National Human Exposure Assessment Survey: analysis of exposure pathways and routes for arsenic and lead in EPA Region 5.

The National Human Exposure Assessment Survey (NHEXAS) Phase I field study conducted in EPA Region 5 (Great Lakes Area) provides extensive exposure data on a representative sample of approximately 250 residents of the region. Associated environmental media and biomarker (blood, urine) concentration data were also obtained for the study participants to aid in understanding of the relationships of exposures to both contaminant pathways and doses. Besides fulfilling the primary NHEXAS objectives, the NHEXAS data provided an opportunity to explore secondary usages, such as examining pathway to route of exposure relationships. A generic type of structural equation model was used to define the anticipated relationships among the various data types for both arsenic (As) and lead (Pb). Since, by design, only a few participants provided data for all sample types, implementing this model required that some media concentrations (outdoor air and soil) be imputed for subjects with missing information by using measurements collected in the same geographic area and time period. The model, and associated pairwise correlations, generally revealed significant but weak associations among the concentrations, exposures, and doses; the strongest associations occurred for the various air measurements (indoor versus outdoor and personal). The generally weak associations were thought to be partly due to the absence of complete coverage of nonresidential environmental media and to nonsynchronization of relevant measurement times and integration periods of collection across the various sample types. In general, relationships between the NHEXAS questionnaire data and the various concentration, exposure, and body-burden measures were also weak. The model results and the modeling exercise suggest several ways for optimizing the design of future exposure assessment studies that are aimed at supporting structural modeling activities.

Measurement of children's exposure to pesticides: analysis of urinary metabolite levels in a probability-based sample.

The Minnesota Children's Pesticide Exposure Study is a probability-based sample of 102 children 3-13 years old who were monitored for commonly used pesticides. During the summer of 1997, first-morning-void urine samples (1-3 per child) were obtained for 88% of study children and analyzed for metabolites of insecticides and herbicides: carbamates and related compounds (1-NAP), atrazine (AM), malathion (MDA), and chlorpyrifos and related compounds (TCPy). TCPy was present in 93% of the samples, whereas 1-NAP, MDA, and AM were detected in 45%, 37%, and 2% of samples, respectively. Measured intrachild means ranged from 1.4 microg/L for MDA to 9.2 microg/L for TCPy, and there was considerable intrachild variability. For children providing three urine samples, geometric mean TCPy levels were greater than the detection limit in 98% of the samples, and nearly half the children had geometric mean 1-NAP and MDA levels greater than the detection limit. Interchild variability was significantly greater than intrachild variability for 1-NAP (p = 0.0037) and TCPy (p < 0.0001). The four metabolites measured were not correlated within urine samples, and children's metabolite levels did not vary systematically by sex, age, race, household income, or putative household pesticide use. On a log scale, mean TCPy levels were significantly higher in urban than in nonurban children (7.2 vs. 4.7 microg/L; p = 0.036). Weighted population mean concentrations were 3.9 [standard error (SE) = 0.7; 95% confidence interval (CI), 2.5, 5.3] microg/L for 1-NAP, 1.7 (SE = 0.3; 95% CI, 1.1, 2.3) microg/L for MDA, and 9.6 (SE = 0.9; 95% CI, 7.8, 11) microg/L for TCPy. The weighted population results estimate the overall mean and variability of metabolite levels for more than 84,000 children in the census tracts sampled. Levels of 1-NAP were lower than reported adult reference range concentrations, whereas TCPy concentrations were substantially higher. Concentrations of MDA were detected more frequently and found at higher levels in children than in a recent nonprobability-based sample of adults. Overall, Minnesota children's TCPy and MDA levels were higher than in recent population-based studies of adults in the United States, but the relative magnitude of intraindividual variability was similar for adults and children.

An assessment of the data quality for NHEXAS--Part I: Exposure to metals and volatile organic chemicals in Region 5.

