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).     

Design and sampling methodology for a large study of preschool children's aggregate exposures to persistent organic pollutants in their everyday environments

Young children, because of their immaturity and their rapid development compared to adults, are considered to be more susceptible to the health effects of environmental pollutants. They are also more likely to be exposed to these pollutants, because of their continual exploration of their environments with all their senses. Although there has been increased emphasis in recent years on exposure research aimed at this specific susceptible population, there are still large gaps in the available data, especially in the area of chronic, low-level exposures of children in their home and school environments. A research program on preschool children's exposures was established in 1996 at the USEPA National Exposure Research Laboratory. The emphasis of this program is on children's aggregate exposures to common contaminants in their everyday environments, from multiple media, through all routes of exposure. The current research project, "Children's Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants," (CTEPP), is a pilot-scale study of the exposures of 257 children, ages 1(1/2)-5 years, and their primary adult caregivers to contaminants in their everyday surroundings. The contaminants of interest include several pesticides, phenols, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and phthalate esters. Field recruitment and data collection began in February 2000 in North Carolina and were completed in November 2001 in Ohio. This paper describes the design strategy, survey sampling, recruiting, and field methods for the CTEPP study.     

Children's health and the environment: public health issues and challenges for risk assessment

Infants and children are not little adults. They are uniquely vulnerable to environmental toxicants. To protect infants and children against toxicants, the National Research Council in 1993 called for development of an approach to risk assessment that considers children's unique patterns of exposure and their special vulnerabilities to pesticides. Many aspects of that call were codified into federal law in the Food Quality Protection Act (FQPA) of 1996. This report highlights the central elements needed for development of a child-protective approach to risk assessment: a) improved quantitative assessment of children's exposures at different life stages, from fetal life through adolescence, including acute and chronic exposures, exposures via multiple routes, and exposures to multiple agents; b) development of new approaches to toxicity testing of chemicals that can detect unanticipated and subtle outcomes and that evaluate experimental subjects over the entire life span from early exposure to natural death to replicate the human experience; c) development of new toxicodynamic and toxicokinetic models that account for the unique physiologic characteristics of infants and children; d) development of new approaches to assessment of outcomes, functional, organ, cellular and molecular, over the entire life span; these measures need to be incorporated into toxicity testing and into long-term prospective epidemiologic studies of children; and e) application of uncertainty and safety factors in risk assessment that specifically consider children's risks. Under FQPA, children are presumed more vulnerable to pesticides than adults unless evidence exists to the contrary. Uncertainty and safety factors that are protective of children must therefore be incorporated into risk assessment when data on developmental toxicity are lacking or when there is evidence of developmental toxicity. The adequate protection of children against toxic agents in the environment will require fundamental and far-reaching revisions of current approaches to toxicity testing and risk assessment.     

Quantitative analysis of children's microactivity patterns: The Minnesota Children's Pesticide Exposure Study.

The National Human Exposure Assessment Survey (NHEXAS)/Minnesota Children's Pesticide Exposure Study (MNCPES) was a population-based study designed to characterize children's exposure to residential pesticides and to evaluate the contribution of residential and children's activities to children's exposure. Families of 168 children were surveyed for residential use of pesticides and children's activities. From these homes, families of 102 children between the ages of 3 and 13 years participated in a week-long intensive exposure study. Of the 102 children, 19 children were videotaped for four consecutive hours in their normal daily activities. The survey responses indicated that the youngest children were more likely to exhibit behaviors that would foster exposure to environmental contaminants. Comparison of questionnaire responses indicated that the videotaped subsample was representative of the exposure study population. The microactivities of the videotaped children that might contribute to their exposure via ingestion or dermal routes were quantified. Hand-to-mouth and object-to-mouth activities were observed most frequently among the youngest children. The youngest children were also most likely to be barefoot both indoors and outside. Gender differences were found in mouthing behavior and the proportion of observed time spent outdoors.     

