Prenatal Exposure to Insecticide Chlorpyrifos Linked to Alterations in Brain Structure and Cognition

Even low to moderate levels of exposure to the insecticide chlorpyrifos during pregnancy may lead to long-term, potentially irreversible changes in the brain structure of the child, according to a new brain imaging study by researchers from the Columbia Center for Children's Environmental Health at the Mailman School of Public Health, Duke University Medical Center, Emory University, and the New York State Psychiatric Institute. The changes in brain structure are consistent with cognitive deficits found in children exposed to this chemical.

Results of the study appear online in the April 30 PNAS.

 

Main Effects of CPF Exposure on Brain Surface Measures

The new study is the first to use MRI to identify the structural evidence for these cognitive deficits in humans,confirming earlier findings in animals. Changes were visible across the surface of the brain, with abnormal enlargement of some areas and thinning in others. The disturbances in brain structure are consistent with the IQ deficits previously reported in the children with high exposure levels of chlorpyrifos, or CPF, suggesting a link between prenatal exposure to CPF and deficits in IQ and working memory at age 7.

The study also reports evidence that CPF may eliminate or reverse the male-female differences that are ordinarily present in the brain. Further study is needed to determine the consequences of these changes before and after puberty, the researchers say.

Notably, the brain abnormalities appeared to occur at exposure levels below the current EPA threshold for toxicity, which is based on exposures high enough to inhibit the action of the key neurological enzyme cholinesterase. The present findings suggest that the mechanism underlying structural changes in the brain may involve other pathways.

According to the lead author, Virginia Rauh, ScD, Professor at the Mailman School of Public Health and Deputy Director of the Columbia Center for Children's Environmental Health, "By measuring a biomarker of CPF exposure during pregnancy, and following the children prospectively from birth into middle childhood, the present study provides evidence that the prenatal period is a vulnerable time for the developing child, and that toxic exposure during this critical period can have far-reaching effects on brain development and behavioral functioning."

"By combining brain imaging and community-based research, we now have much stronger evidence linking exposure to chlorpyrifos with neurodevelopmental problems," adds senior author Bradley S. Peterson, MD, Chief of Child & Adolescent Psychiatry, New York State Psychiatric Institute, and Director of MRI Research in the Department of Psychiatry, Columbia University Medical Center.

In the current study, the researchers used MRI to evaluate the brains of 40 New York City children, ages 5 to 11, whose mothers were enrolled prenatally in a larger cohort study. Researchers compared 20 children with high exposures to CPF with 20 children with lower exposures; all exposures occurred prior to the EPA ban on household use of the chemical in 2001. They found brain anomalies were associated with the higher exposure.

Since the 2001 ban, a drop in residential exposure levels of CPF has been documented by Robin Whyatt, DrPH, a co-author on the present study and Professor of Clinical Environmental Health Sciences and Co-Deputy Director of the Columbia Center for Children's Environmental Health at the Mailman School. However, the chemical continues to be present in the environment through its widespread use in agriculture (food and feed crops), wood treatments, and public spaces such as golf courses, some parks, and highway medians. People near these sources can be exposed by inhaling the chemical, which drifts on the wind. Low-level exposure can also occur by eating fruits and vegetables that have been sprayed. Although the chemical is degraded rapidly by water and sunlight outdoors, it has been detected by the Columbia researchers in many urban residences years after the ban went into effect.

The study was supported by the National Institute of Environmental Health Sciences Grants 5P01ES09600, P50ES015905, and 5R01ES08977, as well as pilot funding through ES009089; EPA STAR Grants RD834509, RD832141, and R827027; National Institute of Mental Health Grants MH068318 and K02-74677; and the John and Wendy Neu Family Foundation.

Additional co-authors included Frederica P. Perera and Megan K. Horton, Mailman School; Ravi Bansal, Xuejun Hao, and Jun Liu, Columbia University Medical Center; Dana Boyd Barr, Emory University; and Theodore A. Slotkin, Duke University