A National Human Exposure Assessment Survey (NHEXAS) was performed in U.S. Environmental Protection Agency (U.S. EPA) Region V, providing population-based exposure distribution data for metals and volatile organic chemicals (VOCs) in personal, indoor, and outdoor air, drinking water, beverages, food, dust, soil, blood, and urine. One of the principal objectives of NHEXAS was the testing of protocols for acquiring multimedia exposure measurements and developing databases for use in exposure models and assessments. Analysis of the data quality is one element in assessing the performance of the collection and analysis protocols used in NHEXAS. In addition, investigators must have data quality information available to guide their analyses of the study data. At the beginning of the program quality assurance (QA) goals were established for precision, accuracy, and method quantification limits. The assessment of data quality was complicated. First, quality control (QC) data were not available for all analytes and media sampled, because some of the QC data, e.g., precision of duplicate sample analysis, could be derived only if the analyte was present in the media sampled in at least four pairs of sample duplicates. Furthermore, several laboratories were responsible for the analysis of the collected samples. Each laboratory provided QC data according to their protocols and standard operating procedures (SOPs). Detection limits were established for each analyte in each sample type. The calculation of the method detection limits (MDLs) was different for each analytical method. The analytical methods for metals had adequate sensitivity for arsenic, lead, and cadmium in most media but not for chromium. The QA goals for arsenic and lead were met for all media except arsenic in dust and lead in air. The analytical methods for VOCs in air, water, and blood were sufficiently sensitive and met the QA goals, with very few exceptions. Accuracy was assessed as recovery from field controls. The results were excellent (> or = 98%) for metals in drinking water and acceptable (> or = 75%) for all VOCs except o-xylene in air. The recovery of VOCs from drinking water was lower, with all analytes except toluene (98%) in the 60-85% recovery range. The recovery of VOCs from drinking water also decreased when comparing holding times of < 8 and > 8 days. Assessment of the precision of sample collection and analysis was based on the percent relative standard deviation (% RSD) between the results for duplicate samples. In general, the number of duplicate samples (i.e., sample pairs) with measurable data were too few to assess the precision for cadmium and chromium in the various media. For arsenic and lead, the precision was excellent for indoor, and outdoor air (< 10% RSD) and, although not meeting QA goals, it was acceptable for arsenic in urine and lead in blood, but showed much higher variability in dust. There were no data available for metals in water and food to assess the precision of collection and analysis.

Use of a pharmacokinetic model to assess chlorpyrifos exposure and dose in children, based on urinary biomarker measurements.

Chlorpyrifos is a common agricultural insecticide and has been used residentially in the United States until the year 2000 when this use was restricted by the U.S. Environmental Protection Agency (U.S. EPA). A chlorpyrifos metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) has been found in urine samples collected during exposure field studies. In this work, we use urinary biomarker data and the inverse solution of a simple pharmacokinetic (PK) model for chlorpyrifos to estimate the magnitude and timing of doses. Three urine samples were collected on separate days from each of 15 children (ages 3-12) who were participants in the Minnesota Children's Pesticide Exposure Study (MNCPES). The total volume of urine was noted and samples analyzed for TCPY: The urinary data was used along with constraints imposed on dose timing, based on responses of the individuals to pesticide-use surveys. We predicted the time and magnitude of multiple "event" exposures characterized by short-term, relatively high doses superimposed over a continuous background exposure. The average dose of chlorpyrifos predicted by the model was 1.61 microg/kg per reported event. Average background dose rate for these children that reported exposure events was 0.0062 microg/kg/h, or 0.15 microg/kg/day. In addition to predicting the total dose of chlorpyrifos received by an individual from urinary biomarker measurements, the model can then be run in a forward manner once the exposure regime is determined. This will allow the prediction of the total amount of TCPy eliminated in the urine over any time period of interest.

Design strategy for assessing multi-pathway exposure for children: the Minnesota Children's Pesticide Exposure Study (MNCPES).

Although children are exposed to a variety of environmental hazards, including pesticides, there is a scarcity of information available to estimate exposures realistically. This article reports on one of the first attempts to measure multi-pathway pesticide exposures in a population-based sample of urban and non-urban children. A design strategy was developed to assess multi-pathway pesticide exposures in children using personal exposure measurements in combination with complimentary measurements of biological markers of exposure, concentrations in relevant environmental media, and time spent in important microenvironments and participating in exposure-related activities. Sample collection and analysis emphasized measurement of three insecticides (i.e., chlorpyrifos, diazinon, and malathion) and one herbicide (i.e., atrazine). These compounds were selected because of their frequent use, presence in multiple environmental media, expected population exposures, and related hazard/toxicity. The study was conducted during the summer of 1997 in Minnesota and involved a stratified sample of households with children ages 3-12 years. Participants resided in either (a) the cities of Minneapolis and St. Paul (urban households), or (b) Rice and Goodhue Counties just south of the metropolitan area (non-urban households). Results from a residential inventory documenting storage and use of products containing the target pesticides were used to preferentially select households where children were likely to have higher exposures. The study successfully obtained pesticide exposure data for 102 children, including measurements of personal exposures (air, hand rinse, duplicate diet), environmental concentrations (residential indoor/outdoor air, drinking water, residential surfaces, soil), activity patterns (obtained by questionnaire, diary, videotaping), and internal dose (metabolites in urine).

