Does ambient air pollution influence biochemical markers of liver injury? Findings of a cross-sectional population-based survey.

BACKGROUND: There is limited evidence supporting an adverse effect of ambient air pollution on the liver. OBJECTIVES: To test the association between exposure to residential air pollution and serum biochemical indicators of liver injury. METHODS: We used a nationally representative sample of 32,989 participants aged 3-79 years old who participated in the Canadian Health Measures Survey between 2007 and 2019. Cross-sectional associations were assessed by generalized linear mixed models incorporating survey-specific sampling weights. RESULTS: The joint effect of an interquartile range (IQR) increase in nitrogen dioxide (NO2), ozone (O3) and fine particulate matter (PM2.5) was positively and significantly associated with all measures of liver injury adjusting for age, sex, education, income, smoking, alcohol consumption, body mass index (BMI), total cholesterol, diabetes, hypertension, and physical activity. The ranking of effect sizes from largest to smallest percent increases were 8.72% (95% confidence interval [CI] 7.56, 9.88) for alanine aminotransferase (ALT), 5.54% (95%CI 3.31, 7.77) for gamma-glutamyl transferase (GGT), 4.81% (95%CI 3.87, 5.74) for aspartate aminotransferase (AST), 2.46% (95%CI 0.26, 4.65) for total bilirubin (TBIL) and 1.18% (95%CI 0.62, 1.75) for alkaline phosphatase (ALP). Findings were not significantly different when stratified by age (≤16, >16 yr), sex, smoking (current, other), cholesterol (≤6.18, >6.18 mmol/l) and BMI (<30, ≥30 kg/m2). DISCUSSION: These findings suggest that ambient air pollution may have a relatively small impact on the liver, but these changes may have significant impact from a population health perspective, considering the ubiquitous nature of air pollution, or for individuals exposed to very high levels of air pollution.

Future temperature-related excess mortality under climate change and population aging scenarios in Canada.

OBJECTIVE: Climate change is expected to increase global temperatures. How temperature-related mortality risk will change is not completely understood, and how future demographic changes will affect temperature-related mortality needs to be clarified. We evaluate temperature-related mortality across Canada until 2099, accounting for age groups and scenarios of population growth. METHODS: We used daily counts of non-accidental mortality for 2000 to 2015 for all 111 health regions across Canada, incorporating in the study both urban and rural areas. A two-part time series analysis was used to estimate associations between mean daily temperatures and mortality. First, current and future daily mean temperature time series simulations were developed from Coupled Model Inter-Comparison Project 6 (CMIP6) climate model ensembles from past and projected climate change scenarios under Shared Socioeconomic Pathways (SSPs). Next, excess mortality due to heat and cold and the net difference were projected to 2099, also accounting for different regional and population aging scenarios. RESULTS: For 2000 to 2015, we identified 3,343,311 non-accidental deaths. On average, a net increase of 17.31% (95% eCI: 13.99, 20.62) in temperature-related excess mortality under a higher greenhouse gas emission scenario is expected for Canada in 2090-2099, which represents a greater burden than a scenario that assumed strong levels of greenhouse gas mitigation policies (net increase of 3.29%; 95% eCI: 1.41, 5.17). The highest net increase was observed among people aged 65 and over, and the largest increases in both net and heat- and cold-related mortality were observed in population scenarios that incorporated the highest rates of aging. CONCLUSION: Canada may expect net increases in temperature-related mortality under a higher emissions climate change scenario, compared to one assuming sustainable development. Urgent action is needed to mitigate future climate change impacts.

