BACKGROUND:Current risk assessments of cardiovascular disease (CVD) outcomes attributable to transportation noise rely on estimates from the 2018 WHO Environmental Noise Guidelines. Since the publication of these guidelines, several studies have been conducted to determine the association between transportation noise sources and CVD; however, recent meta-analyses have not derived updated exposure-response functions. OBJECTIVE:We reviewed epidemiological evidence linking long-term exposure to road traffic, railway, and aircraft noise with non-fatal and fatal myocardial infarction, ischemic heart disease, stroke, and ischemic stroke, and derived exposure-response functions using the conventional and Burden of Proof (BoP) methodologies. METHODS:We systematically searched databases for cohort or case-control studies that determined the associations between non-fatal and/or fatal myocardial infarction, ischemic heart disease, stroke, and ischemic stroke and long-term exposure to road traffic, railway, aircraft noise in general populations. Exposure-response functions were generated using the conventional natural cubic splines and Burden of Proof Risk Function approaches. RESULTS:Twenty-six studies met our eligibility criteria. Road traffic noise was associated with 1% increase in the combined risk of stroke incidence and mortality (RR = 1.01, 95%CI: 1.00-1.02, p-value = 0.04), and with 5% increase under the BoP framework (RR = 1.05, 95%UI: 1.03-1.07). Railway noise was associated with 1% increase in myocardial infarction outcomes (RR = 1.01, 95%CI: 1.01-1.01, p-value < 0.0001), and with 16% increase under the BoP framework (RR = 1.16 95%UI: 1.07-1.26). Of the twelve risk-outcome pairs examined, five showed no evidence of association, four showed weak evidence, and the remainder lacked credible evidence or did not meet the BoP criteria. Compared with the natural splines approach, the BoP framework produced more plausible exposure-response curves. SIGNIFICANCE:This study adds to the existing literature by providing a comprehensive comparison of the association between long-term exposure to transportation noise sources and CVD outcomes using both conventional and BoP methodologies. IMPACT STATEMENT:This is the first study to apply the conventional meta-regression and Burden of Proof methodologies to systematically quantify and evaluate associations between long-term exposure to transportation noise sources (i.e., road traffic, railway, and aircraft) and combined risk of fatal and non-fatal cardiovascular disease outcomes, including myocardial infarction, ischemic heart disease, stroke, and ischemic stroke. The application of these two approaches to deriving exposure-response functions provides additional insights into the quantification of the burden of disease attributable to transportation noise. Our findings using the Burden of Proof framework on transportation noise and CVD outcomes advance the integration of an additional environmental risk factor and propose new risk-outcome pairs for potential inclusion in the Global Burden of Disease study.

Exposure to fine particles (PM2.5) has been associated with adverse health outcomes, even at low exposure levels (< 10 µg/m3). Burden of disease assessments can quantify these associations; however, their sensitivity to methodological choices limits comparability between studies. This study aimed to quantify the impact of methodological choices on disease burden attributable to low levels of ambient PM2.5, using Norway as a case study. Key methodological choices included (i) population exposure data, (ii) concentration-response curves, and (iii) population health data. Data from national and international sources were applied, including the global burden of disease (GBD) study. Attributable mortality and disability-adjusted life years (DALY) were estimated using burden of disease methodology. Additionally, the impact of choices related to concentration-response curves was assessed for higher exposure levels, using a scenario where exposure distributions were shifted to mean exposures up to 30 µg/m3. Methodological choices related to the concentration-response curves had the largest impacts on the estimated attributable deaths, ranging from − 91

AIMS:The Joint Action project on Cancer and other Non-communicable Diseases (NCDs) prevention, Action on Health Determinants, includes a dedicated workstream on structural and population-level interventions. The overarching objective of this workstream is to strengthen the compliance, coherence, implementation and enforcement of evidence-based regulatory measures that support governmental efforts to reduce the burden of NCDs. METHODS:The workstream adopts a multi-method approach, informed by existing academic literature and previous European studies. Key methodologies include policy mapping, evidence reviews, behavioural assessments, policy impact modelling, and pilot testing. Governmental alcohol and tobacco policies will be evaluated using comparative policy scales, while the health and economic impacts of health taxation policies will be projected through and microsimulation modelling. Nutrient profile modelling and food composition databases will be developed to inform strategies for food reformulation. The effectiveness of labelling interventions will be examined. Tools for monitoring digital marketing exposure will be developed, and the impact of environmental policy impact will be assessed. EXPECTED RESULTS:The workstream is expected to deliver comprehensive policy analyses, demonstrate the potential impact of health taxation, propose harmonized nutrient profiling frameworks, assess the effectiveness of food and alcohol labelling practices and contribute to the development of cross-national structures for public food procurement. Additionally, it will provide guidance on the implementation of effective measures and evaluate divergences in national policy approaches across Europe. CONCLUSIONS:The workstream will generate actionable evidence and documentation to inform and support public policy processes, thereby contributing to reductions in the burden of preventable disease across the region.

