May 17, 2010 — In a representative sample of US children, those with higher levels of organophosphate pesticide metabolites in their urine were more likely to have attention-deficit/hyperactivity disorder (ADHD) than children with lower levels, indicating less exposure to these compounds, researchers report in the June issue of Pediatrics, published online May 17.
"Each 10-fold increase in urinary concentration of organophosphate metabolites was associated with a 55% to 72% increase in the odds of ADHD," first study author Maryse F. Bouchard, PhD, of the Department of Environmental and Occupational Health, University of Montreal, Quebec, Canada, told Medscape Psychiatry.
Previous similar investigations, Dr. Bouchard noted, have focused on "special groups with high levels of exposure, such as children from agricultural communities, and reported pesticides-related cognitive deficits (involving memory and attention), and behavioral problems. The present study is the first investigation on children's neurodevelopment to be conducted in a group with no particular pesticide exposure."
Michael L. Goldstein, MD, who was not involved in the study, said the study results are "very interesting findings from a very well-done study from a good database." The report, he said, "certainly got my attention when I read it; I was really impressed by it. I think it is a groundbreaking study, added Dr. Goldstein, a specialist in child neurology with Western Neurological Associates in Salt Lake City, Utah, and a faculty member of the American Academy of Neurology.
The findings are based on cross-sectional data on 1139 children, aged 8 to 15 years, from the National Health and Nutrition Examination Survey (2000-2004). One hundred nineteen of the children met current diagnostic criteria for ADHD. When children taking ADHD medication were included as case subjects, there were 148 cases.
Six urinary dialkyl phosphate (DAP) metabolites, resulting from the degradation of different organophosphates, were measured in urine to provide an indicator of the body burden of common organophosphates. The proportions of children with urinary DAP concentrations below the detection limit were between 35.7% and 80.0%. Most children (93.8%) had one or more detectable metabolites of the 6 DAPs measured. Sex, race/ethnicity, and fasting duration were not significantly associated with DAP metabolite concentrations (all P > .3).
For the most commonly detected pesticide metabolite, dimethyl thiophosphate (64.3%), those with levels higher than the median of detectable concentrations had nearly twice the odds of ADHD (adjusted odds ratio [OR], 1.93; 95% confidence interval [CI], 1.23 – 3.02) compared with children with undetectable levels. The adjusted OR was higher when children taking ADHD medication were included as case subjects (adjusted OR, 2.12; 95% CI, 1.32 – 3.43).
Link Makes Biologic Sense
Several biological mechanisms might underlie an association between organophosphate pesticides and ADHD.
"It is very well established that organophosphates disrupt brain neurochemical activity. Indeed, their efficacy as pesticides result from their toxic effect on the central nervous system of insects," Dr. Bouchard noted.
"In particular, organophosphates disrupt the activity of acetylcholine, a neurotransmitter also implicated in ADHD. In addition, certain organophosphates affect growth factors, several neurotransmitter systems, and second messenger systems. These changes in brain activity could well result in ADHD-like symptoms," she said.
Dr. Goldstein said the data on organophosphate pesticides and ADHD "look like the data we saw 30 to 40 years ago with lead exposure, and it may turn out to be the same thing — that even small exposures (to organophosphate pesticides) are very harmful to kids."
Need for Replication of Results
The current study, Dr. Bouchard's team points out, had several limitations — the most important one being the use of only 1 spot urine sample to assess organophosphate exposure.
"Given the cross-sectional nature of our analysis, we cannot rule out the possibility that children with ADHD engage in behaviors that expose them to higher levels of organophosphates," they write.
However, given that DAPs are eliminated from the body after 3 to 6 days, their detection in the urine of most children studied indicates continuing exposure.
Approximately 40 organophosphate pesticides are registered with the US Environmental Protection Agency (EPA), the investigators note in their report. In 2001, 73 million pounds of organophosphates were used in both agricultural and residential settings. Diet is a major source of pesticide exposure for children. According to a 2008 US report, detectable concentrations of the organophosphate malathion were found in 28% of frozen blueberry samples, 25% of strawberry samples, and 19% of celery samples.
"This is the first study to link exposure to pesticides at levels common in the general population with adverse health effects," said Dr. Bouchard. "These findings should be replicated before strong conclusion can be made. However, it seems prudent to reduce pesticides exposure by reducing their use in agriculture."
In a written statement to Medscape Psychiatry, CropLife America, an industry group representing the developers, manufacturers, formulators, and distributors of plant science solutions for agriculture and pest management in the United States, said their review of the study "leads us to believe much more research is needed to ascertain if there is a direct link between exposure to organophosphate pesticides and the development of ADHD in children.
"All crop protection products are extensively reviewed by regulatory agencies before approval for market use. Many scientific factors are examined by government pesticide regulators, based on extensive laboratory testing, all of which are intended to guarantee safety for the environment and people, including children," the statement reads. "The class of crop protection compound that is the subject of this study has been approved and registered by the US EPA, and when used according to the label, the EPA has determined it to be safe."
The study was supported by a grant from the National Institute of Environmental Health Sciences. The study authors and Dr. Goldstein have disclosed no relevant financial relationships.
Pediatrics. Published online May 17, 2010.
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