Stephen Graham

Using human activity data in exposure models: Analysis of discriminating factors

This paper tests factors thought to be important in explaining the choices people make in where they spend time. Three aggregate locations are analyzed: outdoors, indoors, and in-vehicles for two different sample groups: a year-long (longitudinal) sample of one individual and a cross-sectional sample of 169 individuals from the US Environmental Protection Agencys Consolidated Human Activity Database (CHAD). The cross-sectional sample consists of persons similar to the longitudinal subject in terms of age, work status, education, and residential type. The sample groups are remarkably similar in the time spent per day in the tested locations, although there are differences in participation rates: the percentage of days frequenting a particular location. Time spent outdoors exhibits the most relative variability of any location tested, with in-vehicle time being the next. The factors found to be most important in explaining daily time usage in both sample groups are: season of the year, season/temperature combinations, precipitation levels, and day-type (work/nonwork is the most distinct, but weekday/weekend is also significant). Season, season/temperature, and day-type are also important for explaining time spent indoors. None of the variables tested are consistent in explaining in-vehicle time in either the cross-sectional or longitudinal samples. Given these findings, we recommend that exposure modelers subdivide their population activity data into at least season/temperature, precipitation, and day-type “cohorts” as these factors are important discriminating variables affecting where people spend their time.

Developing meaningful cohorts for human exposure models

This paper summarizes numerous statistical analyses focused on the US Environmental Protection Agencys Consolidated Human Activity Database (CHAD), used by many exposure modelers as the basis for data on what people do and where they spend their time. In doing so, modelers tend to divide the total population being analyzed into “cohorts”, to reduce extraneous interindividual variability by focusing on people with common characteristics. Age and gender are typically used as the primary cohort-defining attributes, but more complex exposure models also use weather, day-of-the-week, and employment attributes for this purpose. We analyzed all of these attributes and others to determine if statistically significant differences exist among them to warrant their being used to define distinct cohort groups. We focused our attention mostly on the relationship between cohort attributes and the time spent outdoors, indoors, and in motor vehicles. Our results indicate that besides age and gender, other important attributes for defining cohorts are the physical activity level of individuals, weather factors such as daily maximum temperature in combination with months of the year, and combined weekday/weekend with employment status. Less important are precipitation and ethnic data. While statistically significant, the collective set of attributes does not explain a large amount of variance in outdoor, indoor, or in-vehicle locational decisions. Based on other research, parameters such as lifestyle and life stages that are absent from CHAD might have reduced the amount of unexplained variance. At this time, we recommend that exposure modelers use age and gender as “first-order” attributes to define cohorts followed by physical activity level, daily maximum temperature or other suitable weather parameters, and day type possibly beyond a simple weekday/weekend classification.

Pyrethroid pesticides and their metabolites in vacuum cleaner dust collected from homes and day-care centers

Urinary metabolites of pyrethroid pesticides have been used as biomarkers to estimate human exposure to the parent insecticide. It is important to establish whether these markers are present in environments or media to which humans are exposed routinely. Failure to account for the contribution of pre-existing markers to urinary concentrations could result in risk assessments that overestimate exposure. The purpose of this study was to quantify the concentrations of 13 selected pyrethroid pesticides and their degradation products in samples of indoor dust that had been collected in vacuum cleaner bags during the childrens total exposure to persistent pesticides and other persistent organic pollutants (CTEPP) study of homes and day cares in North Carolina and Ohio. Sieved contents of 85 vacuum cleaner bags were analyzed, and permethrin was found in all samples. Sixty-nine samples contained at least one additional pyrethroid, but none contained more than five pyrethroids in detectable concentrations. Resmethrin, prallethrin, and fenpropathrin were not detected in any samples, while 36 contained phenothrin. The median concentration of permethrin in the samples was 1454ng/g of dust. Excluding permethrin, pyrethroid concentrations were typically less than or equal to 100ng/g of dust. The majority of degradates were present in more than half of the dust samples, usually at concentrations of less than or equal to 100ng/g of dust. For those pyrethroids with a characteristic oxydibenzene group, the cyclopropane degradates were present at higher concentrations than the corresponding benzoic acid moieties. Using urinary concentrations of these metabolites to model human exposure to the parent pyrethroids, may over-estimate risk due to the presence of pre-existing degradates in dust.