Pesticide storage and use patterns in Minnesota households with children.

As part of the National Human Exposure Assessment Survey (NHEXAS), residential pesticide storage and use patterns were evaluated in a population-based sample of Minnesota households with children aged 3-13. In-home interviews and inventories were conducted to identify pesticide products stored and used in and around 308 households. This statistically based sample represents more than 49,000 urban and rural households in the census tracts sampled. More than 850 unique products were identified using Environmental Protection Agency (EPA) registration numbers. Pesticide products were found in 97% and reported used in 88% of study households. Population-weighted mean values for pesticide storage and use were 6.0 and 3.1 products per household, respectively. The most common active ingredients found were diethyl toluamide (DEET) and related compounds, piperonyl butoxide, pyrethrins, dimethylamine 2-[2-methyl-4-chlorophenoxyl propionate (MCPA) and chlorpyrifos. Household socio-demographic characteristics explained little of the variability in pesticide storage and use patterns, and there were no significant differences in residential storage and use patterns between households located in urban versus non-urban census tracts. Although the prevalence of households with pesticide products was similar to recent national surveys, observed storage and use rates were almost twice those obtained in recent national studies, reflecting improved inventory techniques used by this study and/or increased rates of pesticide presence and use in study households.

Measurement of multi-pollutant and multi-pathway exposures in a probability-based sample of children: practical strategies for effective field studies.

The purpose of this manuscript is to describe the practical strategies developed for the implementation of the Minnesota Children's Pesticide Exposure Study (MNCPES), which is one of the first probability-based samples of multi-pathway and multi-pesticide exposures in children. The primary objective of MNCPES was to characterize children's exposure to selected pesticides through a combination of questionnaires, personal exposure measurements (i.e., air, duplicate diet, hand rinse), and complementary monitoring of biological samples (i.e., pesticide metabolites in urine), environmental samples (i.e., residential indoor/outdoor air, drinking water, dust on residential surfaces, soil), and children's activity patterns. A cross-sectional design employing a stratified random sample was used to identify homes with age-eligible children and screen residences to facilitate oversampling of households with higher potential exposures. Numerous techniques were employed in the study, including in-person contact by locally based interviewers, brief and highly focused home visits, graduated subject incentives, and training of parents and children to assist in sample collection. It is not feasible to quantify increases in rates of subject recruitment, retention, or compliance that resulted from the techniques employed in this study. Nevertheless, results indicate that the total package of implemented procedures was instrumental in obtaining a high percentage of valid samples for targeted households and environmental media.

Sampling design, response rates, and analysis weights for the National Human Exposure Assessment Survey (NHEXAS) in EPA region 5.

For the Phase I field test of the National Human Exposure Assessment Survey (NHEXAS) in U.S. Environmental Protection Agency (EPA) Region 5, this paper presents the survey sampling design, the response rates achieved, and the sample weighting procedure implemented to compensate for unit nonresponse. To enable statistically defensible inferences to the entire region, a sample of about 250 members of the household population in EPA Region 5 was selected using a stratified multistage probability-based survey sampling design. Sample selection proceeded in four nested stages: (1) sample counties; (2) area segments based on Census blocks within sample counties; (3) housing units (HUs) within sample segments; and (4) individual participants within sample households. Each fourth-stage sample member was asked to participate in 6 days of exposure monitoring. A subsample of participants was asked to participate in two rounds of longitudinal follow-up data collection. Approximately 70% of all sample households participated in household screening interviews in which rosters of household members were developed. Over 70% of the sample subjects selected from these households completed the Baseline Questionnaire regarding their demographic characteristics and potential for exposures. And, over 75% of these sample members went on to complete at least the core environmental monitoring, including personal exposures to volatile organic compounds (VOCs) and tap water concentrations of metals. The sample weighting procedures used the data collected in the screening interviews for all household members to fit logistic models for nonresponse in the later phases of the study. Moreover, the statistical analysis weights were poststratified to 1994 State population projections obtained from the Bureau of the Census to ensure consistency with other statistics for the Region.

National Human Exposure Assessment Survey (NHEXAS): distributions and associations of lead, arsenic and volatile organic compounds in EPA region 5.

