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PublicationsPesticides and Human Health Research ORD/NCER STAR GRANTS
Introduction The research projects described below are funded by NCER grants. For ease of understanding, all grants have been placed under topic areas that describe the overall, general objectives of the projects. Specific information is given for each grant that includes: title, web address, EPA grant number, principal investigator(s), institution (university), NCER project officer, dates during which the grant is funded, and a brief description of the research. Science Questions and Issues that NCER Is Addressing Related to Pesticides and Human Health
WHAT RESEARCH IS STAR FUNDING ON FARMWORKER/CHILDREN'S EXPOSURE TO PESTICIDES IN AGRICULTURAL AREAS? Pesticide Exposure Pathways for Farmworkers' Children in Yakima
Valley, Washington This study will evaluate the contribution of several environmental exposure pathways to children's pesticide exposure. This study will aim to quantify spatial and temporal variability in pesticide residues in and around residences of farmworker children. Research will also characterize child activities during periods of residential pesticide contamination and during periods when children have access to recently pesticide-treated areas. 1. The Epidemiological Investigation of the Effects of Pesticide
Exposure on Neurodevelopmental, Growth, and Respiratory Health of
Farmworker Children Environmental Exposures to Children Living in an Agricultural Community
– This component of the study focuses on children's exposures
to pesticides, pollens, molds, dusts, and other allergens. Specific
activities involve measuring urinary levels of organophosphate pesticide
metabolites in approximately 500 pregnant women and their children,
and comparing these levels to local pesticide use, including home
and agricultural use. As of January 10, 2000, approximately 120
women had been enrolled. Fellowship - Probabilistic Analysis of Fieldworker Exposure
to Azinphos Methyl The goal of this research is to analyze the tools that are available to predict absorbed dose following dermal exposure of agricultural workers to pesticide residues. Ingestion of Pesticides by Children in an Agricultural Community
on the U.S./Mexico Border The objective of this research is to develop an observational model of pesticide exposure in children (ages 18 to 48 months) living in a rural agricultural setting utilizing objective measures of pesticides on children's hands, characterization of frequency and sequencing of 4 behaviors (hand to mouth, hand to object, hand to surface, and object to mouth). Exposure of Children to Pesticides in Yuma County, Arizona This project will study 300 children recruited from the Valley Health Clinic a primary care provider that serves primarily low-income Hispanic and Cocopah. A pesticide use questionnaire will be administered in the clinic and 100 families will be selected for multi-media sampling for pyrethroids and OPs in their homes. All 300 children will be evaluated for cholinesterase inhibitors. Vulnerability of Young Children to Organophosphate Pesticides
and Selected Metals Through Intermittent Exposures in Yuma County,
Arizona Our goal is the accurate determination of the pesticide routes and amounts of exposure experienced by young children. We will measure rates of dermal contact, hand to mouth, and mouthing activity among children using video tape methods. We will evaluate media contacted by children (air, house dust, hands) for concentrations of 9 OP pesticides commonly used in the area (including chlorpyrifos, diazinon and malathion). Lead, manganese and other metals will be measured in house dust by XRF. WHAT RESEARCH IS STAR FUNDING ON CHILDREN AND PESTICIDE EXPOSURE IN URBAN AREAS? Growing Up Health In East Harlem: Pesticide Exposure The centerpiece of the Center is the Community-Based Prevention Research Project, "Growing Up Healthy in East Harlem". The goal of this project is to reduce exposures of inner-city children and their families to pesticides in city housing through the technique of Integrated Pest Management (IPM) and to reduce exposure to PCBs through dietary modification. Epidemiologic Research: Pesticides and Neurological Development Two epidemiologic research projects seek to determine whether pesticides and PCBs have adverse effects on the neurological development of children in the inner city and whether these effects are still evident in adult life. Health Effects of HAPs Among Inner Urban School Children This study will examine the association between exposure to a variety of HAPs (volatile organic chemicals, metals, pesticides) and adverse effects on children's health. The primary hypothesis to be tested is that documented HAP exposures (using air monitoring data, personal air samples, and biologic markers of exposure) are not associated with measured health effects in inner urban children. School-Based Study of Complex Environmental Exposures and Related