Lessons learned for the assessment of children's pesticide exposure: critical sampling and analytical issues for future studies

In this article we examine sampling strategies and analytical methods used in a series of recent studies of children's exposure to pesticides that may prove useful in the design and implementation of the National Children's Study. We focus primarily on the experiences of four of the National Institute of Environmental Health Sciences/U.S. Environmental Protection Agency/ Children's Centers and include University of Washington studies that predated these centers. These studies have measured maternal exposures, perinatal exposures, infant and toddler exposures, and exposure among young children through biologic monitoring, personal sampling, and environmental monitoring. Biologic monitoring appears to be the best available method for assessment of children's exposure to pesticides, with some limitations. It is likely that a combination of biomarkers, environmental measurements, and questionnaires will be needed after careful consideration of the specific hypotheses posed by investigators and the limitations of each exposure metric. The value of environmental measurements, such as surface and toy wipes and indoor air or house dust samples, deserves further investigation. Emphasis on personal rather than environmental sampling in conjunction with urine or blood sampling is likely to be most effective at classifying exposure. For infants and young children, ease of urine collection (possible for extended periods of time) may make these samples the best available approach to capturing exposure variability of nonpersistent pesticides; additional validation studies are needed. Saliva measurements of pesticides, if feasible, would overcome the limitations of urinary metabolite-based exposure analysis. Global positioning system technology appears promising in the delineation of children's time-location patterns.     

Environmental exposure and children's health in China

Concerns regarding adverse health effects of exposure to environmental pollutants among children are increasing. This subject area is particularly important in China because of environmental pollution problems associated with rapid development and a large population. The authors provide what is, to their knowledge, the first review in China of English- and Chinese-language literature regarding the current status of environmental exposures to children in China and the impact of these exposures on the health of children. Children in China are exposed to diverse environmental pollutants, including traditional pollutants such as lead and mercury and emerging pollutants such as phthalates and perfluorinated compounds. Incidence and prevalence of certain childhood diseases have increased in last decades. In China, a limited number of data on environmental exposure and children's health are available, and further high-quality studies are needed.     

Chemical wastes, children''s health, and the Superfund Basic Research Program.

Three to 4 million children and adolescents in the United States live within 1 mile of a federally designated Superfund hazardous waste disposal site and are at risk of exposure to chemical toxicants released from these sites into air, groundwater, surface water, and surrounding communities. Because of their patterns of exposure and their biological vulnerability, children are uniquely susceptible to health injury resulting from exposures to chemical toxicants in the environment. The Superfund Basic Research Program, funded by the U.S. Environmental Protection Agency and directed by the National Institute of Environmental Health Sciences, is extremely well positioned to organize multidisciplinary research that will assess patterns of children's exposures to hazardous chemicals from hazardous waste disposal sites; quantify children's vulnerability to environmental toxicants; assess causal associations between environmental exposures and pediatric disease; and elucidate the mechanisms of environmental disease in children at the cellular and molecular level.     

Characterizing exposures to nonpersistent pesticides during pregnancy and early childhood in the National Children's Study: a review of monitoring and measurement methodologies

The National Children's Study is a proposed longitudinal cohort study to evaluate the relationships between children's health and the environment. Enrollment is estimated to begin in September 2005, and 100,000 children will be followed from preconception or early pregnancy until adulthood. Among multiple health outcomes, the study is proposing to investigate whether pre- and/or postnatal exposures to nonpersistent pesticides increase the risk of poor performance on neurobehavioral and cognitive exams during infancy and early childhood. Characterization of exposures will be challenging. Nonpersistent pesticides include many chemicals with biologic half-lives on the order of hours or days. Exposures can occur through multiple pathways (e.g., food and residential or agriculture pesticide use) and by multiple routes (inhalation, ingestion, dermal). Effects may depend on the developmental stage when exposure occurs. Sequential sampling is likely to be required and may involve a combination of environmental and biologic monitoring as well as collection of questionnaire data. In this article we review measurements that can be used to characterize exposures. These include biologic markers, personal and indoor air sampling techniques, collection of dust, surface and dermal wipe samples, and dietary assessment tools. Criteria for sample selection will necessitate evaluation of the time frame of exposure captured by the measurement in relationship to critical windows of susceptibility, the cost and validity of the measurements, participant burden, and variability in exposure routes across populations and at different age periods.     