RéSUMé: OBJECTIF: Les changements climatiques devraient accroître les températures mondiales. La façon dont le risque de mortalité lié à la température évoluera n'est pas entièrement comprise, et la façon dont les changements démographiques futurs influeront sur la mortalité liée à la température doit être clarifiée. Nous étudions la mortalité liée à la température au Canada jusqu'en 2099, en tenant compte des groupes d'âge et des scénarios de croissance démographique. MéTHODES: Nous avons utilisé les nombres quotidiens de mortalité non accidentelle pour 2000 à 2015 pour toutes les 111 régions socio sanitaires du Canada, en intégrant dans l'étude des régions urbaines et rurales. Une analyse en séries chronologiques en deux parties a été utilisée pour estimer les associations entre les températures quotidiennes moyennes et la mortalité. Premièrement, des simulations de séries chronologiques de températures moyennes quotidiennes actuelles et futures ont été élaborées à partir d'ensembles de modèles climatiques du Projet de comparaison croisée 6 (CMIP6) du modèle couplé à partir de scénarios de changements climatiques passés et projetés dans le cadre de voies socioéconomiques partagées (SSP). Ensuite, la surmortalité due à la chaleur et au froid et la différence nette ont été projetées jusqu'en 2099, ce qui tient également compte de différents scénarios régionaux et de vieillissement de la population. RéSULTATS: De 2000 à 2015, nous avons recensé 3 343 311 décès non accidentels. En moyenne, une augmentation nette de 17,31% (eCI à 95%: 13,99, 20,62) de la mortalité excessive liée à la température dans le cadre d'un scénario d'émissions de gaz à effet de serre plus élevées est prévue pour le Canada en 2090­2099, ce qui représente un fardeau plus lourd qu'un scénario qui suppose des niveaux élevés de politiques d'atténuation des émissions de gaz (augmentation nette de 3,29%; eCI à 95%: 1,41, 5,17). La plus forte augmentation nette a été observée chez les personnes de 65 ans ou plus, et les plus fortes augmentations de la mortalité nette, de mortalité liée à la chaleur et au froid ont été observées dans les scénarios de population qui comprenaient les taux de vieillissement les plus élevés. CONCLUSION: Le Canada pourrait s'attendre à des augmentations nettes de la mortalité liée à la température dans le cadre d'un scénario de changement climatique à émissions plus élevées, comparativement à un scénario de développement durable. Des mesures urgentes sont nécessaires pour atténuer les répercussions futures des changements climatiques.

Do blood metals influence lipid profiles? Findings of a cross-sectional population-based survey.

Dyslipidemia, an imbalance of lipids and a major risk factor for cardiovascular disease, has been associated with elevated blood and urine levels of several heavy metals. Using data from a Canadian Health Measures Survey (CHMS), we tested associations between blood levels of cadmium, copper, mercury, lead, manganese, molybdenum, nickel, selenium, and zinc, and the lipids triglycerides (TG), total cholesterol (TC), low density lipoproteins (LDL), high density lipoproteins (HDL) and apolipoproteins A1 (APO A1), and B (APO B). All adjusted associations between single metals and lipids were positive and significant, except for APO A1 and HDL. The joint effect of an interquartile range increase in heavy metals was positively associated with percentage increases of TC, LDL and APO B of 8.82% (95%CI: 7.06, 10.57), 7.01% (95%CI: 2.51, 11.51) and 7.15% (95%CI: 0.51, 13.78), respectively. Future studies are warranted to determine if reducing environmental exposure to heavy metals favorably influences lipid profiles and the risk of cardiovascular disease.

Activity-related dyspnea in older adults participating in the Canadian Longitudinal Study on Aging.

BACKGROUND: Dyspnea is associated with functional impairment and impaired quality of life. There is limited information on the potential risk factors for dyspnea in an older adult population. OBJECTIVES: Among older adults aged 45 to 85 years of age, what sociodemographic, environmental, and disease related factors are correlated with dyspnea? DESIGN: We used cross-sectional questionnaire data collected on 28,854 participants of the Canadian Longitudinal Study of Aging (CLSA). Multinomial regression was used to assess the independent effect of individual variables adjusting for the other variables of interest. KEY RESULTS: The adjusted odds ratios for dyspnea "walking on flat surfaces" were highest for obesity (OR, 5.71; 95%CI, 4.71-6.93), lung disease (OR, 3.91; 95%CI, 3.41-4.49), and depression (OR, 3.68; 95%CI, 3.15-4.29), and were greater than 2 for lower income, and heart disease. The effect of diabetes remained significant after adjusting for sociodemographics, heart disease and BMI (OR, 1.61; 95%CI, 1.39-1.86). Those with both respiratory disease and depression had a 12.78-fold (95%CI, 10.09-16.19) increased odds of exertional dyspnea, while the corresponding OR for the combination of heart disease and depression was 18.31 (95%CI, 13.4-25.01). CONCLUSIONS: In a community sample of older adults, many correlates of dyspnea exist which have significant independent and combined effects. These factors should be considered in the clinical context where dyspnea is out of proportion to the degree of heart and lung disease. Whether or not diabetes may possibly be a risk factor for dyspnea merits further investigation.