Health Effects in Children Part A - Exposure The objectives of this study are to (1) document complex exposure patterns involving multiple acute exposures and exposures to chemical mixtures for school children (K - 5) from two low-income, racially diverse neighborhoods in Minneapolis, (2) examine temporal variability by monitoring complex exposures three times over a twelve-month period, (3) apportion the relative contribution to measured personal exposure of outdoor community air, air inside the child's school, and air inside the child's residence, (4) evaluate the relationship between measured exposures and internal dose using biological markers of exposure in blood and urine, and (5) compare children's exposures between a new school designed to enhance indoor air quality and an older school with more traditional architecture, mechanical systems, and furnishings. PESTICIDE EXPOSURE IN CHILDREN IN URBAN VERSUS RURAL OR HOME ENVIRONMENTS Total Organophosphate (OP) Pesticide Exposure Among Children
in Urban and Rural Environments This study has two primary objectives: 1) characterization of geographic,
temporal, age-related, and gender-related variability in total OP
pesticide exposure in children; and 2) determination of the relative
contributions of environmental sources to total OP pesticide body
burden in children. 1998 Progress Report: Measuring and Apportioning Children's
Exposure to Pesticides in Urban, Suburban, and Rural Communities The purpose of this study is to: 1) measure 'total' exposure (i.e., all important pathways to selected pesticides for a sample of children living in central-city, suburban, and rural neighborhoods in Minnesota; 2) identify and quantify relative contributions of important pathways/sources to measured exposures; and 3) compare children's pesticide exposure between an inner-city urban area, a suburban neighborhood, and a rural agricultural community. A tota; l of 477 households were identified that meet study criteria. From this sub-sample 308 homes were visited and pesticide inventories conducted by the Minnesota Department of Health. Subjects for the intensive monitoring were obtained from this population, and the following samples were collected from 102 subjects/homes over a six day period: tap water, personal, indoor and outdoor air, surface wipes and press samples, dermal rinses, soils, and food and beverages. Blood, urine, and hair samples were collected from most subjects. Study of Exposure and Body Burden of Children of Different Ages
to Pesticides in the Environment The main objective of the proposed program is to test the hypothesis that children have significantly higher environmental exposures and resulting doses than do adults living in the same home. The study design will be able to test if the distribution of exposures for children living in urban environments is different from children living in rural environments. 1998 Progress Report: Assessing Levels of Organophosphorus Insecticides
That Could Expose Children From Pets Treated With Flea Control Insecticides Data evaluation indicates that, similar to the results seen with
the chlorpyrifos dip during the first grant year, the dislodgable
residues from the phosmet dip also were high initially and dissipated
rapidly. The residues from the phosmet dip were higher than those
from the chlorpyrifos dip probably because the concentration of
active ingredient in the dipping solution was higher Publications/Presentations: Boone JS, Tyler T, Chambers JE. Dislodgeable fur residues and plasma cholinesterase inhibition in dogs treated with flea control dip containing chlorpyrifos. Presented at the Society of Toxicology's annual meeting, Seattle, WA, March 1998. DO PESTICIDES HAVE DEVELOPMENTAL EFFECTS? Polychlorinated Biphenyl and Polychlorinated Dibenzofuran Biomarkers