Exposure assessment in the National Children's Study: introduction

The science of exposure assessment is relatively new and evolving rapidly with the advancement of sophisticated methods for specific measurements at the picogram per gram level or lower in a variety of environmental and biologic matrices. Without this measurement capability, environmental health studies rely on questionnaires or other indirect means as the primary method to assess individual exposures. Although we use indirect methods, they are seldom used as stand-alone tools. Analyses of environmental and biologic samples have allowed us to get more precise data on exposure pathways, from sources to concentrations, to routes, to exposure, to doses. They also often allow a better estimation of the absorbed dose and its relation to potential adverse health outcomes in individuals and in populations. Here, we make note of various environmental agents and how best to assess exposure to them in the National Children's Study--a longitudinal epidemiologic study of children's health. Criteria for the analytical method of choice are discussed with particular emphasis on the need for long-term quality control and quality assurance measures.     

The National Children's Study of environmental effects on child health and development

Increasing recognition that children may be more susceptible than adults to environmental exposures and that they experience potentially life-long consequences of such exposures has led to widespread support for a large new cohort study in the United States. In this article, we propose a framework for a new cohort study of children, with follow-up beginning before birth and continuing to age 21 years. We also describe the administrative structure that has been built to develop the proposal further. The structure includes a partnership between federal and nonfederal scientists and relies on a collaborative, interdisciplinary research effort of unprecedented scale in medical research. We discuss briefly how the proposed cohort could be used to examine, among many other things, the effect of chemical contaminants in breast milk on children's health and development.     

Environmental exposure and birth outcomes

The influence of environmental hazards on the health of children is one of the major current concerns in environmental health. Scientific investigations are now focusing on identifying and understanding the role of environmental hazards in the development of birth outcomes that result from in utero exposure to environmental contaminants. This paper reviews the published literature with provided evidence concerning the impact of environmental exposures to chemicals on the incidence of birth outcomes in the areas of environmental pollution originating from various sources. In spite of methodological limitations in a number of reviewed studies, the present body of knowledge calls for a precautionary approach and for preventive measures in order to reduce the risk of environmental exposures to chemicals with a recognized or suspected potential to cause birth outcomes.     

Socioeconomic position and exposure to multiple environmental chemical contaminants in six European mother-child cohorts

BackgroundHuman exposure to environmental chemical contaminants at critical periods of development can lead to lifelong health consequences. Traditionally, socioeconomically disadvantaged groups are thought to experience higher contaminant exposures; however, this relationship may not hold for all contaminants.MethodsUsing data from six European birth cohorts (1301 mother-child pairs), we determined biomarkers of exposure to 41 contaminants in biological samples from children (6–12 years) and their mothers during pregnancy, including organochlorine compounds (OCs), polybrominated diphenyl ethers (PBDEs), per- and polyfluoroalkyl substances (PFASs), metals, phthalate metabolites, phenols, and organophosphate (OP) pesticide metabolites. We analyzed these biomarkers with several socioeconomic position (SEP) indicators (maternal education, employment status and family affluence scale).ResultsHigher SEP was associated with higher concentrations of several chemicals during pregnancy, including certain PFASs, mercury, arsenic, several phenols, and OP pesticides. Similarly, childhood concentrations of OCs, PFASs, mercury, arsenic, and bisphenol A were higher in higher SEP groups. Conversely, cadmium exposure during pregnancy and exposure to lead and phthalate metabolites in childhood were higher in lower SEP. Principal components representing multiple pollutant exposures showed similar association with SEP.ConclusionsThis study demonstrates that environmental chemical contaminant exposure during fetal and childhood life is not exclusively associated to lower SEP and that for several contaminants higher SEP groups incur higher exposure levels.     