The National Human Exposure Assessment Survey (NHEXAS) Phase I field study conducted in EPA Region 5 provides extensive exposure data on approximately 250 study participants selected via probability sampling. Associated environmental media and biomarker (blood, urine) concentration data were also obtained to aid in the understanding of relationships of the exposures to both contaminant sources and doses. Distributional parameters for arsenic (As), lead (Pb), and four volatile organic compounds (VOCs)--benzene, chloroform, tetrachloroethylene, and trichloroethylene--were estimated for each of the relevant media using weighted data analysis techniques. Inter-media associations were investigated through correlation analysis, and longitudinal correlations and models were used to investigate longitudinal patterns. Solid food appeared to be a major contributor to urine As levels, while Pb levels in household (HH) dust, personal air, and beverages all were significantly associated with blood Pb levels. Relatively high (>0.50) longitudinal correlations were observed for tap water Pb and As, as compared to only moderate longitudinal correlations for the personal air VOCs.

Diurnal variation of PEF and its use in epidemiological studies.

Diurnal variability in peak expiratory flow (PEF) has been an accepted clinical method in the management of asthma and the evaluation of occupational asthma. In this paper, the basis for this usage together with other clinical and epidemiological applications is discussed. The measured characteristics of PEF diurnal variability are described in asthmatics and asymptomatic subjects, showing the greater variability in asthmatics, and the "morning dip" related to circadian rhythm. PEF measured by pneumotachograph and the mini-Wright meter are shown to be in good agreement, but PEF measured by the latter and other small PEF meters is different in terms of absolute values, and both intraindividual variability within test sets and diurnally. The use of PEF meters, and the daily diaries in which the subject or patient records PEF and related factors are described.

Relation of peak expiratory flow rates and symptoms to ambient ozone.

The temporal association between peak expiratory flow rates (PEFRs) and ambient ozone (O3) was studied in a group of 287 children and 523 nonsmoking adults in Tucson. In children, noon PEFRs were decreased on days when there was a higher O3 concentration; children with physician-confirmed asthma experienced the greatest decrease in noon PEFR. Evening PEFR levels were also significantly related to O3 in children, especially asthmatics. Among adults, evening PEFRs were decreased in asthmatics who spent more time outdoors on days when O3 levels were higher. After we adjusted for covariates, significant effects of interactions of 8-h O3 levels with particulate matter (PM10) and temperature on daily PEFR were found. There was some overnight effect of 8-h O3 on morning PEFRs. In general, the respiratory response to low-level ambient O3 is acute, occurs more in asthmatics, and increases as temperature and PM10 increase.

Multipollutant exposures and health responses to particulate matter.

Epidemiological methods provide opportunities to study interactions of pollutants in complex environments. During the study of health and the environment and the evaluation of particulate matter in Tucson, we found that type, location, and temporality of particulate matter exposures were critical with respect to the various interactions that related to health effects. Indoor particulate matter interacted with other components of particulate matter found in tobacco smoke, as evidenced by lung function. The interaction of environmental tobacco smoke with indoor formaldehyde caused various symptoms. Other interactions occurred between indoor and outdoor forms of particulate matter, which caused symptoms in some of the subjects.

Respiratory symptoms and risk factors in an Arizona population sample of Anglo and Mexican-American whites.

Prevalence rates of respiratory symptoms and diseases in a large group of Anglos and Mexican-Americans were analyzed. Each subject completed a questionnaire. Among current smokers, chronic productive cough and dyspnea were significantly higher in both ethnic groups; wheezy symptoms were higher in Anglos. There were no significant differences in the symptom prevalence rates between the two groups, after stratifying by current cigarette consumption and CRT. The spirometric values were not significantly different. In both ethnic groups, the prevalence rates of wheeze, SOBWHZ and asthma were significantly higher in those who had CRT. Among Anglos, less educated smokers had significantly higher prevalence rates of SOBWHZ and dyspnea; nonsmokers with less education had higher prevalence rates of cough, chronic cough and dyspnea. Our results confirm the importance of CRT and lower educational level as risk factors for respiratory symptoms. Ethnicity is not associated with symptomatology or lung function impairment.

The normal range of diurnal changes in peak expiratory flow rates. Relationship to symptoms and respiratory disease.

Measuring peak expiratory flow rates (PEFR) several times a day can provide an objective assessment of functional changes relative to environmental or occupational exposures. This report describes the pattern of diurnal changes in PEFR in a reference population, and defines ranges of "normal" between- and within-day variability. An index of diurnal changes was defined as the ratio between maximal and minimal values, where the maximal value was restricted to PEFR measured at noon or in the evening (N, E) and the minimal value was restricted to the morning or at bedtime (M, B). A ratio greater than normal represented an exaggeration of the normal diurnal pattern in PEFR. Normal limits, based on the ninety-fifth percentile in the reference population, were larger for children (130%) than for adults 15 to 35 yr of age (117%) and those older than 35 yr of age (118%). The meaningfulness of excessive diurnal changes in PEFR was examined by relating this ratio (Max/Min), and a similar measure (the amplitude percent mean) to chronic respiratory symptoms and diseases in 938 adults and children who recorded PEFR values 2 to 4 times per day for as long as 14 days. There was a strong relationship of diurnal changes in PEFR that exceed normal limits with physician-confirmed asthma (relative risk of 2.99 with Max/Min), with exertional dyspnea (Grade 2+), and with more frequent reporting of acute symptoms of wheeze, attacks of wheezing dyspnea, cough, and chest colds. In addition, those exceeding the normal limits had about 2.9 times greater risk of having a FEV1 below 80% of predicted, and nearly 7 times greater risk of being below 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Exposure assessment approaches to evaluate respiratory health effects of particulate matter and nitrogen dioxide.

