A high throughput screening assay for human Thyroperoxidase inhibitors.

Rapid, human relevant assays are needed to assess potential hazards of the many chemicals in commerce. An assay of thyroid peroxidase (TPO) inhibition, using the substrate Amplex Ultra Red, was recently adapted for human TPO (AUR-hTPO). We tested a large number (788) of chemicals through this AUR-hTPO assay and compared performance with published results from an assay using enzyme from rat thyroid microsomes (AUR-rTPO).

Cumulative Health Risk from Exposure Load (CHREL): Looking at multi-chemical exposures through the lens of biomonitoring guidance values.

Exposure load (EL) is an indicator of multiple chemical exposures based on human biomonitoring data. We used EL methodology and human biomonitoring health-based guidance values (HB2GVs) as exposure thresholds to create a new metric called Cumulative Health Risk from Exposure Load (CHREL). HB2GVs are derived by calculating the concentration of a biomarker consistent with a health protective exposure guidance value.

Associations between paediatric obesity, chemical mixtures and environmental factors, in a national cross-sectional study of Canadian children.

Background: Whilst single chemical exposures are suspected to be obesogenic, the combined role of chemical mixtures in paediatric obesity is not well understood.

Objectives: We aimed to evaluate the potential associations between chemical mixtures and obesity in a population-based sample of Canadian children.

Methods: We ascertained biomonitoring and health data for children aged 3-11 from the cross-sectional Canadian Health Measures Survey from 2007 to 2019.

Harmonizing the assessment of allostatic load across cycles of the Canadian Health Measures Survey: Variable selection and calculation method.

Background: The availability of measures to operationalize allostatic load - the cumulative toll on the body of responding to stressor demands - in population health surveys may differ across years or surveys, hampering analyses on the entire sampled population. Here, impacts of variable selection and calculation method were evaluated to generate an allostatic load index applicable across all cycles of the Canadian Health Measures Survey (CHMS).

Methods: Data from CHMS cycles 1 to 4 were used to compare allostatic load scores when replacing the most prevalent risk factor, waist-to-hip ratio - available in cycles 1 to 4 but not 5 and 6 - with body mass index (BMI), waist circumference, waist circumference within BMI groups (classified as normal, overweight, or obese), or waist-to-height ratio.

Concordance between In Vitro and In Vivo Relative Toxic Potencies of Diesel Exhaust Particles from Different Biodiesel Blends.

Diesel exhaust particles (DEPs) contribute to air pollution exposure-related adverse health impacts. Here, we examined in vitro, and in vivo toxicities of DEPs from a Caterpillar C11 heavy-duty diesel engine emissions using ultra-low-sulfur diesel (ULSD) and biodiesel blends (20% /) of canola (B20C), soy (B20S), or tallow-waste fry oil (B20T) in ULSD. The in vitro effects of DEPs (DEP, DEP, DEP, and DEP) in exposed mouse monocyte/macrophage cells (J774A.

Modulation of insulin signaling pathway genes by ozone inhalation and the role of glucocorticoids: A multi-tissue analysis.

Air pollution is associated with increased risk of metabolic diseases including type 2 diabetes, of which dysregulation of the insulin-signaling pathway is a feature. While studies suggest pollutant exposure alters insulin signaling in certain tissues, there is a lack of comparison across multiple tissues needed for a holistic assessment of metabolic effects, and underlying mechanisms remain unclear. Air pollution increases plasma levels of glucocorticoids, systemic regulators of metabolic function.

Randomized Cross-Over Study of In-Vehicle Cabin Air Filtration, Air Pollution Exposure, and Acute Changes to Heart Rate Variability, Saliva Cortisol, and Cognitive Function.

To determine how traffic-related air pollution (TRAP) exposures affect commuter health, and whether cabin air filtration (CAF) can mitigate exposures, we conducted a cross-over study of 48 adults exposed to TRAP during two commutes with and without CAF. Measurements included particulate air pollutants (PM, black carbon [BC], ultrafine particles [UFPs]), volatile organic compounds, and nitrogen dioxide. We measured participants' heart rate variability (HRV), saliva cortisol, and cognitive function.

Hair cortisol as a viable tool for the assessment of an association between environmental noise exposure and chronic stress.

Entrenched in the well-established link between stress and health, noise exposure as a potential contributor to stress-related health effects receives tremendous attention. Indeed, exposure to noise can act as a stressor as evidenced through increased heart rate, blood pressure, adrenaline, epinephrine, and cortisol. Cortisol is secreted from the adrenal glands in response to stressor-induced activation of the hypothalamic-pituitary-adrenal axis.

Establishing an air-liquid interface exposure system for exposure of lung cells to gases.

Objective: Growing interest in non-animal-based models has led to the development of devices to expose cells to airborne substances. Cells/tissues grown at the air-liquid interface (ALI) are more representative of lung cells/tissues compared to submerged cell cultures. Additionally, airborne exposures should allow for closer modeling of human lung toxicity.

Acute cardiovascular effects of inhaled ambient particulate matter: Chemical composition-related oxidative stress, endothelin-1, blood pressure, and ST-segment changes in Wistar rats.

Short-term increases in particulate matter (PM) are associated with heightened morbidity and mortality from cardiovascular causes. Inhalation of PM is known to increase endothelin (ET)-1 levels. Yet, less is known about particle composition-related changes at the molecular level including the endothelinergic system and relationship with cardiovascular function changes.

Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity.

