Scott Weichenthal

A review of pesticide exposure and cancer incidence in the Agricultural Health Study cohort.

Objective We reviewed epidemiologic evidence related to occupational pesticide exposures and cancer incidence in the Agricultural Health Study (AHS) cohort. Data sources Studies were identified from the AHS publication list available at http://aghealth.nci.nih.gov as well as through a Medline/PubMed database search in March 2009. We also examined citation lists. Findings related to lifetime-days and/or intensity-weighted lifetime-days of pesticide use are the primary focus of this review, because these measures allow for the evaluation of potential exposure–response relationships. Data synthesis We reviewed 28 studies; most of the 32 pesticides examined were not strongly associated with cancer incidence in pesticide applicators. Increased rate ratios (or odds ratios) and positive exposure–response patterns were reported for 12 pesticides currently registered in Canada and/or the United States (alachlor, aldicarb, carbaryl, chlorpyrifos, diazinon, dicamba, S-ethyl-N,N-dipropylthiocarbamate, imazethapyr, metolachlor, pendimethalin, permethrin, trifluralin). However, estimates of association for specific cancers were often imprecise because of small numbers of exposed cases, and clear monotonic exposure–response patterns were not always apparent. Exposure misclassification is also a concern in the AHS and may limit the analysis of exposure–response patterns. Epidemiologic evidence outside the AHS remains limited with respect to most of the observed associations, but animal toxicity data support the biological plausibility of relationships observed for alachlor, carbaryl, metolachlor, pendimethalin, permethrin, and trifluralin. Conclusions Continued follow-up is needed to clarify associations reported to date. In particular, further evaluation of registered pesticides is warranted.

Traffic-Related Air Pollution and Acute Changes in Heart Rate Variability and Respiratory Function in Urban Cyclists

Background: Few studies have examined the acute health effects of air pollution exposures experienced while cycling in traffic. Objectives: We conducted a crossover study to examine the relationship between traffic pollution and acute changes in heart rate variability. We also collected spirometry and exhaled nitric oxide measures. Methods: Forty-two healthy adults cycled for 1 hr on high- and low-traffic routes as well as indoors. Health measures were collected before cycling and 1–4 hr after the start of cycling. Ultrafine particles (UFPs; ≤ 0.1 μm in aerodynamic diameter), particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5), black carbon, and volatile organic compounds were measured along each cycling route, and ambient nitrogen dioxide (NO2) and ozone (O3) levels were recorded from a fixed-site monitor. Mixed-effects models were used to estimate associations between air pollutants and changes in health outcome measures relative to precycling baseline values. Results: An interquartile range increase in UFP levels (18,200/cm3) was associated with a significant decrease in high-frequency power 4 hr after the start of cycling [β = –224 msec2; 95% confidence interval (CI), –386 to –63 msec2]. Ambient NO2 levels were inversely associated with the standard deviation of normal-to-normal (NN) intervals (β = –10 msec; 95% CI, –20 to –0.34 msec) and positively associated with the ratio of low-frequency to high-frequency power (β = 1.4; 95% CI, 0.35 to 2.5) 2 hr after the start of cycling. We also observed significant inverse associations between ambient O3 levels and the root mean square of successive differences in adjacent NN intervals 3 hr after the start of cycling. Conclusions: Short-term exposures to traffic pollution may contribute to altered autonomic modulation of the heart in the hours immediately after cycling.

Selected physiological effects of ultrafine particles in acute cardiovascular morbidity

Ultrafine particles (UFPs) have emerged as a potentially important environmental health concern as they are produced in large numbers by vehicle emissions and may contribute to previously reported associations between traffic pollution and acute cardiovascular morbidity. This review examines recent epidemiological evidence of UFP exposures and selected physiological outcomes that may be modified as part of the underlying causal pathway(s) linking particulate air pollution and acute cardiovascular morbidity. Outcomes examined included changes in heart rate variability (HRV) (autonomic function), ST-segment depression (myocardial ischemia), QT-interval (ventricular repolarization), and endothelial vasomotor function. Twenty-two studies were reviewed in total: 10 prospective panel studies and 12 randomized cross-over studies. Sixteen studies identified a significant relationship between UFPs and at least one of the above outcomes and current evidence generally supports the biological plausibility of a relationship between UFPs and acute cardiovascular morbidity. However, discrepancies were apparent in the direction of observed associations, particularly for HRV and ventricular repolarization. Reasons for these discrepancies may include differences in particle composition, time-point of clinical evaluation, and population susceptibilities. Nevertheless, evidence to date suggests that UFPs have a measureable impact on physiological measures known to be altered in cases of acute cardiovascular morbidity. Moving forward, expanded use of personal exposure measures is recommended for prospective panel studies to minimize exposure misclassification. In addition, effort should be made to include more women in studies of the acute cardiovascular effects of UFPs as findings to date generally reflect responses in men.