The association between blood PFAS concentrations and clinical biochemical measures of organ function and metabolism in participants of the Canadian Health Measures Survey (CHMS).

Per- and poly-fluoroalkyl substances (PFAS) are ubiquitous and may persist in human tissue for several years. Only a small proportion of PFAS have been studied for human health effects. We tested the association between human blood levels of six PFAS and several clinical measures of organ and metabolic function in a nationally representative sample of 6768 participants aged 3-79 years old who participated in the Canadian Health Measures Survey. Cross-sectional associations were assessed by generalized linear mixed models incorporating survey-specific sampling weights. An increase in perfluorooctanoic acid (PFOA) equivalent to the magnitude of its geometric mean (GM) of 2.0 µg/L was associated with percentage (95% CI) increases in serum enzymes reflecting liver function: aspartate aminotransferase (AST) 3.7 (1.1, 6.4), gamma-glutamyl transferase (GGT) 11.8 (2.5, 21.8), alanine aminotransferase (ALT) 3.2 (0.5, 5.9), and bilirubin 3.6 (2.7, 4.5). A GM increase in perfluorodecanoic acid (PFDA) of 0.2 µg/L was positively associated with percentage increases in GGT, triglycerides, low-density lipoprotein (LDL) cholesterol, total cholesterol, and calcium with respective increases of 15.5 (2.2, 30.4), 7.0 (1.0, 13.2), 10.7 (5.5, 16.1), 2.8 (0.2, 5.3), and 0.8 (0.3, 1.3). PFOA, perfluorooctane sulfonate (PFOS), PFDA and perfluorononanoic acid (PFNA) were positively associated with GGT. All six congeners were positively associated with at least one biomarker of lipid metabolism, and 5 of 6, PFOA, PFOS, PFDA, perfluorohexane sulfonate (PFHxS) and PFNA were positively associated with serum calcium. Exposure to selected PFAS is associated with clinical blood tests reflecting metabolism and the function of several organ systems. These relatively small changes may possibly indicate early pathology that is clinically inapparent and may possibly be of significance in a general population or in individuals exposed to very high levels of PFAS.

Long-term ozone exposure and mortality from neurological diseases in Canada.

BACKGROUND: There is increasing interest in the health effects of air pollution. However, the relationships between ozone exposure and mortality attributable to neurological diseases remain unclear. OBJECTIVES: To assess associations of long-term exposure to ozone with death from Parkinson's disease, dementia, stroke, and multiple sclerosis. METHODS: Our analyses were based on the 2001 Canadian Census Health and Environment Cohort. Census participants were linked with vital statistics records through 2016, resulting in a cohort of 3.5 million adults/51,045,700 person-years, with 8,500/51,300/43,300/1,300 deaths from Parkinson's/dementia/stroke/multiple sclerosis, respectively. Ten-year average ozone concentrations estimated by chemical transport models and adjusted by ground measurements were assigned to subjects based on postal codes. Cox proportional hazards models were used to calculate hazard ratios (HRs) for deaths from the four neurological diseases, adjusting for eight common demographic and socioeconomic factors, seven environmental indexes, and six contextual covariates. RESULTS: The fully adjusted HRs for Parkinson's, dementia, stroke, and multiple sclerosis mortalities related to one interquartile range increase in ozone (10.1 ppb), were 1.09 (95% confidence interval 1.04-1.14), 1.08 (1.06-1.10), 1.06 (1.04-1.09), and 1.35 (1.20-1.51), respectively. The covariates did not influence significance of the ozone-mortality associations, except airshed (i.e., broad region of Canada). During the period of 2001-2016, 5.66%/5.01%/ 3.77%/19.11% of deaths from Parkinson's/dementia/stroke/multiple sclerosis, respectively, were attributable to ozone exposure. CONCLUSIONS: We found positive associations between ozone exposure and mortality due to Parkinson's, dementia, stroke, and multiple sclerosis.

The association between air pollution and COVID-19 related mortality in Santiago, Chile: A daily time series analysis.