Multiple deprivation indices (MDIs) measure community-level deprivation using various socio-economic indicators such as education level, unemployment rate, or family structure. With their growing use across Europe and the need to evaluate health impacts on vulnerable populations, this scoping review provides an overview of MDIs in the region. Insights into their construction methods will help provide guidance to researchers in developing future indices. This scoping review was conducted as part of the four-year research project funded through EU Horizon Europe-Burden of disease-based methods for estimating the socio-economic cost of environmental stressors (BEST-COST). We searched Medline, Embase, and Web of Science using terms covering deprivation in Europe. Articles meeting the inclusion criteria were reviewed to identify MDIs and their methodologies. Those including a health indicator were excluded from the study. From 163 articles meeting our inclusion criteria, 18 MDIs were identified. The number of underlying indicators ranged from 4 to 22 across MDIs. Most indices were built for small geographical areas, such as municipalities, districts, or census tracts. Ten indices applied weights derived from statistical methods such as principal components analysis, while the other eight applied equal weights and calculated the index as a simple arithmetic sum or mean composite score. The review highlights high variability in MDI methodologies and emphasizes that aligning MDI selection with the context and objectives of a study. Furthermore, due to the vast cultural and geographical diversity across European countries, developing a Europe-wide index requires careful consideration of the methodologies to be employed.

Abstract Background Ambient air pollution and noise substantially impact public health and the economy. Different methods to quantify these impacts are described in the literature. Objectives Within the European project BEST-COST (Burden of disease-based methods for estimating the socio-economic cost of environmental stressors), we aim to develop an open-source R package to quantify and monetise the disease burden attributable to air pollution and noise, including the impact of social inequalities. Methods The developed code will allow for different calculation pathways including: single baseline health data vs. age-specific estimates from life tables; relative and absolute risk; scenario comparison based on the population attributable fraction vs. population impact fraction; single-pollutant vs. correlated exposures; and outdoor vs. indoor air pollution. Moreover, the package can digest a variety of input data formats for the exposure-response function (e.g. relative risk with fixed shape vs. user-defined function) and exposure data (e.g. population-weighted mean vs. categorical distribution, spatial data). Eligible impact metrics will include morbidity incidence and prevalence, number of deaths, years of life lost, and years lived with disability. Finally, the R package will enable quantifying social inequities (using a novel multiple deprivation index) and monetising the attributable disease burden (using a state-of-the-art approach). Results During development, the R package will be tested in BEST-COST case studies in 5 European countries (BE, EE, FR, NO, PT), compared with existing tools, and discussed with key users in a workshop. The final R package will be available on GitHub in 2026. Conclusions This tool will allow the quantification and monetisation of the health impact of air pollution and noise. The R package will be a flexible programming resource that can be used as a standalone or combined with existing tools to build a more solid basis for evidence-based policy making. Key messages • This open-source tool will allow the quantification and monetisation of the health impact of air pollution and noise, including the impact of social inequalities. • The R package will be a flexible programming resource that can be used as a standalone or combined with existing tools to build a more solid basis for evidence-based policy making.