Community-based exposure estimate for hydrogen sulfide

Indoor and outdoor air pollution monitoring may indicate potential human exposure to air contaminants. Individual and population exposures to air contaminants depend upon many factors including time spent outdoors and indoors, permeability of housing structures, and mobility within a community. In this report, we illustrate an approach for using long-term air monitoring to establish patterns or changes of environmental exposures, improve validity and representativeness of data, and prevent exposure misclassification. Long-term air monitoring for hydrogen sulfide (H2S) at 14 Dakota City, Nebraska, residences identified differences in area-wide concentration levels, geographic locations, and seasonal exposures. Air data for 1999 indicated that Dakota City residents were repeatedly exposed, both indoors and outdoors, to moderate levels (>or=90 parts per billion [ppb]) of H2S. Using GIS modeling and kriging, we produced a geographic gradient of exposure estimate or map for ambient H2S. These findings formed the basis for designing two health investigations for this community.     

Children's exposure to traffic and pedestrian injuries.

OBJECTIVES: The purpose of this study was to estimate children's exposure to traffic (number of streets crossed) and to determine the role of exposure in pedestrian injury. METHODS: Questionnaires were distributed to a random sample of 4080 first- and fourth-grade children in 43 Montreal schools. RESULTS: When analyzed by police district, injury and exposure rates were positively correlated (r2 = 0.53). Crossings were similar by sex but increased with age and were inversely related to socioeconomic status. CONCLUSIONS: These results suggest that although children's exposure to traffic could be reduced by transporting them to school, a more reasonable prevention strategy involves environmental changes.     

Quantifying children's aggregate (dietary and residential) exposure and dose to permethrin: application and evaluation of EPA's probabilistic SHEDS-Multimedia model

Reliable, evaluated human exposure and dose models are important for understanding the health risks from chemicals. A case study focusing on permethrin was conducted because of this insecticide's widespread use and potential health effects. SHEDS-Multimedia was applied to estimate US population permethrin exposures for 3- to 5-year-old children from residential, dietary, and combined exposure routes, using available dietary consumption data, food residue data, residential concentrations, and exposure factors. Sensitivity and uncertainty analyses were conducted to identify key factors, pathways, and research needs. Model evaluation was conducted using duplicate diet data and biomonitoring data from multiple field studies, and comparison to other models. Key exposure variables were consumption of spinach, lettuce, and cabbage; surface-to-skin transfer efficiency; hand mouthing frequency; fraction of hand mouthed; saliva removal efficiency; fraction of house treated; and usage frequency. For children in households using residential permethrin, the non-dietary exposure route was most important, and when all households were included, dietary exposure dominated. SHEDS-Multimedia model estimates compared well to real-world measurements data; this exposure assessment tool can enhance human health risk assessments and inform children's health research. The case study provides insights into children's aggregate exposures to permethrin and lays the foundation for a future cumulative pyrethroid pesticides risk assessment.     

Environmental exposure assessment in European birth cohorts: results from the ENRIECO project

Environmental exposures during pregnancy and early life may have adverse health effects. Single birth cohort studies often lack statistical power to tease out such effects reliably. To improve the use of existing data and to facilitate collaboration among these studies, an inventory of the environmental exposure and health data in these studies was made as part of the ENRIECO (Environmental Health Risks in European Birth Cohorts) project. The focus with regard to exposure was on outdoor air pollution, water contamination, allergens and biological organisms, metals, pesticides, smoking and second hand tobacco smoke (SHS), persistent organic pollutants (POPs), noise, radiation, and occupational exposures. The review lists methods and data on environmental exposures in 37 European birth cohort studies. Most data is currently available for smoking and SHS (N=37 cohorts), occupational exposures (N=33), outdoor air pollution, and allergens and microbial agents (N=27). Exposure modeling is increasingly used for long-term air pollution exposure assessment; biomonitoring is used for assessment of exposure to metals, POPs and other chemicals; and environmental monitoring for house dust mite exposure assessment. Collaborative analyses with data from several birth cohorts have already been performed successfully for outdoor air pollution, water contamination, allergens, biological contaminants, molds, POPs and SHS. Key success factors for collaborative analyses are common definitions of main exposure and health variables. Our review emphasizes that such common definitions need ideally be arrived at in the study design phase. However, careful comparison of methods used in existing studies also offers excellent opportunities for collaborative analyses. Investigators can use this review to evaluate the potential for future collaborative analyses with respect to data availability and methods used in the different cohorts and to identify potential partners for a specific research question.     