Exposure to air pollutants increases levels of circulating glucocorticoid stress hormones that exert profound effects relevant to health and disease. However, the nature and magnitude of tissue-level effects are modulated by factors that regulate local glucocorticoid activity; accordingly, inter-individual differences could contribute to susceptibility. In the present study, we characterized effects of ozone (O) inhalation on glucocorticoid-regulating factors in the lungs of rat strains with contrasting hypothalamic-pituitary-adrenal stress axis responses.

Sex-difference in air pollution-related acute circulatory and respiratory mortality and hospitalization.

Background: Numerous studies have estimated adverse effects of short-term exposure to ambient air pollution on public health. Few have focused on sex-differences, and results have been inconsistent. The purpose of this study was three-fold: to identify sex-differences in air pollution-related health outcomes; to examine sex-differences by cause and season; and to examine time trends in sex-differences.

Ozone-dependent increases in lung glucocorticoids and macrophage response: Effect modification by innate stress axis function.

Although considerable inter-individual variability exists in health effects associated with air pollutant exposure, underlying reasons remain unclear. We examined whether innate differences in stress axis function modify lung glucocorticoid and macrophage responses to ozone (O). Highly-stress responsive Fischer (F344) and less responsive Lewis (LEW) rats were exposed for 4 h by nose-only inhalation to air or O (0.

Exposure Load: Using biomonitoring data to quantify multi-chemical exposure burden in a population.

People are often concurrently exposed to numerous chemicals. Here we sought to leverage existing large biomonitoring datasets to improve our understanding of multi-chemical exposures in a population. Using nationally-representative data from the 2012-2015 Canadian Health Measures Survey (CHMS), we developed Exposure Load, a metric that counts the number of chemicals measured in people above a defined concentration threshold.

Air pollution exposure during pregnancy and childhood and brain morphology in preadolescents.

Background: Studies investigating the relationship between exposure to air pollution and brain development using magnetic resonance images are emerging. However, most studies have focused only on prenatal exposures, and have included a limited selection of pollutants. Here, we aim to expand the current knowledge by studying pregnancy and childhood exposure to a wide selection of pollutants, and brain morphology in preadolescents.

Residential greenness and indicators of stress and mental well-being in a Canadian national-level survey.

Background: Residential proximity to greenness in urban areas has been shown to confer a number of health benefits, including improved mental health. We investigated whether greenness was associated with self-reported stress, distress, and mental health among adult participants of multiple cycles of a national Canadian health survey, and whether these associations varied by sex, age, income, and neighbourhood characteristics.

Methods: Our study population included 397,900 participants of the Canadian Community Health Survey, 18 years of age or older, who lived in census metropolitan areas between 2000 and 2015.

Self-rated stress, distress, mental health, and health as modifiers of the association between long-term exposure to ambient pollutants and mortality.

Background: Individual and neighbourhood-scale socioeconomic characteristics modify associations between exposure to air pollution and mortality. The role of stress, which may integrate effects of social and environmental exposures on health, is unknown. We examined whether an individual's perspective on their own well-being, as assessed using self-rated measures of stress and health, modifies the pollutant-mortality relationship.

The association between ambient air pollution concentrations and psychological distress.

Background: A growing number of epidemiological studies have linked air pollution exposure to psychological conditions. Laboratory studies indicate that air pollutants can activate the neuroendocrine stress axis and modulate stress hormone levels, which could contribute to the development or exacerbation of psychological distress. The present study examined the spatial associations between air pollutants (fine particulate matter [PM], nitrogen dioxide [NO] and ground-level ozone [O]) and psychological distress among subjects in the most populous provinces in Canada.

Ozone increases plasma kynurenine-tryptophan ratio and impacts hippocampal serotonin receptor and neurotrophic factor expression: Role of stress hormones.

Air pollution is associated with adverse impacts on the brain, including cognitive decline and increased incidence of dementia, depression and anxiety; however, underlying mechanisms remain unclear. We have shown that both ozone and particulate matter activate the hypothalamic-pituitary-adrenal (HPA) axis, increasing plasma glucocorticoids and altering mRNA profiles in multiple tissues including the brain. HPA axis dysregulation has been associated with central nervous system impacts, including key effects in the hippocampus; accordingly, we hypothesized that pollutant-dependent increases in glucocorticoid levels impact biological pathways relevant to brain health.

Association of urinary polycyclic aromatic hydrocarbons and obesity in children aged 3-18: Canadian Health Measures Survey 2009-2015.

Polycyclic aromatic hydrocarbons (PAHs) may contribute to obesity. Childhood obesity is a strong predictor of adult obesity and morbidity; however, the relationship between PAHs and obesity in young children (e.g.

Effect of industrial point-source air pollutants on fractional exhaled nitric oxide in healthy volunteers.

Background: Few studies have examined the effects of industrial, fixed-site sources of air pollution on lung inflammation in nearby residents. We investigated the effects of short-term exposure to ambient air near a steel plant on the fractional exhaled concentration of nitric oxide (FeNO), a measure of airway inflammation, in healthy volunteers.

Methods: A cross-over study design was used.

Cumulative toll of exposure to stressors in Canadians: An allostatic load profile.

Background: The cumulative toll of exposure to stressors (psychosocial, chemical, physical) can contribute to disease processes. The concept of allostatic load, essentially the cost of maintaining physiological stability in response to environmental demands, may be useful in assessing broad population health impacts of stressors beyond morbidity and mortality. In the present study, allostatic load scores were generated for Canadians and associations with age, sex, education and household income were examined.

Air Pollution, Stress, and Allostatic Load: Linking Systemic and Central Nervous System Impacts.

Air pollution is a risk factor for cardiovascular and respiratory morbidity and mortality. A growing literature also links exposure to diverse air pollutants (e.g.