BACKGROUND: Exposure to ambient air pollution is a risk factor for morbidity and mortality from lung and heart disease. RESEARCH QUESTION: Does short term exposure to ambient air pollution influence COVID-19 related mortality? STUDY DESIGN AND METHODOLOGY: Using time series analyses we tested the association between daily changes in air pollution measured by stationary monitors in and around Santiago, Chile and deaths from laboratory confirmed or suspected COVID-19 between March 16 and August 31, 2020. Results were adjusted for temporal trends, temperature and humidity, and stratified by age and sex. RESULTS: There were 10,069 COVID-19 related deaths of which 7659 were laboratory confirmed. Using distributed lags, the cumulative relative risk (RR) (95% CI) of mortality for an interquartile range (IQR) increase in CO, NO2 and PM2.5 were 1.061 (1.033-1.089), 1.067 (1.023-1.103) and 1.058 (1.034-1.082), respectively There were no significant differences in RR by sex.. In those at least 85 years old, an IQR increase in NO2 was associated with a 12.7% (95% CI 4.2-22.2) increase in daily mortality. CONCLUSION: This study provides evidence that daily increases in air pollution increase the risk of dying from COVID-19, especially in the elderly.

The influence of demographic and lifestyle factors on urinary levels of PAH metabolites-empirical analyses of Cycle 2 (2009-2011) CHMS data.

Polycyclic aromatic hydrocarbons (PAHs) are a group of compounds formed during the incomplete combustion of organic matter. Several are mutagenic carcinogens; the magnitude of exposure can be assessed by examining urinary levels of PAH metabolites. Data from biomonitoring studies that record urinary PAH metabolite levels, as well as demographic and lifestyle information, can be used to investigate relationships between PAH exposure and variables, such as smoking status, workplace smoking restrictions, age, sex, household income, home age, and occupation. This study analysed creatinine-adjusted urinary PAH metabolite concentrations and questionnaire data from ~1200 individuals aged 16 years and older surveyed in Cycle 2 of the Canadian Health Measures Survey (CHMS). Statistical analyses revealed that smoking status, age, and sex are associated with urinary concentrations of a pyrene metabolite (1-OHP), phenanthrene metabolites (ΣOH-Phen), fluorene metabolites (ΣOH-Flu) and naphthalene metabolites (ΣOH-Nap). More specifically, smoking status, age and sex can collectively account for 30, 24, 52, and 34% of the observed variations in 1-OHP, ΣOH-Phen, ΣOH-Flu and ΣOH-Nap metabolites, respectively (p < 0.001). Analyses of non-smokers revealed weak but significant effects of age, sex, home age, and occupation on urinary levels of selected PAH metabolites (i.e., <7% of observed variation, p < 0.05). The unexplained variation in PAH metabolite levels is most likely related to diet, which was not examined. Although the results revealed significant relationships between urinary PAH metabolite levels and several lifestyle and/or demographic variables, robust examinations of selected effects (e.g., sex, home age, occupation) will require datasets that are balanced with respect to the other highlighted variables. The results can be used to identify remedial measures to reduce exposure and concomitant risk, and/or design follow-up studies to test hypotheses regarding the causes of exposure differences empirically related to sex, age, home age, and occupation.

The association between air pollution and hospitalization for patients with systemic lupus erythematosus in Chile: A daily time series analysis.

Genetic and environmental factors are thought to influence the activity of systemic lupus erythematosus (SLE), but relatively little is known about the effects of ambient air pollution. Using pollution data from air monitoring stations in the urban centers in Santiago Chile, along with daily patient hospitalization data from 2001 to 2012, an association between ambient air pollution and daily hospital admissions for SLE was tested using generalized linear models. Averaged over all regions pollutant mean 24 h concentrations were: 0.96 ppm carbon monoxide (CO), 64 ppb ozone (O3), 43 ppb nitrogen dioxide (NO2), 9 ppb sulphur dioxide (SO2), 29 µg/m3 particulate matter ≤ 2.5 µm in mean aerodynamic diameter (PM2.5), and 67 µg/m3 particulate matter ≤ 10 µm in diameter (PM10). The relative risk estimates in single pollutant models for an interquartile range (IQR) increase in pollutant were: RR = 1.34 (95% CI: 1.06-1.83) for SO2, RR = 1.60 (95% CI: 1.15-2.24) for CO, and RR = 1.41 (95% CI: 1.14-1.86) for PM2.5. In two-pollutant models, the significance of SO2 and PM2.5 persisted despite adjustments for each of the other measured pollutants. These findings suggest that acute increases in air pollution increase the risk of hospitalization with a primary diagnosis of SLE.

Associations between blood volatile organic compounds, and changes in hematologic and biochemical profiles, in a population-based study.