Outdoor, indoor, and personal exposure to VOCs in children

We measured volatile organic compound (VOC) exposures in multiple locations for a diverse population of children who attended two inner-city schools in Minneapolis, Minnesota. Fifteen common VOCs were measured at four locations: outdoors (O), indoors at school (S), indoors at home (H), and in personal samples (P). Concentrations of most VOCs followed the general pattern O approximately equal to S < P less than or equal to H across the measured microenvironments. The S and O environments had the smallest and H the largest influence on personal exposure to most compounds. A time-weighted model of P exposure using all measured microenvironments and time-activity data provided little additional explanatory power beyond that provided by using the H measurement alone. Although H and P concentrations of most VOCs measured in this study were similar to or lower than levels measured in recent personal monitoring studies of adults and children in the United States, p-dichlorobenzene was the notable exception to this pattern, with upper-bound exposures more than 100 times greater than those found in other studies of children. Median and upper-bound H and P exposures were well above health benchmarks for several compounds, so outdoor measurements likely underestimate long-term health risks from children's exposure to these compounds.     

Time-activity patterns of pregnant women and changes during the course of pregnancy

Numerous studies suggest that in utero exposures to environmental contaminants are associated with fetal development, congenital anomalies, learning difficulties or other health impacts later in life. Although location and time-activity data have been used to model exposure to specific contaminants in epidemiological studies, little information is available about time-activity patterns of pregnant women. We measured changes in location-based activity patterns over the course of pregnancy (48-h periods, during two or three trimesters) using a self-reported time-activity log among a nonrandom sample of pregnant women (n=62). We assessed the influence of demographics and personal factors on changes in activity over pregnancy using mixed effects regression models. Increasing weeks of pregnancy was a significant predictor for increased time spent at home (1 h/day increase for each trimester of pregnancy), after adjusting for income (2.6 more h/day at home in lowest income group), work status (3.5 more h/day at home for nonworkers) and other children in the family (1.5 more h/day at home with other children). No other measured activities (time outdoors, time in transit modalities or time in other indoor locations) were related to weeks of pregnancy. As our results indicate that pregnant women tend to spend more time at home during the latter stages of pregnancy, future exposure and epidemiological research should consider the potential increase in home-based exposures (i.e., indoor air pollution or chemicals in the home) late in pregnancy, and increased confidence in exposure proxies based on home locations or characteristics during the same period.     

Children's environmental health in agricultural settings

Children residing in rural settings may encounter environmental hazards derived from agricultural production activities. Health consequences of organic dusts, farm chemicals including pesticides, machinery noise, excess sun exposure, and zoonotic infectious agents have been clearly described among farm-working adults. The author reviews the related evidence base on child health with a life-stage perspective on their differential exposure and vulnerabilities. Methemoglobinemia among infants consuming nitrate-contaminated well water, neurodevelopmental health impacts associated with early life exposure to organophosphate pesticides, and diarrheal disease due to zoonotic infectious agents are well-described pediatric concerns. There is suggestive but more limited evidence for respiratory health consequences from air contaminants associated with confined animal feeding operations and hearing deficits for children exposed to machinery-related noise. Many contaminants of concern for children in these environments remain largely understudied-diesel exhaust, biomass burning, solvents, veterinary antibiotics, and silica-containing particulate matter. Overall, the state of knowledge and programmatic activities on agriculturally derived environmental contaminants and child health is immature and much less complete than for working adults. This overview provides a context for research, policy, and programmatic needs.     

Children's cognition and aircraft noise exposure at home--the West London Schools Study

The association of aircraft noise exposure with cognitive performance was examined by means of a cross-sectional field survey. Two hundred thirty six children attending 10 primary schools around Heathrow Airport in west London were tested on reading comprehension, immediate/delayed recall and sustained attention. In order to obtain the information about their background, a questionnaire was delivered to the parents and 163 answers were collected. Logistic regression models were used to assess performance on the cognitive tests in relation to aircraft noise exposure at home and possible individual and school level confounding factors. A significant dose-response relationship was found between aircraft noise exposure at home and performance on memory tests of immediate/delayed recall. However there was no strong association with the other cognitive outcomes. These results suggest that aircraft noise exposure at home may affect children's memory.