Ortho-phthalates (herein referred to as phthalates) are synthetic chemicals used in thousands of different everyday products and materials. Nearly ubiquitous environmental exposure is reflected by phthalate metabolites in the urine of almost all Canadians. However, phthalate exposure tends to be higher amongst people of low socioeconomic status and ethnic minorities. Substantial evidence shows that certain phthalates cause harm to human health, particularly developing fetuses and children. Governments vary in their approach to assessing and managing risks associated with phthalates. Canada continues to take a more permissive stance on phthalate regulations compared to the EU and some US states. We argue that the recent Canadian national risk assessment on phthalates does not appropriately reflect the growing evidence demonstrating harm to human health from phthalate exposure and does not adequately consider the evidence showing higher exposures faced by vulnerable populations. Canadians would benefit from adopting a more stringent regulatory approach to phthalates. Specifically, Canada should expand phthalate restrictions to apply to all consumer products, implement sunset dates toward eliminating the use of existing phthalates, and mandate publicly available evidence of no harm for phthalate alternatives. Canadian alignment on phthalate regulations with the EU and a growing number of US states could encourage other countries to follow suit.

Recently, the causal associations between traffic emissions and health effects were strengthened by the systematic reviews by the Health Effects Institute (HEI#23, 2022). According to EuroStat data Europeans spend 87-97% of their time indoors in homes, workplaces, schools and nurseries. Breathing volumes are dominated by the time spent indoors (16 m³ indoors and 1.4 m³ outdoors), even though breathing rates in outdoor environments are higher. This demonstrates the importance of taking into account time activity as well as infiltration to indoor spaces when estimating intake of particles. The ULTRHAS project aims to link in vitro toxicological evidence for particulate matter to health impact assessments to look specifically into this. An integrated exposure pathway model will consider for different microenvironments, and physical activity patterns to quantify the particle intake in selected gender and age groups. Relative to the commonly applied approach using residential address and corresponding outdoor pollution levels we specifically add handling of (i) infiltration into indoor spaces and (ii) variability in breathing volumes based on physical activities. The model will provide inhalation volumes for selected target populations, to be applied in the intake-DALY estimation of burden of disease parameters in the following phases of the project.

Environmental noise is of considerable public health concern, and quantification of the health impacts is important for preventive strategies. In this project we estimated the burden of disease due to road traffic and railway noise in four Nordic countries and their capital cities in terms of DALYs (Disability-Adjusted Life Years). Available data on noise exposure were used, including data from strategic noise mapping according to the Environmental Noise Directive, END (Directive 2002/49/EC). High degree of noise annoyance (HA), high degree of sleep disturbance (HSD) and ischemic heart disease (IHD) were included in the analyses based on exposure-response associations recommended by WHO. Country-specific estimates of IHD from the Global Burden of Disease (GBD) study were used. Since several aspects of the noise exposure modelling vary considerably between the Nordic countries, no comparable estimates could be made for the entire countries. For the capital cities comparable estimates ranged from 330 to 485 DALYs/100,000 for road traffic noise, and from 40 to 140 DALYs/100 000 for railway noise. High annoyance and high degree of sleep disturbance accounted for the largest part of DALYs for road traffic and railway noise, respectively. Further harmonization of noise exposure modelling is important for comparative disease burden assessment.

Environmental noise is the second largest environmental risk factor in disease burden estimates for Europe. While socioeconomic inequalities in noise exposure have been reported, the impact of socioeconomic status (SES) on the disease burden attributable to noise exposure has to our knowledge not been reported previously. The aim of this study is to assess the impact of SES on traffic noise exposure and the associated disease burden in selected Nordic populations. We employed nationwide data on road traffic noise exposure and SES from Danish and Norwegian Nationwide Models. The impact of household income and education on traffic noise exposure was assessed using linear regression analyses. Burden of disease estimates were calculated for populations stratified according to their level of income and education in terms of Disability-Adjusted Life Years (DALY) for high degree of noise annoyance, high degree of sleep disturbance and ischaemic heart disease. The most consistent finding observed for the Danish population was that, compared to medium and low household income, high household income was associated with lower noise exposure. Moreover, the burden of disease estimates for high noise annoyance were up to 20% lower in the high compared to the lower household income groups.

Abstract Substantial social inequalities in almost all non-fatal and fatal health outcomes are one of the most consistent and universal epidemiological findings. Therefore, monitoring social inequalities in health is considered a key priority for researchers and policy makers. The Global Burden of Disease Injuries, and Risk Factors Study (GBD) is the most comprehensive worldwide observational epidemiological synthesis of data to date. However, currently, the GBD Study does not include the potential to stratify associated metrics, such as the disability-adjusted life years metric, by different socioeconomic factors, such as education or income level. Although The GBD Study does include the Socio-Demographic Index, this measure is only useful when comparing between, and not within, countries or regions. We conducted a Cox regression analysis using a national longitudinal prospective cohort study design and registry-based data linked at the individual-level. We stratified on educational groups and investigated cause-specific mortality rates over a 30-year period, adjusting for age, sex and 5-year age cohorts. We also calculate years of life lost (YLLs) stratified by educational groups, standardised by age, and presented for specific years - to investigate trends over time. We discuss the benefits and limitations of this “individual-level” stratification approach as one possible solution to the integration of social inequalities into the GBD study or when using a burden of disease framework approach more generally.