OBJECTIVE: To investigate the influence of volatile organic compound (VOC) levels in blood, on hematological and serum biochemical parameters in the Canadian population. METHODS: We tested the association between seven selected VOCs and hematological profiles and serum tests reflecting liver and kidney function and glucose metabolism using a cross-sectional study design in 3950 participants of the Canadian Health Measures Survey from 2012 to 2015. We used generalized linear mixed models adjusting for age, sex, smoking, alcohol consumption, BMI, education and household income. RESULTS: An increase in blood concentration equivalent to the geometric mean for benzene, ethylbenzene, toluene, m-, p-xylenes, styrene, and total xylenes was associated with 0.68% (95% CI 0.36, 1.0) to 0.91% (95% CI 0.52, 1.3) increase in hemoglobin, and a 1.79% (95% CI 0.96, 2.62) to 4.11% (95% CI 3.11, 5.11) increase in total white blood cell count. Ethylbenzene, toluene, m-, p-xylenes and styrene were positively associated with increased platelet counts. A geometric mean increase for all VOCs was associated with decreases in creatinine. m- and p-xylenes were associated with a significant change in every measured blood cell count and liver function parameter, and in creatinine. Ethylbenzene was also positively associated with an increase in every measured hematologic parameter, two of the three liver function tests, and creatinine. Results were similar when stratified by age, but differed by smoking status and sex. CONCLUSIONS: This study provides evidence that VOCs in blood, at levels found in the Canadian population, may influence blood cell counts and indicators of liver and kidney function, including an inverse association between serum VOC and creatinine. This novel finding merits further investigation to understand the impact of VOCs on human physiology and population health.

Do acute changes in ambient air pollution increase the risk of potentially fatal cardiac arrhythmias in patients with implantable cardioverter defibrillators?

BACKGROUND: Daily changes in ambient air pollution have been associated with cardiac morbidity and mortality. Precipitating a cardiac arrhythmia in susceptible individuals may be one mechanism. We investigated the influence of daily changes in air pollution in the Province of Ontario, Canada on the frequency of discharges from implantable cardio defibrillators (ICDs) which occur in response to potentially life threatening arrhythmias. METHODS: Using a case- crossover design, we compared ambient air pollution concentrations on the day of an ICD discharge to other days in the same month and year in 1952 patients. We adjusted for weather, lagged the exposure data from 0 to 3 days, and stratified the results by several patient-related characteristics. RESULTS: Median (interquartile range) for ozone (O3), fine particulate matter (PM2.5), sulphur dioxide (SO2) and nitrogen dioxide (NO2) were 26.0 ppb (19.4, 33.0), 6.6 µg/m3 (4.3, 10.6), 1.00 ppb (0.4,2.1), 10.0 ppb (6.0,15.3) respectively. Unlagged odds ratios (95%) for an ICD discharge associated with an interquartile range increase in pollutant were 0.97 (0.86, 1.09) for O3, 0.99 (0.92, 1.06) for PM2.5, 0.97 (0.91, 1.03) for SO2, and 1.00 (0.89, 1.12) for NO2. CONCLUSION: We found no evidence that the concentrations of ambient air pollution observed in our study were a risk factor for potentially fatal cardiac arrhythmias in patients with ICDs.

The Association Between Air Pollution and Hospitalization of Patients With Idiopathic Pulmonary Fibrosis in Chile: A Daily Time Series Analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) causes progressive dyspnea, hypoxemia, and death within a few years. Little is known about the effect of air pollution on disease exacerbations. RESEARCH QUESTION: Are acute increases in air pollution a risk factor for hospitalization of patients with a primary diagnosis of IPF. STUDY DESIGN AND METHODS: Hospital admissions for IPF are coded J84.1 by the International Classification of Disease, 10th Revision. Using ambient air pollution and climate data from seven air monitoring stations distributed in the seven urban centers in Santiago, Chile, along with daily patient hospitalization data from 2001 to 2012, a linear association between daily ambient air pollution and daily J84.1 hospital admissions was tested using generalized linear models. RESULTS: Average pollutant levels for all regions were as follows: carbon monoxide was 0.96 ppm, ozone was 64 ppb, nitrogen dioxide (NO2) was 43 ppb, sulfur dioxide was 9 ppb, particulate matter < 2.5 µm in diameter was 29 µg/m3 and particulate matter < 10 µm in diameter (PM10) was 67 µg/m3. For the combined Santiago area, relative risk estimates of J84.1 hospitalizations for all pollutants (except ozone), adjusted for age, sex, and weather were statistically significant. In the two-pollutant models, the significance of NO2 and PM10 persisted despite adjustments for each of the other measured pollutants. INTERPRETATION: Our findings suggest that acute increases in air pollution are a risk factor for hospitalization of patients with a primary diagnosis of IPF.