Measurement of pyrethroids and their environmental degradation products in fresh fruits and vegetables using a modification of the quick easy cheap effective rugged safe (QuEChERS) method.

Pyrethroid insecticides are used extensively in agriculture, and they, as well as their environmental degradates, may remain as residues on foods such as fruits and vegetables. Since pyrethroid degradates can be identical to the urinary markers used in human biomonitoring, it is important to understand the contribution of these degradates when studying sources of human pyrethroid exposure. We modified the widely used Quick Easy Cheap Effective Rugged Safe (QuEChERS) method to measure several current-use pyrethroids (cis/trans-permethrin, cypermethrin, deltamethrin, esfenvalerate, bifenthrin, cyfluthrin, and cyhalothrin) and their environmental degradation products (3-PBA, cis/trans-DCCA, 4-F-3-PBA, DBCA, and MPA) in selected fresh fruits and vegetables. Using fortified samples, we determined extraction efficiencies from: tomatoes, oranges (whole, peeled, and rind), grapes, apples, bananas (peeled and rind only), onions, lettuce, green peppers, carrots and broccoli. For a subset of these food items (apples, grapes, tomatoes, lettuce and banana peel), we also established limits of detection (MDLs) and quantitation (MQLs). Each sample was homogenized (1kg) then spiked with the target pyrethroids and their degradation products. Sub-samples (15g) were extracted with acetonitrile, then salted out and partitioned with NaCl and MgSO4. The extract was divided and further cleaned using solid phase extraction (SPE) cartridges containing either graphitized non-porous carbon (pyrethroids) or C18 (degradation products). Sample analysis was via liquid chromatography/tandem mass spectrometry (LC-MS/MS). Considering the mean recoveries each of the 14 analytes in all 13 matrices: 42% of the recoveries were ≥90%, 70% were ≥80%, and 90% were ≥70%. All MDLs were less than 100ng/kg, except 3-PBA (132ng/kg, tomato), MPA (129ng/kg, tomato), and trans-permethrin (141ng/kg, banana peel). We then applied the method to non-spiked samples (subset of 5 for which the MDLs/MQLs had been determined) collected weekly for four weeks from local supermarkets. At least one pyrethroid was present in measureable concentrations in all matrices except banana peels. In contrast, the only degradation products detected were cis/trans-DCCA, in one lettuce sample.

Development and evaluation of alternative approaches for exposure assessment of multiple air pollutants in Atlanta, Georgia

Measurements from central site (CS) monitors are often used as estimates of exposure in air pollution epidemiological studies. As these measurements are typically limited in their spatiotemporal resolution, true exposure variability within a population is often obscured, leading to potential measurement errors. To fully examine this limitation, we developed a set of alternative daily exposure metrics for each of the 169 ZIP codes in the Atlanta, GA, metropolitan area, from 1999 to 2002, for PM2.5 and its components (elemental carbon (EC), SO4), O3, carbon monoxide (CO), and nitrogen oxides (NOx). Metrics were applied in a study investigating the respiratory health effects of these pollutants. The metrics included: (i) CS measurements (one CS per pollutant); (ii) air quality model results for regional background pollution; (iii) local-scale AERMOD air quality model results; (iv) hybrid air quality model estimates (a combination of (ii) and (iii)); and (iv) population exposure model predictions (SHEDS and APEX). Differences in estimated spatial and temporal variability were compared by exposure metric and pollutant. Comparisons showed that: (i) both hybrid and exposure model estimates exhibited high spatial variability for traffic-related pollutants (CO, NOx, and EC), but little spatial variability among ZIP code centroids for regional pollutants (PM2.5, SO4, and O3); (ii) for all pollutants except NOx, temporal variability was consistent across metrics; (iii) daily hybrid-to-exposure model correlations were strong (r>0.82) for all pollutants, suggesting that when temporal variability of pollutant concentrations is of main interest in an epidemiological application, the use of estimates from either model may yield similar results; (iv) exposure models incorporating infiltration parameters, time-location-activity budgets, and other exposure factors affect the magnitude and spatiotemporal distribution of exposure, especially for local pollutants. The results of this analysis can inform the development of more appropriate exposure metrics for future epidemiological studies of the short-term effects of particulate and gaseous ambient pollutant exposure in a community.

