torches had higher cross-work-shift increases in interleukin-8, C-reactive protein, and serum amyloid A compared with holding, a task involving management of fire boundaries. A positive association between interleukin-8 and segmented-neutrophil was observed. CONCLUSION: Results from this study suggest that intermittent occupational diesel exposures contribute to cross-work-shift changes in host systemic innate inflammation as indicated by elevated interleukin-8 levels and peripheral blood segmented-neutrophils.

Review of the health effects of wildland fire smoke on wildland firefighters and the public.

Each year, the general public and wildland firefighters in the US are exposed to smoke from wildland fires. As part of an effort to characterize health risks of breathing this smoke, a review of the literature was conducted using five major databases, including PubMed and MEDLINE Web of Knowledge, to identify smoke components that present the highest hazard potential, the mechanisms of toxicity, review epidemiological studies for health effects and identify the current gap in knowledge on the health impacts of wildland fire smoke exposure. Respiratory events measured in time series studies as incidences of disease-caused mortality, hospital admissions, emergency room visits and symptoms in asthma and chronic obstructive pulmonary disease patients are the health effects that are most commonly associated with community level exposure to wildland fire smoke. A few recent studies have also determined associations between acute wildland fire smoke exposure and cardiovascular health end-points. These cardiopulmonary effects were mostly observed in association with ambient air concentrations of fine particulate matter (PM2.5). However, research on the health effects of this mixture is currently limited. The health effects of acute exposures beyond susceptible populations and the effects of chronic exposures experienced by the wildland firefighter are largely unknown. Longitudinal studies of wildland firefighters during and/or after the firefighting career could help elucidate some of the unknown health impacts of cumulative exposure to wildland fire smoke, establish occupational exposure limits and help determine the types of exposure controls that may be applicable to the occupation.