Correlations of phthalate metabolites in urine samples from fertile and infertile men: Free-form concentration vs. conjugated-form concentration.

In previous studies, the total content of urinary phthalate metabolites was commonly used to evaluate human exposure to phthalates. However, phthalate metabolites are mainly present in urine in two forms, conjugated and free. These metabolite forms in urine are more relevant to the biotransformation pathways of the phthalates in humans. Therefore, the concentration of these forms is more relevant to exposure related health outcomes than total content. In this study, instead of measuring total content, the free- and conjugated-form concentrations of phthalate metabolites in the urine of fertile and infertile men were measured. The main metabolites in urine of both groups are monoethyl phthalate (MEP) and the di-(2-ethylhexyl) phthalate (DEHP) metabolites. The geometric means of their both conjugated- and free-forms in the infertile group were higher than in the fertile group, specifically, 24.3 and 43.4 µg/g creatinine vs 8.5 and 28.9 µg/g creatinine, respectively, for MEP, and 50.0 and 9.1 µg/g creatinine vs 39.1 and 8.4 µg/g creatinine, respectively for total DEHP metabolites. We investigated the correlations of free- and conjugated-form phthalate metabolite concentrations between the infertile and fertile group as well as among different phthalate metabolites. The results showed that there was a statistically significant difference between the infertile and fertile group for monobenzyl phthalate (MBzP) in both free-form and conjugated-form. However, there was only a statistically significant difference between the two groups for conjugated-form MEP and MEHP, and no statistically significant difference between the two groups for free-form MEP and MEHP. The results of the Pearson correlation test revealed that the correlations between DEHP metabolites and the correlations between mid-sized phthalate metabolites (mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP) and mono-benzyl phthalate (MBzP)) were stronger than between these two clusters of metabolites. This study is the first attempt to examine possible effects of conjugated-form concentrations of phthalate metabolites on human fertility. The results of this study suggest that conjugated-form and free-form concentrations of urinary phthalate metabolites may be appropriate biomarkers for assessing human exposure to phthalates and association with health outcomes.

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. Fifty-nine non-smoking participants (mean age 24 years) were randomly assigned to each of two 5-day exposure scenarios: breathing ambient air adjacent to a steel plant or 5 km away at a college campus site. FeNO and on-site air pollutants were measured daily. Mixed effects linear regression models were used for data analysis, adjusting for sex, temperature, humidity and day of week. RESULTS: Compared with the college site, PM 2.5, ultrafine PM, SO2, NO2 and CO levels were significantly greater near the steel plant. FeNO was 15.3% (95% CI, 6.6%, 24.8%) higher near the plant compared to the college site. CONCLUSIONS: Exposure to ambient air near a steel plant was associated with increased airway inflammation as measured by exhaled nitric oxide.

Comparison of tris(2-ethylhexyl) phosphate and di(2-ethylhexyl) phosphoric acid toxicities in a rat 28-day oral exposure study.

Tris(2-ethylhexyl) phosphate (TEHP, CAS no. 78-42-2) is a plasticizer and a flame retardant, while di(2-ethylhexyl) phosphoric acid (DEHPA, CAS no. 298-07-7) is an oil additive and extraction solvent. Publicly-available information on repeated exposure to these two related organophosphate compounds is fragmentary. Hence, adult male and female Fischer rats were exposed to TEHP (300, 1000 and 3000 mg/kg body weight [BW]/day) or DEHPA (20, 60 and 180 mg/kg BW/day) by gavage for 28 consecutive days, to assess and compare their toxicities. Although significantly impaired BW gains and evidence of TEHP enzymatic hydrolysis to DEHPA were observed only in males, exposures to the highest TEHP and DEHPA doses often resulted in similar alterations of hematology, serum clinical chemistry and liver enzymatic activities in both males and females. The squamous epithelial hyperplasia and hyperkeratosis observed in the non-glandular forestomach of rats exposed to the middle and high DEHPA doses were most likely caused by the slightly corrosive nature of this chemical. Although tubular degeneration and spermatid retention were observed only in the testes of males exposed to the highest TEHP dose, numerous periodic acid-Schiff stained crystalline inclusions were observed in testis interstitial cells at all TEHP dose levels. No-observed-adverse-effect levels for TEHP and DEHPA are proposed, but the lower serum pituitary hormone levels resulting from TEHP and DEHPA exposures and the perturbations of testicular histology observed in TEHP-treated males deserve further investigation. Improved characterization of the toxicity of flame retardants will contribute to better informed substitution choices for legacy flame retardants phased-out over health concerns.