The Tobacco Products Directive (TPD) defines enhanced reporting obligations applying to 15 priority additives added to cigarettes and roll-your-own tobacco. A consortium of 12 international tobacco companies submitted 14 reports that were reviewed by an independent scientific body within the Joint Action on Tobacco Control (JATC). The reports were evaluated in accordance with the TPD with regard to their comprehensiveness, methodology and conclusions. Here we present their significant identified methodological limitations. The toxicological and chemical evaluation in the industry reports was mainly based on comparative testing, which lacks discriminative power for products with high toxicity and variability, like cigarettes. The literature reviews were biased, the comparative chemical studies did not assess previously identified pyrolysis products, the toxicological evaluation did not include the assessment of inhalation toxicity, and pyrolysis products were not assessed in terms of toxicity, including their genotoxic and carcinogenic potential. For both chemistry and toxicity testing, the statistical approach applied to test the difference between test and additive-free control cigarettes resulted in a high chance of false negatives. The clinical study for inhalation facilitation and nicotine uptake had limitations concerning study design and statistical analysis, while addictiveness was not assessed. Finally, the methodology used to assess characterizing flavors was flawed. In conclusion, there are significant limitations in the methodology applied by the industry. Therefore, the provided reports are of insufficient quality and are clearly not suitable to decide whether a priority additive should be banned in tobacco products according to the TPD.

The European Union Tobacco Products Directive (EU TPD) mandates enhanced reporting obligations for tobacco manufacturers regarding 15 priority additives. Within the Joint Action on Tobacco Control (JATC), a review panel of independent experts was appointed for the scientific evaluation of the additive reports submitted by a consortium of 12 tobacco manufacturers. As required by the TPD, the reports were evaluated based on their comprehensiveness, methodology and conclusions. In addition, we evaluated the chemical, toxicological, addictive, inhalation facilitating and flavoring properties of the priority additives based on the submitted reports, supplemented by the panel's expert knowledge and some independent literature. The industry concluded that none of the additives is associated with concern. Due to significant methodological limitations, we question the scientific validity of these conclusions and conclude that they are not warranted. Our review demonstrates that many issues regarding toxicity, addictiveness and attractiveness of the additives have not been sufficiently addressed, and therefore concerns remain. For example, menthol facilitates inhalation by activation of the cooling receptor TRPM8. The addition of sorbitol and guar gum leads to a significant increase of aldehydes that may contribute to toxicity and addictiveness. Titanium dioxide particles (aerodynamic diameter <10 µm) are legally classified as carcinogenic when inhaled. For diacetyl no report was provided. Overall, the industry reports were not comprehensive, and the information presented provides an insufficient basis for the regulation of most additives. We, therefore, advise MS to consider alternative approaches such as the precautionary principle.

Background Geographical differences in health outcomes are reported in many countries. Norway has led an active policy aiming for regional balance since the 1970s. Using data from the Global Burden of Disease Study (GBD) 2019, we examined regional differences in development and current state of health across Norwegian counties. Methods Data for life expectancy, healthy life expectancy (HALE), years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) in Norway and its 11 counties from 1990 to 2019 were extracted from GBD 2019. County-specific contributors to changes in life expectancy were compared. Inequality in disease burden was examined by use of the Gini coefficient. Findings Life expectancy and HALE improved in all Norwegian counties from 1990 to 2019. Improvements in life expectancy and HALE were greatest in the two counties with the lowest values in 1990: Oslo, in which life expectancy and HALE increased from 71.9 years (95% uncertainty interval 71.4-72.4) and 63.0 years (60.5-65.4) in 1990 to 81.3 years (80.0-82.7) and 70.6 years (67.4-73.6) in 2019, respectively; and Troms og Finnmark, in which life expectancy and HALE increased from 71.9 years (71.5-72.4) and 63.5 years (60.9-65.6) in 1990 to 80.3 years (79.4-81.2) and 70.0 years (66.8-72.2) in 2019, respectively. Increased life expectancy was mainly due to reductions in cardiovascular disease, neoplasms, and respiratory infections. No significant differences between the national YLD or DALY rates and the corresponding age-standardised rates were reported in any of the counties in 2019; however, Troms og Finnmark had a higher age-standardised YLL rate than the national rate (8394 per 100 000 [95% UI 7801-8944] vs 7536 per 100 000 [7391-7691]). Low inequality between counties was shown for life expectancy, HALE, all level-1 causes of DALYs, and exposure to level-1 risk factors. Interpretation Over the past 30 years, Norway has reduced inequality in disease burden between counties. However, inequalities still exist at a within-county level and along other sociodemographic gradients. Because of insufficient Norwegian primary data, there remains substantial uncertainty associated with regional estimates for non-fatal disease burden and exposure to risk factors. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