PM2.5, oxidant defence and cardiorespiratory health: a review

Airborne fine particle mass concentrations (PM2.5) are used for ambient air quality management worldwide based in part on known cardiorespiratory health effects. While oxidative stress is generally thought to be an important mechanism in determining these effects, relatively few studies have specifically examined how oxidant defence may impact susceptibility to particulate air pollution. Here we review studies that explore the impact of polymorphisms in anti-oxidant related genes or anti-oxidant supplementation on PM2.5-induced cardiorespiratory outcomes in an effort to summarize existing evidence related to oxidative stress defence and the health effects of PM2.5. Recent studies of PM-oxidative burden were also examined. In total, nine studies were identified and reviewed and existing evidence generally suggests that oxidant defence may modify the impact of PM2.5 exposure on various health outcomes, particularly heart rate variability (a measure of autonomic function) which was the most common outcome examined in the studies reviewed. Few studies examined interactions between PM2.5 and oxidant defence for respiratory outcomes, and in general studies focused primarily on acute health effects. Therefore, further evaluation of the potential modifying role of oxidant defence in PM2.5-induced health effects is required, particularly for chronic outcomes. Similarly, while an exposure metric that captures the ability of PM2.5 to cause oxidative stress may offer advantages over traditional mass concentration measurements, little epidemiological evidence is currently available to evaluate the potential benefits of such an approach. Therefore, further evaluation is required to determine how this metric may be incorporated in ambient air quality management.

Long-Term Exposure to Fine Particulate Matter: Association with Nonaccidental and Cardiovascular Mortality in the Agricultural Health Study Cohort

Background: Few studies have examined the relationship between long-term exposure to ambient fine particulate matter (PM2.5) and nonaccidental mortality in rural populations. Objective: We examined the relationship between PM2.5 and nonaccidental and cardiovascular mortality in the U.S. Agricultural Health Study cohort. Methods: The cohort (n = 83,378) included farmers, their spouses, and commercial pesticide applicators residing primarily in Iowa and North Carolina. Deaths occurring between enrollment (1993–1997) and 30 December 2009 were identified by record linkage. Six-year average (2001–2006) remote-sensing derived estimates of PM2.5 were assigned to participants’ residences at enrollment, and Cox proportional hazards models were used to estimate hazard ratios (HR) in relation to a 10-μg/m3 increase in PM2.5 adjusted for individual-level covariates. Results: In total, 5,931 nonaccidental and 1,967 cardiovascular deaths occurred over a median follow-up time of 13.9 years. PM2.5 was not associated with nonaccidental mortality in the cohort as a whole (HR = 0.95; 95% CI: 0.76, 1.20), but consistent inverse relationships were observed among women. Positive associations were observed between ambient PM2.5 and cardiovascular mortality among men, and these associations were strongest among men who did not move from their enrollment address (HR = 1.63; 95% 0.94, 2.84). In particular, cardiovascular mortality risk in men was significantly increased when analyses were limited to nonmoving participants with the most precise exposure geocoding (HR = 1.87; 95% CI: 1.04, 3.36). Conclusions: Rural PM2.5 may be associated with cardiovascular mortality in men; however, similar associations were not observed among women. Further evaluation is required to explore these sex differences. Citation: Weichenthal S, Villeneuve PJ, Burnett RT, van Donkelaar A, Martin RV, Jones RR, DellaValle CT, Sandler DP, Ward MH, Hoppin JA. 2014. Long-term exposure to fine particulate matter: association with nonaccidental and cardiovascular mortality in the Agricultural Health Study Cohort. Environ Health Perspect 122:609–615; http://dx.doi.org/10.1289/ehp.1307277