Profiles and monthly variations of selected volatile organic compounds in indoor air in Canadian homes: Results of Canadian national indoor air survey 2012-2013.

Volatile organic compounds (VOCs) are important pollutants in indoor air. A major survey campaign was carried out over a 24-month period in 2012 and 2013 to monitor 88 selected VOCs in 3524 Canadian residential homes as part of the Canadian Health Measures Survey (CHMS). Among the 88 VOCs six (limonene, decamethylcyclopentasiloxane, toluene, hexanal, nonanal and α-pinene) were present in the highest concentrations with a combined geometric mean value (63.22 µg/m3) accounting for more than half (54%) of the sum of all 88 VOCs. The geometric means of the majority of the VOCs obtained from this study were not significantly different from the levels of VOCs that were measured in a previous CHMS data collection cycle between 2009 and 2011. This study also further confirmed higher concentrations of the majority of measured VOCs in apartments compared to houses; and of several tobacco-related VOCs (benzene, styrene, naphthalene, 2-butanone, 2-methyl-1,3-butadiene, 2-furancarboxaldehyde, 2,5-dimethylfuran, benzofuran and phenol) in smoking homes. Furthermore, concentrations of aromatic and aliphatic hydrocarbons were higher in winter and in the months of June and July. Oxygenated hydrocarbons such as aldehydes, alcohols and ketones, on the other hand, were found to be higher in warmer months and peaked in summer months. These results provide valuable information on the levels of selected VOCs of which many have been monitored for the first time in Canadian homes, and can be used to estimate population exposure.

Exposure to traffic and mortality risk in the 1991-2011 Canadian Census Health and Environment Cohort (CanCHEC).

There is evidence that local traffic density and living near major roads can adversely affect health outcomes. We aimed to assess the relationship between local road length, proximity to primary highways, and cause-specific mortality in the 1991 Canadian Census Health and Environment Cohort (CanCHEC). In this long-term study of 2.6 million people, based on completion of the long-form census in 1991 and followed until 2011, we used annual residential addresses to determine the total length of local roads within 200 m of postal code representative points and the postal code's distance to primary highways. The association between exposure to traffic and cause-specific non-accidental mortality was estimated using Cox proportional hazards models, adjusting for individual covariates and contextual factors, including census division-level proportion in high school, the percentage of recent immigrants, and neighborhood income. We performed sensitivity analyses, including adjustment for exposure to PM2.5, NO2, or O3, restricting to subjects in core urban areas, and spatial variation by climatic zone. The hazard ratio (HR) for all non-accidental mortality associated with an interquartile increase in length of local roads was 1.05 (95% CI 1.04, 1.05), while for an interquartile range increase in proximity to primary highways, the HR was 1.03 (95% CI 1.02, 1.04). HRs by traffic quartile increased with increasing lengths of local roads, as well as with closer proximity to primary highways, for all mortality causes. The associations were stronger within subjects' resident in urban core areas, attenuated by adjustment for PM2.5, and HRs showed limited spatial variation by climatic zone. In the CanCHEC cohort, exposure to higher road density and proximity to major traffic roads was associated with increased mortality risk from cerebrovascular and cardiovascular disease, ischemic heart disease, COPD, respiratory disease, and lung cancer, with unclear results for diabetes.

Is residential ambient air limonene associated with asthma? Findings from the Canadian Health Measures Survey.

