Despite evidence from human and animal studies that clearly identifies neurotoxicity as the primary adverse endpoint; the long-term effects of repeated occupational and environmental exposures to organophosphorus pesticides (OPs) remain poorly understood. There is also a critical need to investigate the susceptibility of children and adolescents to pesticides, since the developing brain may be uniquely sensitive to the neurotoxic effects of these agents. Partnering with colleagues at Egypt's Menoufia University, we conducted a pilot study of adolescents working for the Ministry of Agriculture as pesticide applicators for the cotton crop. Building on these preliminary findings, we propose a longitudinal study to investigate the relationship between sensitive and specific biomarkers of pesticide exposure, effect and susceptibility and multiple measures of neurobehavioral function in this unique cohort over a 5 year period to assess cumulative and potentially reversible effects. Our overarching hypothesis is that the inherent plasticity of the developing adolescent brain will allow recovery from selected neurobehavioral deficits associated with short- and long-term exposures to pesticides.
Three aims address this hypothesis, expand on the successful efforts begun in the R21 project, to build research skills at Menoufia and work with the Ministry of Agriculture to identify susceptible populations and put into place appropriate measures to reduce pesticide exposure.
Aim 1 will determine the association between pesticide exposure and neurobehavioral function in a longitudinal study among adolescent cohorts with occupational (applicators) or environmental (non-applicators) exposures to test the hypothesis that neurobehavioral performance deficits associated with short-term exposure occur during the application season but that there is recovery of selected neurobehavioral functional domains after the summer spray season ends. Some deficits may persist beyond the spray season or after repeated summer spray seasons. A biologically- based exposure assessment will incorporate levels of urinary metabolites of chlorpyrifos and profenophos (OPs) and alpha-cypermethrin (pyrethroid) and functional polymorphisms in key enzymes involved in OP metabolism (CYP2B6, CYP2C19, and PON1) as modifiers of bioeffective dose.
Aim 2 will expand the research capacity at Menoufia University by establishing a Research Institute that will: (a), build epidemiologic research capacity (b) teach grant writing and research skills in shot courses held locally and through videoconferences, (c) provide mentoring and international education experiences, and (d) implement a pilot project research program. This is designed to create a competitive research culture at Menoufia University.
Aim 3 will develop a training program for the Ministry of Agriculture workers (including applicators) on ways to reduce exposure through hygiene, behavior (work practice) change and use of protective equipment, addressing both environmental (home) and occupational exposures. A randomized controlled trial design will evaluate the impact of the training program on reaction, behavior, and knowledge (learning and retention).

Public Health Relevance

There is a critical need to investigate the susceptibility of children and adolescents to repeated occupational and environmental exposures to pesticides, since the developing brain may be uniquely sensitive to the neurotoxic effects of these agents. Our overarching hypothesis is that the inherent plasticity of the developing adolescent brain will allow recovery from selected neurobehavioral deficits associated with short- and long- term exposures to pesticides. Three aims address this hypothesis, expand on the successful efforts begun in the R21 project, to build research skills at Menoufia University and work with the Egyptian Ministry of Agriculture to identify susceptible populations and put into place appropriate measures to reduce pesticide exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
4R01ES022163-04
Application #
8959626
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Kirshner, Annette G
Project Start
2013-03-04
Project End
2017-10-31
Budget Start
2015-11-01
Budget End
2016-10-31
Support Year
4
Fiscal Year
2016
Total Cost
$520,453
Indirect Cost
$49,410
Name
University of Iowa
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52246
Callahan, Catherine L; Hamad, Lamya A; Olson, James R et al. (2017) Longitudinal assessment of occupational determinants of chlorpyrifos exposure in adolescent pesticide workers in Egypt. Int J Hyg Environ Health 220:1356-1362
Ismail, Ahmed A; Bonner, Matthew R; Hendy, Olfat et al. (2017) Comparison of neurological health outcomes between two adolescent cohorts exposed to pesticides in Egypt. PLoS One 12:e0172696
Ismail, Ahmed A; Wang, Kai; Olson, James R et al. (2017) The impact of repeated organophosphorus pesticide exposure on biomarkers and neurobehavioral outcomes among adolescent pesticide applicators. J Toxicol Environ Health A 80:542-555
Rohlman, Diane S; Ismail, Ahmed A; Rasoul, Gaafar Abdel et al. (2016) A 10-month prospective study of organophosphorus pesticide exposure and neurobehavioral performance among adolescents in Egypt. Cortex 74:383-95
Voorhees, Jaymie R; Rohlman, Diane S; Lein, Pamela J et al. (2016) Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds. Front Neurosci 10:590
Tshala-Katumbay, Desire; Mwanza, Jean-Claude; Rohlman, Diane S et al. (2015) A global perspective on the influence of environmental exposures on the nervous system. Nature 527:S187-92
Singleton, Steven T; Lein, Pamela J; Dadson, Oswald A et al. (2015) Longitudinal assessment of occupational exposures to the organophosphorous insecticides chlorpyrifos and profenofos in Egyptian cotton field workers. Int J Hyg Environ Health 218:203-11
Callahan, Catherine L; Al-Batanony, Manal; Ismail, Ahmed A et al. (2014) Chlorpyrifos exposure and respiratory health among adolescent agricultural workers. Int J Environ Res Public Health 11:13117-29
Rohlman, Diane Schertler; Ismail, Ahmed A; Abdel-Rasoul, Gaafar et al. (2014) Characterizing exposures and neurobehavioral performance in Egyptian adolescent pesticide applicators. Metab Brain Dis 29:845-55
Khan, Khalid; Ismail, Ahmed A; Abdel Rasoul, Gaafar et al. (2014) Longitudinal assessment of chlorpyrifos exposure and self-reported neurological symptoms in adolescent pesticide applicators. BMJ Open 4:e004177

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