Environmentally relevant mixing ratios in cumulative assessments: A study of the kinetics of pyrethroids and their ester cleavage metabolites in blood and brain; and the effect of a pyrethroid mixture on the motor activity of rats

UNLABELLED National surveys of United States households and child care centers have demonstrated that pyrethroids are widely distributed in indoor habited dwellings and this suggests that co-exposure to multiple pyrethroids occurs in nonoccupational settings. The purpose of this research was to use an environmentally relevant mixture of pyrethroids to assess their cumulative effect on motor activity and develop kinetic profiles for these pyrethroids and their hydrolytic metabolites in brain and blood of rats. Rats were dosed orally at one of two levels (1.5× or 5.0× the calculated dose that decreases rat motor activity by 30%) with a mixture of cypermethrin, deltamethrin, esfenvalerate, cis-/trans-permethrin, and β-cyfluthrin in corn oil. At 1, 2, 4, 8, or 24h after dosing, the motor activity of each animal was assessed and the animals sacrificed. Concentrations of pyrethroids in brain and blood, and the following metabolites: cis-/trans-dichlorovinyl-dimethylcyclopropane-carboxylic acid, 3-phenoxybenzoic acid, 3-phenoxybenzyl alcohol, 4-fluoro-3-phenoxybenzoic acid, and cis-dibromovinyl-dimethylcyclopropane-carboxylic acid were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS). Using this pyrethroid mixture in rats, the results suggest there is greater metabolism of trans-permethrin prior to entering the systemic circulatory system. All pyrethroids had tissue half-lives (t1/2) of less than 5h, excepting esfenvalerate in brain. At early time points, relative pyrethroid brain concentrations approximated their dose mixture proportions and a sigmoidal Emax model described the relationship between motor activity decrease and total pyrethroid brain concentration. In blood, the t1/2s of the cyclopropane metabolites were longer than the phenoxybenzoic metabolites. However, relative to their respective precursors, concentrations of the phenoxybenzoic acids were much higher than concentrations of the cyclopropane metabolites. Brain concentrations of all metabolites were low relative to blood concentrations. This implies limited metabolite penetration of the blood-brain barrier and little metabolite formation within the brain. IN CONCLUSION toxicokinetic differences between the pyrethroids did not appear to be important determinants of their relative potency and their effect on motor activity was consistent with a pyrethroid dose additive model.

Statistical properties of longitudinal time-activity data for use in human exposure modeling

Understanding the longitudinal properties of the time spent in different locations and activities is important in characterizing human exposure to pollutants. The results of a four-season longitudinal time-activity diary study in eight working adults are presented, with the goal of improving the parameterization of human activity algorithms in EPA’s exposure modeling efforts. Despite the longitudinal, multi-season nature of the study, participant non-compliance with the protocol over time did not play a major role in data collection. The diversity (D)—a ranked intraclass correlation coefficient (ICC)— and lag-one autocorrelation (A) statistics of study participants are presented for time spent in outdoor, motor vehicle, residential, and other-indoor locations. Day-type (workday versus non-workday, and weekday versus weekend), season, temperature, and gender differences in the time spent in selected locations and activities are described, and D & A statistics are presented. The overall D and ICC values ranged from approximately 0.08–0.26, while the mean population rank A values ranged from approximately 0.19–0.36. These statistics indicate that intra-individual variability exceeds explained inter-individual variability, and low day-to-day correlations among locations. Most exposure models do not address these behavioral characteristics, and thus underestimate population exposure distributions and subsequent health risks associated with environmental exposures.