Exposure to traffic-related air pollution during physical activity and acute changes in blood pressure, autonomic and micro-vascular function in women: a cross-over study

BackgroundTraffic-related air pollution may contribute to cardiovascular morbidity. In urban areas, exposures during physical activity are of interest owing to increased breathing rates and close proximity to vehicle emissions.MethodsWe conducted a cross-over study among 53 healthy non-smoking women in Montreal, Canada during the summer of 2013. Women were exposed to traffic pollutants for 2-hours on three separate occasions during cycling on high and low-traffic routes as well as indoors. Personal air pollution exposures (PM2.5, ultrafine particles (UFP), black carbon, NO2, and O3) were evaluated along each route and linear mixed-effects models with random subject intercepts were used to estimate the impact of air pollutants on acute changes in blood pressure, heart rate variability, and micro-vascular function in the hours immediately following exposure. Single and multi-pollutant models were examined and potential effect modification by mean regional air pollution concentrations (PM2.5, NO2, and O3) was explored for the 24-hour and 5-day periods preceding exposure.ResultsIn total, 143 exposure routes were completed. Each interquartile increase (10,850/cm3) in UFP exposure was associated with a 4.91% (95% CI: -9.31, -0.512) decrease in reactive hyperemia index (a measure of micro-vascular function) and each 24 ppb increase in O3 exposure corresponded to a 2.49% (95% CI: 0.141, 4.84) increase in systolic blood pressure and a 3.26% (95% CI: 0.0117, 6.51) increase in diastolic blood pressure 3-hours after exposure. Personal exposure to PM2.5 was associated with decreases in HRV measures reflecting parasympathetic modulation of the heart and regional PM2.5 concentrations modified these relationships (p < 0.05). In particular, stronger inverse associations were observed when regional PM2.5 was higher on the days prior to the study period. Regional PM2.5 also modified the impact of personal O3 on the standard deviation of normal to normal intervals (SDNN) (p < 0.05): a significant inverse relationship was observed when regional PM2.5 was low prior to study periods and a significant positive relationship was observed when regional PM2.5 was high.ConclusionExposure to traffic pollution may contribute to acute changes in blood pressure, autonomic and micro-vascular function in women. Regional air pollution concentrations may modify the impact of these exposures on autonomic function.

The impact of traffic volume, composition, and road geometry on personal air pollution exposures among cyclists in Montreal, Canada

Cyclists may experience increased exposure to traffic-related air pollution owing to increased minute ventilation and close proximity to vehicle emissions. The aims of this study were to characterize personal exposures to air pollution among urban cyclists and to identify potential determinants of exposure including the type of cycling lane (separated vs on-road), traffic counts, and meteorological factors. In total, personal air pollution exposure data were collected over 64 cycling routes during morning and evening commutes in Montreal, Canada, over 32 days during the summer of 2011. Measured pollutants included ultrafine particles (UFPs), fine particles (PM2.5), black carbon (BC), and carbon monoxide (CO). Counts of diesel vehicles were important predictors of personal exposures to BC, with each 10 vehicle/h increase associated with a 15.0% (95% confidence interval (CI): 5.7%, 24.0%) increase in exposure. Use of separated cycling lanes had less impact on personal exposures with a 12% (95% CI: −43%, 14%) decrease observed for BC and smaller decreases observed for UFPs (mean: −1.3%, 95% CI: −20%, 17%) and CO (mean: −5.6%, 95% CI: −17%, 4%) after adjusting for meteorological factors and traffic counts. On average, PM2.5 exposure increased 7.8% (95% CI: −17%, 35%) with separate cycling lane use, but this estimate was imprecise and not statistically significant. In general, our findings suggest that diesel vehicle traffic is an important contributor to personal BC exposures and that separate cycling lanes may have a modest impact on personal exposure to some air pollutants. Further evaluation is required, however, as the impact of separate cycling lanes and/or traffic counts on personal exposures may vary between regions.