Phthalates are ubiquitous environmental contaminants associated with allergic disease in epidemiological and animal studies. This investigation aims to support these associations by interrogating systemic immune effects in allergen-sensitized volunteers after controlled indoor air exposure to a known concentration of dibutyl phthalate (DBP). The phthalate-allergen immune response (PAIR) study enrolled 16 allergen-sensitized participants to a double-blinded, randomized, crossover exposure to two conditions (DBP or control air for 3 hr), each followed immediately by inhaled allergen challenge. Peripheral blood immune cell composition and activation along with inflammatory mediators were measured before and after exposure. DBP exposure prior to the inhaled allergen challenge increased the percentage of CD4+ T helper cells and decreased the percentage of regulatory T cells (3 hr and 20 hr post-exposure), while only modest overall effects were observed for inflammatory mediators. The cells and mediators affected by the phthalate exposure were generally not overlapping with the endpoints affected by allergen inhalation alone. Thus, in distinction to our previously published effects on lung function, DBP appears to alter endpoints in peripheral blood that are not necessarily enhanced by allergen alone. Further studies are needed to clarify the role of phthalate-induced systemic effects in disease pathogenesis.

Abstract Background Single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptor gamma (PPAR-γ; gene: PPARG) and oxidative stress genes are associated with asthma risk. However, whether such variants modulate responses to dibutyl phthalate (DBP), a common plasticizer associated with increased asthma development, remains unknown. The purpose of this study is to investigate how SNPs in PPARG and oxidative stress genes, as represented by two separate genetic risk scores, modify the impact of DBP exposure on lung function and the airway and systemic response after an inhaled allergen challenge. Methods We conducted a double-blinded human crossover study with sixteen allergen-sensitized participants exposed for three hours to DBP and control air on distinct occasions separated by a 4-week washout. Each exposure was followed by an allergen inhalation challenge; subsequently, lung function was measured, and blood and bronchoalveolar lavage (BAL) were collected and analyzed for cell counts and allergen-specific immunoglobulin E (IgE). Genetic risk scores for PPAR-γ (P-GRS; weighted sum of PPARG SNPs rs10865710, rs709158, and rs3856806) and oxidative stress (OS-GRS; unweighted sum of 16 SNPs across multiple genes) were developed, and their ability to modify DBP effects were assessed using linear mixed-effects models. Results P-GRS and OS-GRS modified DBP effects on allergen-specific IgE in blood at 20 h (interaction effect [95% CI]: 1.43 [1.13 to 1.80], p = 0.005) and 3 h (0.99 [0.98 to 1], p = 0.03), respectively. P-GRS also modified DBP effects on Th2 cells in blood at 3 h (− 25.2 [− 47.7 to − 2.70], p = 0.03) and 20 h (− 39.1 [− 57.9 to − 20.3], p = 0.0005), and Th2 cells in BAL at 24 h (− 4.99 [− 8.97 to − 1.01], p = 0.02). An increasing P-GRS associated with reduced DBP effect on Th2 cells. Neither GRS significantly modified DBP effects on lung function parameters. Conclusions PPAR-γ variants modulated several airway and systemic immune responses to the ubiquitous chemical plasticizer DBP. Our results suggest that PPAR-γ variants may play a greater role than those in oxidative stress-related genes in airway allergic responses to DBP. Trial registration: This study reports results from The Phthalate-Allergen Immune Response Study that was registered on ClinicalTrials.gov with identification NCT02688478.

