Biomarkers and Neurobehavioral Effects of Perinatal Exposure to Chlorpyrifos and Other Organophosphate Insecticides

EPA Grant Number: R828611
Title: Biomarkers and Neurobehavioral Effects of Perinatal Exposure to Chlorpyrifos and Other Organophosphate Insecticides
Investigators: Wilkins, John R. , Dietrich, Kim , Jacobson, Sandra , Lindsay, Ronald L. , Moeschberger, Melvin L. , Nishioka, M. , Weghorst, Christopher M.
Current Investigators: Wilkins, John R. , Dietrich, Kim , Moeschberger, Melvin L. , Nishioka, M. , Weghorst, Christopher M.
Institution: The Ohio State University , University of Cincinnati , Wayne State University
Current Institution: The Ohio State University , Battelle Memorial Institute , University of Cincinnati
EPA Project Officer: Laessig, Susan A.
Project Period: February 12, 2001 through February 11, 2004 (Extended to February 11, 2006)
Project Amount: $1,126,463
RFA: Biomarkers for the Assessment of Exposure and Toxicity in Children (2000) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Health

Description:

Employing BIOMARKERS of EXPOSURE and SUSCEPTIBILITY in a longitudinal design, the proposed research will evaluate the putative relationship between perinatal exposure to chlorpyrifos (CP) and other organophosphate (OP) insecticides, compounds demonstrated to be neurodevelopmental toxicants in animals, and adverse neurobehavioral effects among infants and young children. Cohort ascertainment will involve recruitment of 176 women in their second trimester of pregnancy into the longitudinal study, which will follow only healthy full-term newborns for 2 years.

Approach:

For each pregnancy, the following data will be obtained: (i) maternal exposure to CP and other OPs, (ii) maternal exposure to other neurodevelopmental toxicants likely to be factors in the target population (e.g., Pb and nicotine), (iii) maternal demographics and other potentially confounding family-based factors (e.g., SES), and (iv) relevant clinical information pertaining to the pregnancy and birth event (e.g., APGAR scores). Maternal exposures to the OPs of interest will be assessed by analyses of urine obtained from the mother prior to birth. At regular intervals throughout the follow-up period, urine samples will be collected from the infants and analyzed for dialkylphosphates and 3,5,6-trichloro-2-pyridinol (TCP). Levels of 2-isopropyl-6-methyl-4-pyrimidinoI (IMP) will also be determined. In addition, two postnatal blood samples will be obtained from the youth (one at 12 months, one at 24 months) in order to determine blood Pb levels. Blood will also be used to determine the infant's paraoxonase (PON1) genotype, a biomarker of susceptibility to OP toxicity. Because vulnerability to the adverse effects of neurodevelopmental toxicants begins shortly after conception, blood obtained from the expectant mothers will be used to determine the mother-'s PON1 genotype.

After birth, relevant data will be obtained from the mother-child dyads at 3, 12, and 24 months postnatal. At 3 months, neurobehavioral data will be obtained on the infant by administration of the Bayley Scales of Infant Development-11 (BSID-11). At 12 months, control data on potential confounders will be obtained, in addition to data on breast-feeding and parental IQ. At 24 months, the primary neurobehavioral data will be obtained by repeat administration of the BSID-11, in addition to a one-time administration of Ireton's Child Development Inventory (CDI). Multiple regression will be used to evaluate the relationship between the indicators of neurobehavioral development obtained and OP exposure.

Expected Results:

This approach to analysis of the data permits control of the potentially confounding (and interactive) effects of Pb and other factors (e.g., maternal IQ), and also allows examination of the potential influence of PON 1 genotype (of the mother andlor child) as an effect modifier.

Publications and Presentations:

Publications have been submitted on this project: View all 2 publications for this project

Supplemental Keywords:

infants, children; insecticides; biomarkers of exposure, susceptibility., RFA, Health, Scientific Discipline, Toxicology, Genetics, Health Risk Assessment, Susceptibility/Sensitive Population/Genetic Susceptibility, Biochemistry, Children's Health, genetic susceptability, Molecular Biology/Genetics, health effects, sensitive populations, infants, vulnerability, biomarkers, adolescence, health risks, chlorpyrifos, measuring childhood exposure, exposure, neurotoxicity, longitudinal study, endocrine disruptors, children, children's vulnerablity, assessment of exposure, insecticides, neurobehavioral effects, perinatanl exposure, biological markers, developmental disorders, genetic susceptibility, organophosphate pesticides, environmental hazard exposures

Relevant Websites:

Synthesis Report of Research from EPA’s Science to Achieve Results (STAR) Grant Program: Feasibility of Estimating Pesticide Exposure and Dose in Children Using Biological Measurements (PDF) (42 pp, 3.87 MB)

Progress and Final Reports:

2001 Progress Report
2002 Progress Report
2003 Progress Report
2004 Progress Report
Final Report