Asthma is a common chronic disease. Exposure to limonene is commonplace because it may be used in the manufacture of personal care products and household cleaners. We investigated the influence of limonene on asthma in a population-based sample of approximately 3000 Canadians. During the Canada Health Measures Survey, carried out between 2012 and 2013, participants were asked if they wheezed or had a diagnosis of asthma, and underwent spirometry and measurement of the fraction of exhaled nitric oxide (FeNO). These variables were tested for an association with limonene concentrations measured in their household air samples, using linear regression analysis A 100% increase in air limonene concentration was associated with an approximate 17% adjusted relative increase wheezing with an odds ratio of 1.17 (95%CI 1.16, 1.18). The percent change in FeNO for a 100% increase in limonene was twice as large for children, 2.89% (95% CI 1.88, 4.43) compared to adults, 1.44% (95%CI 1.16, 1.79). Among boys, the odds ratio was 1.50 (95%CI 1.48, 1.52) between a 100% increase in limonene and a diagnosis of asthma. This study provides evidence that household exposure to limonene may increase the prevalence of asthma in the general population.

Cardiovascular and inflammatory mechanisms in healthy humans exposed to air pollution in the vicinity of a steel mill.

BACKGROUND: There is a paucity of mechanistic information that is central to the understanding of the adverse health effects of source emission exposures. To identify source emission-related effects, blood and saliva samples from healthy volunteers who spent five days near a steel plant (Bayview site, with and without a mask that filtered many criteria pollutants) and at a well-removed College site were tested for oxidative stress, inflammation and endothelial dysfunction markers. METHODS: Biomarker analyses were done using multiplexed protein-array, HPLC-Fluorescence, EIA and ELISA methods. Mixed effects models were used to test for associations between exposure, biological markers and physiological outcomes. Heat map with hierarchical clustering and Ingenuity Pathway Analysis (IPA) were used for mechanistic analyses. RESULTS: Mean CO, SO2 and ultrafine particles (UFP) levels on the day of biological sampling were higher at the Bayview site compared to College site. Bayview site exposures "without" mask were associated with increased (p < 0.05) pro-inflammatory cytokines (e.g IL-4, IL-6) and endothelins (ETs) compared to College site. Plasma IL-1ß, IL-2 were increased (p < 0.05) after Bayview site "without" compared to "with" mask exposures. Interquartile range (IQR) increases in CO, UFP and SO2 were associated with increased (p < 0.05) plasma pro-inflammatory cytokines (e.g. IL-6, IL-8) and ET-1(1-21) levels. Plasma/saliva BET-1 levels were positively associated (p < 0.05) with increased systolic BP. C-reactive protein (CRP) was positively associated (p < 0.05) with increased heart rate. Protein network analyses exhibited activation of distinct inflammatory mechanisms after "with" and "without" mask exposures at the Bayview site relative to College site exposures. CONCLUSIONS: These findings suggest that air pollutants in the proximity of steel mill site can influence inflammatory and vascular mechanisms. Use of mask and multiple biomarker data can be valuable in gaining insight into source emission-related health impacts.

A PCR-based quantitative assay for the evaluation of mRNA integrity in rat samples.

Reverse Transcription quantitative real-time PCR (RT-qPCR) is applied to quantify gene transcript levels in a wide range of investigations. Proper assessment of RNA integrity is essential for reliable assessment of gene expression levels, as RNA molecules are acutely vulnerable to degradation. However, RNA quality control measures are still infrequently reported in rat toxicological studies, which impede proper evaluation of gene expression data reliability. The high operational cost of microfluidic capillary electrophoresis systems along with paucity of alternative methods for the quantitative assessment of rat RNA integrity constitute potential hurdles to the systematic implementation and reporting of RNA integrity assessment in rat studies. This manuscript describes the adaptation of an alternative RT-qPCR-based 3':5' assay as an additional option for the quantitative assessment of rat RNA integrity. Two PCR primer sets were designed on the 3' and 5' regions of a rat housekeeping gene to evaluate RNA integrity by measuring the relative expression (3':5' ratio) of these amplicons. The 3':5' ratios were then compared to Agilent Bioanalyzer's RNA integrity number (RIN) for a wide range of RNA samples originating from different tissues, cultured cell lines and rat strains that were prepared freshly, stored for years at -80 °C, purchased commercially or intentionally degraded. The 3':5' ratios and RIN values presented similar assessment of RNA integrity status from intact to heavily degraded samples. Based on the LOWESS regression of this large comparison dataset, 3':5' ratio threshold criteria equivalent to RIN cut-off values can be proposed for the selection of RNA samples for RT-qPCR analyses. This qPCR-based assay is easy to implement, cost-effective, and provides a reliable quantification of RNA integrity to assist in the selection of rat RNA samples suitable for downstream RT-qPCR gene expression analyses.