of Risk Assessment in Adolescent Children and their Mothers This is two cohort comparison study of endocrine and cytochrome P450 family 1 biomarkers for risk assessment of polychlorinalted biphenyls (PCBs)/polychlorinated dibenzofurans (PCDFs) induced developmental toxicities in the human. The subjects will be sexually mature adolescents exposed to high levels of PCBs/PCDFs since conception and their mothers. 1999 Progress Report: Developmental Effects of Fish-Borne
Toxicants in the Rat Epidemiological studies suggest an association between consumption of contaminated Great Lakes fish by pregnant women and behavioral deficits in their children. Preliminary contaminant characterization of salmon has been completed and includes PCBs, pesticides, dioxins, dibenzofurans, inorganic metals, and methylmercury. Publications/Presentations: Bemis JC, Seegal RF. Polychlorinated biphenyls and methylmercury act synergistically to reduce rat brain dopamine content in vitro. Environmental Health Perspectives 1999;107:879-885. Widholm JJ, Seo BW, Roegge CS, Crofton KM, Schantz SL. Aroclor 1254 impairs spatial discrimination-reversal learning in rats. Presented at the 23rd Annual Neurobehavioral Teratology Society Meeting, Keystone, CO, 1999. Seegal RF. PCBs and methylmercury synergistically alter dopamine and intracellular calcium in vitro. Presented at the 17th International Neurotoxicology Conference, Children's Health and the Environment—Mechanisms and Consequences of Developmental Neurotoxicology, Little Rock, AR, 1999. Bemis JC, Seegal RF. Polychlorinated biphenyls and methylmercury increase intracellular calcium content in rat cerebellar granule cells. Neurotoxicology (submitted for publication). Widholm JJ, Clarkson GB, Strupp BJ, Crofton KM, Seegal RF, Schantz SL. Spatial reversal learning in Aroclor 1254 or dioxin-exposed rats: in-depth analysis of response patterns reveals sex-specific deficits in associative ability and inhibitory control in Aroclor 1254-exposed rats. Toxicology and Applied Pharmacology (in preparation). Paraoxonase Polymorphism: Role in Neurodevelopmental Susceptibility
to Organophosphates In this project, the role of age dependent differences in paraoxonase metabolism of organophosphate and metabolic polymorphisms on organophosphate toxicity will be evaluated. Thus, both age and genetic polymorphism will be evaluated in the context of potential factors impacting the susceptibility of children to organophosphate neurodevelopmental toxicity. Fellowship - Developmental Neurotoxicity of Chlorpyrifos: Mechanisms
and Consequences The goal of this research is to examine the adverse effects of chlorpyrifos exposure on brain development. WHAT ARE THE POTENTIAL EFFECTS OF PESTICIDES AS ENDOCRINE DISRUPTORS? 1999 Progress Report: Species-Specific Endocrine Disruption:
PCB- and PAH-Induced Estrogenic Effects This research aims to examine the alleged estrogen receptor-mediated activities of selected environmentally relevant compounds using a combination of in vitro and in vivo assays. These studies are being performed in a number of species, including fish, frogs, mice, and birds, to test the following general hypothesis: rodents are not appropriate surrogates for identifying and assessing the risks of alleged environmental estrogens to human and wildlife health due to a lack of significant amino acid sequence homology between species in the estrogen receptor (ER) ligand binding domains. See web site for extensive list of publications related to this research Endocrine Disruption in Adolescence This research will investigate the effects of the estrogenic agent methoxychlor (MXC) on adolescence by using a nonhuman primate model that adequately represents the prolonged and complex adolescent period of humans. Effects of Early Exposure to Xenoestrogens on the Prostate Gland
Past work with animal models has clearly indicated that brief exposure to natural estrogens during the early developmental period results in permanent alterations of the prostate and dysplasia, hyperplasia and adenoma formation with aging. The present project is designed to test the hypothesis that exposure to certain environmental xenoestrogens during the developmental critical period also permanently imprints the fate of the prostate gland and promotes dysplasia or tumor formation with aging. Effects of an Endocrine Disruptor on Prostate Development and
Growth This research will test the hypothesis that feeding pregnant mice
low, environmentally relevant doses of the pesticide methoxychlor