Biological sex influences disease severity, prevalence and response to therapy in allergic asthma. However, allergen-mediated sex-specific changes in lung protein biomarkers remain undefined. Here, we report sex-related differences in specific proteins secreted in the lungs of both mice and humans, in response to inhaled allergens. Female and male BALB/c mice (7-8 weeks) were intranasally challenged with the allergen house dust mite (HDM) for 2 weeks. Bronchoalveolar lavage fluid (BALF) was collected 24 hour after the last HDM challenge from allergen-naïve and HDM-challenged mice (N=10 per group, each sex). In a human study, adult participants were exposed to nebulized (2 min) allergens (based on individual sensitivity), BALF was obtained after 24 hour (N=5 each female and male). The BALF samples were examined in immunoblots for the abundance of 10 proteins shown to increase in response to allergen in both murine and human BALF, selected from proteomics studies. We showed significant sex-bias in allergen-driven increase in five out of the 10 selected proteins. Of these, increase in eosinophil peroxidase (EPX) was significantly higher in females compared to males, in both mice and human BALF. We also showed specific sex-related differences between murine and human samples. For example, allergen-driven increase in S100A8 and S100A9 was significantly higher in BALF of females compared to males in mice, but significantly higher in males compared to females in humans. Overall, this study provides sex-specific protein biomarkers that are enhanced in response to allergen in murine and human lungs, informing and motivating translational research in allergic asthma.

Abstract Background In addition to information on mortality and morbidity from diseases and injuries, it is important to identify the attributable burden of risk factors to allow for health planning and prioritization. Methods For the whole EU and each country, using estimates and 95% uncertainty intervals from the GBD 2019 study, we report attributable (all-cause and by level 2 risk factors) age-standardized death and DALY rates, as well as summary exposure values (SEV). We evaluate trends by comparing estimates for the year 2019 with those for the year 2010. Results Age-standardized death and DALY rates attributable to risk factors declined by 10.7% (95%UI 13.8%-7.6%) and 9.1% (95%UI 12.0%-6.3%), between 2010 and 2019 in the EU. While there was a decreasing trend for both age-standardized death and DALY rates for almost all risk factors, some showed an increasing trend on SEV, including low physical activity and intimate partner violence. Conclusions Despite the improvement of health metrics attributable to risk factors, several modifiable behavioral and metabolic risk factors remain unchanged over the years. It is crucial to ensure a swift implementation of evidence-based policies and interventions in EU member states to achieve the targets of the Sustainable Development Goals.

Background: Phthalate exposure has been associated with immune-related diseases such as asthma and allergies, but there is limited knowledge on mechanisms, effect biomarkers and thus biological support of causality. Objectives: To investigate associations between exposure to the phthalates DEHP (di(2-ethylhexyl) phthalate) and DiNP (diisononyl phthalate) and functional immune cell profiles. Methods: Peripheral blood mononuclear cells (PBMCs) from 32 healthy adult Norwegian participants in the EuroMix biomonitoring study were selected based on high or low (n = 16) levels of urine metabolites of DEHP and DiNP. High-dimensional immune cell profiling including phenotyping and functional markers was performed by mass cytometry (CyTOF) using two broad antibody panels after PMA/ionomycin-stimulation. The CITRUS algorithm with unsupervised clustering was used to identify group differences in cell subsets and expression of functional markers, verified by manual gating. Results: The group of participants with high phthalate exposure had a higher proportion of some particular innate immune cells, including CD11c positive NK-cell and intermediate monocyte subpopulations. The percentage of IFN gamma TNF alpha double positive NK cells and CD11b expression in other NK cell subsets were higher in the high exposure group. Among adaptive immune cells, however, the percentage of IL-6 and TNF alpha expressing naive B cell subpopulations and the percentage of particular naive cytotoxic T cell populations were lower in the high exposure group. Discussion: Cell subset percentages and expression of functional markers suggest that DEHP and DiNP phthalate exposure may stimulate subsets of innate immune cells and suppress adaptive immune cell subsets. By revealing significant immunological differences even in small groups, this study illustrates the promise of the broad and deep information obtained by high-dimensional single cell analyses of human samples to answer toxicological questions regarding health effects of environmental exposures.