In-Vehicle Exposures to Particulate Air Pollution in Canadian Metropolitan Areas: The Urban Transportation Exposure Study

Commuters may be exposed to increased levels of traffic-related air pollution owing to close proximity to traffic-emissions. We collected in-vehicle and roof-top air pollution measurements over 238 commutes in Montreal, Toronto, and Vancouver, Canada between 2010 and 2013. Voice recordings were used to collect real-time information on traffic density and the presence of diesel vehicles and multivariable linear regression models were used to estimate the impact of these factors on in-vehicle pollutant concentrations (and indoor/outdoor ratios) along with parameters for road type, land use, and meteorology. In-vehicle PM2.5 and NO2 concentrations consistently exceeded regional outdoor levels and each unit increase in the rate of encountering diesel vehicles (count/min) was associated with substantial increases (>100%) in in-vehicle concentrations of ultrafine particles (UFPs), black carbon, and PM2.5 as well as strong increases (>15%) in indoor/outdoor ratios. A model based on meteorology and the length of highway roads within a 500 m buffer explained 53% of the variation in in-vehicle UFPs; however, models for PM2.5 (R(2) = 0.24) and black carbon (R(2) = 0.30) did not perform as well. Our findings suggest that vehicle commuters experience increased exposure to air pollutants and that traffic characteristics, land use, road types, and meteorology are important determinants of these exposures.

A randomized double‐blind crossover study of indoor air filtration and acute changes in cardiorespiratory health in a First Nations community

UNLABELLED Few studies have examined indoor air quality in First Nations communities and its impact on cardiorespiratory health. To address this need, we conducted a crossover study on a First Nations reserve in Manitoba, Canada, including 37 residents in 20 homes. Each home received an electrostatic air filter and a placebo filter for 1 week in random order, and lung function, blood pressure, and endothelial function measures were collected at the beginning and end of each week. Indoor air pollutants were monitored throughout the study period. Indoor PM2.5 decreased substantially during air filter weeks relative to placebo (mean difference: 37 μg/m(3) , 95% CI: 10, 64) but remained approximately five times greater than outdoor concentrations owing to a high prevalence of indoor smoking. On average, air filter use was associated with a 217-ml (95% CI: 23, 410) increase in forced expiratory volume in 1 s, a 7.9-mm Hg (95% CI: -17, 0.82) decrease in systolic blood pressure, and a 4.5-mm Hg (95% CI: -11, 2.4) decrease in diastolic blood pressure. Consistent inverse associations were also observed between indoor PM2.5 and lung function. In general, our findings suggest that reducing indoor PM2.5 may contribute to improved lung function in First Nations communities. PRACTICAL IMPLICATIONS Indoor air quality is known to contribute to adverse cardiorespiratory health, but few studies have examined indoor air quality in First Nations communities. Our findings suggest that indoor PM2.5 may contribute to reduced lung function and that portable air filters may help to alleviate these effects by effectively reducing indoor levels of particulate matter.

Personal exposure to specific volatile organic compounds and acute changes in lung function and heart rate variability among urban cyclists.

BACKGROUND Few studies have examined the acute cardiorespiratory effects of specific volatile organic compound (VOC) exposures from traffic pollution. METHODS A cross-over study was conducted among 42 healthy adults during summer 2010 in Ottawa, Canada. Participants cycled for 1-h along high and low-traffic routes and VOC exposures were determined along each route. Lung function, exhaled nitric oxide, and heart rate variability were monitored before cycling and 1-4h after the start of cycling. Bayesian hierarchical models were used to examine the relationship between 26 VOCs and acute changes in clinical outcomes adjusted for potential confounding factors. RESULTS Each inter-quartile range (IQR) increase in propane/butane exposure was associated with a 2.0 millisecond (ms) (95% CI: 0.65, 3.2) increase in SDNN (standard deviation of normal-to-normal intervals), a 24 ms(2) (95% CI: 6.6, 41) increase in HF (high frequency power), and a 65 ms(2) (95% CI: 11, 118) increase in LF (low frequency power) in the hours following cycling. IQR increases in ethane and isoprene were associated with a 5.8 ms (95% CI: -9.8, -1.7): decrease in SDNN and a 24 ms(2) (95% CI: -44, -7.9) decrease in HF, respectively. IQR increases in benzene exposure were associated with a 1.7 ppb (95% CI: 1.1, 2.3) increase in exhaled nitric oxide and each IQR increase in 3-methylhexane exposure was associated with a 102 mL (95% CI: -157, -47) decrease in forced expiratory volume in 1-s. CONCLUSIONS Exposure to traffic-related VOCs may contribute to acute changes in lung function, inflammation, or heart rate variability.