Several approaches can be taken to estimate or classify total personal exposures to air pollutants. While personal exposure monitoring (PEM) provides the most direct measurements, it is usually not practical for extended time periods or large populations. This paper describes the use of indirect approaches to estimate total personal exposure for NO2 and particulate matter (PM), summarizes the distributions of these estimates, and compares the effectiveness of these estimates with microenvironmental concentrations for evaluating effects on respiratory function and symptoms. Pollutant concentrations were measured at several indoor and outdoor locations for over 400 households participating in an epidemiological study in Tucson, Arizona. Central site monitoring data were significantly correlated with samples collected directly outside homes, but the former usually had higher pollutant concentrations. Integrated indices of daily total personal exposure were calculated using micro-environmental (ME) measurements or estimates and time-budget diary information. Peak expiratory flow rates (PEFR) were measured for up to four times a day during two-week study periods. In thirty children (ages 6-15 years) with current diagnosed asthma, a significant reduction in PEFR was associated with NO2 levels measured outside of their homes. Additional decrements of morning PEFR were found in those children sleeping in bedrooms with higher measured NO2 levels. Morning and noon PEFR decrements were also linked to higher morning NO2 levels that were measured at central monitoring stations. Effects of PM were also found, but were limited to morning PEFR. No effects were found in non-asthmatic children. The relationship of PEFR to the calculated indices of daily average total exposure were weaker than to the microenvironment concentrations. This suggests that diary and ME monitoring data need to yield better time resolution in order to incorporate short-term average exposures to higher concentrations into the exposure indices and into the analysis of within day health responses.

Chronic respiratory effects of indoor formaldehyde exposure.

The relation of chronic respiratory symptoms and pulmonary function to formaldehyde (HCHO) in homes was studied in a sample of 298 children (6-15 years of age) and 613 adults. HCHO measurements were made with passive samplers during two 1-week periods. Data on chronic cough and phlegm, wheeze, attacks of breathlessness, and doctor diagnoses of chronic bronchitis and asthma were collected with self-completed questionnaires. Peak expiratory flow rates (PEFR) were obtained during the evenings and mornings for up to 14 consecutive days for each individual. Significantly greater prevalence rates of asthma and chronic bronchitis were found in children from houses with HCHO levels 60-120 ppb than in those less exposed, especially in children also exposed to environmental tobacco smoke. In children, levels of PEFR decreased linearly with HCHO exposure, with the estimated decrease due to 60 ppb of HCHO equivalent to 22% of PEFR level in nonexposed children. The effects in asthmatic children exposed to HCHO below 50 ppb were greater than in healthy ones. The effects in adults were less evident: decrements in PEFR due to HCHO over 40 ppb were seen only in the morning, and mainly in smokers.

The new standard environmental inventory questionnaire for estimation of indoor concentrations.

Several investigators have developed indoor air quality questionnaires for use in field studies. The approach used in many of them have numerous features in common, but most of them are unique in their content (wording, format, item selection). It is thought that indoor air quality research could be greatly advanced if the primary or fundamental questions and instruments could be consolidated. The use of a basic set of "standard" questions would permit intercomparison of results from different research studies. It is generally agreed that environmental inventory questionnaires (EIQ) help to classify, at least in screening, relative concentration estimates, which precede exposure estimation. Thus, such instruments are not equivalent to monitoring for exposure assessment. However, data linkage and mega data bases are important for some comparative analyses of exposure assessment and exposure-response relationships. Standard instruments such as the EIQ are useful as a screening device to precede other tests to allow identification of potentially high exposure situations. They can also amplify information from other tests. General usage of standard questionnaires and protocols can lead to cumulative improvements in data collection, specificity and effectiveness. This has been the rationale for the present efforts by investigators to form a standardized environmental inventory questionnaire, under the auspices of the U.S. Environmental Protection Agency (EPA), Gas Research Institute (GRI), and Electric Power Research Institute (EPRI).