(MC), or diethylstilbestrol, will result in changes in the Molecular Genetic Research: Variation in Susceptibility to Pesticides This study will evaluate genotypic and phenotypic heterogeneity in the enzymes that activate and detoxify the oxons of chlorpyrifos and other cholinesterase-inhibiting organophosphate pesticides. Fellowship - Environmental Estrogens, Breast Cancer Therapeutics,
and the Estrogen Receptor (ER): Characterization of the Diverse
Ligand Binding Properties of the ER The goal of this project is to understand, on a molecular level, how the ER binds environmental estrogens, estrogens and antiestrogens. A structural understanding of how these compounds interact with the ER and elicit different responses will assist in identifying estrogenic activity in compounds before they are introduced into the environment, as well as in identifying compounds with potential therapeutic benefit for treating breast cancer. WHAT OTHER POTENTIAL EFFECTS CAN RESULT FROM PESTICIDE EXPOSURE? Anti-androgenic Pesticides: Impact on Male Reproduction
The objective of the proposed research is to determine immediate and long-term reproductive sequelae following gestational plus lactational exposures to two anti-androgenic pesticides, individually and in combination. Rabbits were chosen as animal model for studies proposed in this application because the infantile period in this species is relatively long. The overall hypothesis to be tested is that exposure to endocrine-disrupting pesticides (p,p'-DDT and vinclozolin) even at low concentrations, during differentiation of the reproductive system alters reproductive function as adults. Mechanisms of Carcinogenesis of the Fungicide and Rat Bladder
Carcinogen o-Phenylphenol Ortho-phenylphenol (OPP) and its sodium salt, sodium ortho- phenylphenate (SOPP) are widely used broad spectrum fungicides and antibacterial agents. The overall objective of this program is to elucidate critical mechanisms in OPP-induced bladder carcinogenesis by (1) identifying early biochemical and genetic biomarkers relevant to rat bladder carcinogenesis, (2) determining the dose-response relationship between biomarkers and carcinogenesis, (3) studying mechanisms of reactive species generation from the primary OPP metabolite, henylhydroquinone (PHQ), and (4) determining the mechanisms underlying the sex and species differences of OPP-induced bladder cancer. Vascular Enzyme (semicarbazide-Sensitive Amine Oxidase) Mediated
Methylamine Toxicity The goal of this research is to determine the nature of enzyme-mediated vascular injury resulting from exposure to the environmental toxin methylamine. Estimating Human Health Risk from Dermal Exposure to Contaminated
Soils The primary objective is to determine the mechanism(s) of chemical transfer from soil to skin for a group of relevant environmental pollutants with varied properties, especially vapor pressure. This information will be essential to the second and third objectives, which are to develop equations relating the rate and extent of chemical release from soil to known or estimatable parameters such as vapor pressure, Henry's constants, melting point, water solubility, and lipophilicity. The final objective is to experimentally test if information about soil-to-skin transfer combined mathematically with information on chemical transfer across skin can produce reasonable estimates of dermal absorption. HOW CAN WE REDUCE DIETARY EXPOSURE TO PESTICIDES? 1998 Progress Report: Communicating Strategies for Grocery Consumers
to Reduce Their Dietary Exposure to Chemical Residues While Maintaining
a Healthy Diet We conducted eight focus groups (two with each group: African Americans,
Anglos, Publication/Presentations: "Usability Issues in Kiosk Design" By Don Zimmerman, Michel Muraski, Michael Slater, Pat Kendall, Jennifer Williams. Poster Session. June 1998, Usability Professionals Association International Conference, Washington, D.C. OTHER RESEARCH/INFORMATION ON PESTICIDES AND HUMAN HEALTH Research on the exposure and effects of pesticides on human health is being conducted in other EPA laboratories as noted below: ORD's National Exposure Research Laboratory ORD's National Health and Environmental Effects Laboratory ORD's National Center for Environmental Assessment EPA's Office of Children's Health Protection Physicians for Social Responsibility
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