A test house study of pesticides and pesticide degradation products following an indoor application

UNLABELLED Preexisting pesticide degradates are a concern for pesticide biomonitoring studies as exposure to them may result in overestimation of pesticide exposure. The purpose of this research was to determine whether there was significant formation and movement, of pesticide degradates over a 5-week period in a controlled indoor setting after insecticide application. Movement of the pesticides during the study was also evaluated. In a simulated crack and crevice application, commercially available formulations of fipronil, propoxur, cis/trans-permethrin, and cypermethrin were applied to a series of wooden slats affixed to the wall in one room of an unoccupied test house. Floor surface samples were collected through 35 days post-application. Concentrations of the pesticides and the following degradates were determined: 2-iso-propoxyphenol, cis/trans 3-(2,2-dichlorovinyl)-3-3-dimethyl-(1-cyclopropane) carboxylic acid, 3-phenoxybenzoic acid, fipronil sulfone, fipronil sulfide, and fipronil desulfinyl. Deltamethrin, which had never been applied, and chlorpyrifos, which had been applied several years earlier, and their degradation products, cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid, and, 3,5,6-trichloro-2-pyridinol, respectively, were also measured. Propoxur was the only insecticide with mass movement away from the application site. There was no measurable formation or movement of the degradates. However, all degradates were present at low levels in the formulated product. These results indicate longitudinal repetitive sampling of indoor degradate levels during short-term studies, is unnecessary. PRACTICAL IMPLICATIONS Exposure to preexisting pesticide degradates may inflate estimates of exposure in biomonitoring studies where these compounds are used as biomarkers. To date, there is no published information on formation of pesticide degradates following an indoor application. We found that the study pesticides have low rates of degradation and are unlikely to be a significant factor affecting results of short-term (weeks) biomonitoring studies. Therefore, relatively few indoor samples are needed to estimate background levels of degradation products resulting from a recent pesticide application.

Using paired soil and house dust samples in an in vitro assay to assess the post ingestion bioaccessibility of sorbed fipronil

For children, ingestion of soils and house dusts can be an important exposure pathway for regulated organic compounds. Following ingestion, the extent to which compounds desorb and become bioaccessible is a critical determinant of systemic adsorption. We characterized the physicochemical properties of 37 soil and house dust pairs collected during a national survey of United States homes. For each sample, we measured the bioaccessibility of fipronil, a phenylpyrazole insecticide using an in vitro, three- compartment digestive system, then modeled the physicochemical predictors of fipronil bioaccessibility. The properties of the soils and dusts were not correlated and percent carbon was the only significant predictor of bioaccessibility for both soils (p<0.001) and dusts (p<0.001). The carbon content of the soils (3.1±2.4%) was lower than that of the dusts (18.6±6.9%) Due to the lower carbon content, soil sorbed fipronil was more bioaccessible than dust sorbed fipronil. However, the slope of the bioaccessibility carbon regression line was steeper for the soils than for the house dusts. This suggested that, for soils having carbon percentages greater than those in this study, fipronil bioaccessibility may be less than that of house dusts having equal carbon content.

Characterizing the impact of projected changes in climate and air quality on human exposures to ozone

The impact of climate change on human and environmental health is of critical concern. Population exposures to air pollutants both indoors and outdoors are influenced by a wide range of air quality, meteorological, behavioral, and housing-related factors, many of which are also impacted by climate change. An integrated methodology for modeling changes in human exposures to tropospheric ozone (O3) owing to potential future changes in climate and demographics was implemented by linking existing modeling tools for climate, weather, air quality, population distribution, and human exposure. Human exposure results from the Air Pollutants Exposure Model (APEX) for 12 US cities show differences in daily maximum 8-h (DM8H) exposure patterns and levels by sex, age, and city for all scenarios. When climate is held constant and population demographics are varied, minimal difference in O3 exposures is predicted even with the most extreme demographic change scenario. In contrast, when population is held constant, we see evidence of substantial changes in O3 exposure for the most extreme change in climate. Similarly, we see increases in the percentage of the population in each city with at least one O3 exposure exceedance above 60 p.p.b and 70 p.p.b thresholds for future changes in climate. For these climate and population scenarios, the impact of projected changes in climate and air quality on human exposure to O3 are much larger than the impacts of changing demographics. These results indicate the potential for future changes in O3 exposure as a result of changes in climate that could impact human health.