Council on Environmental Health
Article Review

Prepared by: Catherine J. Karr, MD, PhD
June 2010

TITLE
Attention-Deficit/Hyperactivity Disorder and Urinary Metabolites of Organophosphate Pesticides

AUTHORS
Maryse F. Bouchard, David C Bellinger, Robert O. Wright, Marc G. Weisskopf

REFERENCE
Pediatrics 2010;125;1270-1277

STUDY TYPE
Population based, cross –sectional epidemiological study

BACKGROUND
Organophosphate insecticides are widely used in U.S. agricultural production. Dietary exposures to residues on food products are felt to be the most important source of exposure for most infants and children. Experimental studies have identified several mechanisms of neurodevelopmental toxicity for these compounds including disruption of growth factors, neurotransmitters systems and second-messenger systems. In animal studies, exposure to these compounds has been shown to cause hyperactivity and cognitive deficits.  Emerging epidemiological studies of children in settings with relatively high exposures have observed associations between early life exposure and increased risk of behavioral and cognitive problems. These studies were done in agricultural settings with farmworker children or with children in inner city housing with routine residential pesticide treatment.

METHODS
The authors took advantage of existing data from the 2000-2004 National Health and Nutrition Examination Survey (NHANES), a population based health survey of non-institutionalized US residents conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. Cross sectional data were available for 1139 children aged 8-15 years who were examined for responses to a structured interview with a parent to ascertain ADHD diagnosis status as well as “spot” urinary concentrations of the 6 organophosphate insecticide metabolites (dialkyl phosphates, DAPs). Total DAP urinary concentrations and a sum of the metabolites representing differing chemical structures of the parent compounds - diethyl alkyl phosphate metabolites (DEAPs) and dimethyl alkyl phosphates (DMAPs) were evaluated. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals for ADHD per 10 fold increases in total DAPs, DEAPs, DMAPs with adjustment for gender, age, race/ethnicity, poverty/income ratio (PIR), fasting duration, and urinary creatinine concentration.

RESULTS
One hundred nineteen children met the diagnostic criteria for ADHD (population prevalence 12.1%, 95% CI 9.6%-15.1%). Most children had ≥ 1 of the six possible metabolites in a detectable concentration. Higher DAP concentrations were associated with higher creatinine concentrations, younger age, lower blood lead concentrations and higher PIR. Gender, race/ethnicity, and fasting duration were not significantly associated with DAP metabolite concentrations.

Children with higher urinary alkyl phosphate concentrations were more likely to be diagnosed as having ADHD. This association was driven by the DMAP metabolites (ORadj 1.55, 95% CI 1.14-2.10). Analysis of ADHD subtypes found a higher magnitude of risk associated with DMAP metabolites and the hyperactive/impulsive subtype (OR 2.13; 95% CI 1.08-4.20). For the most commonly detected DMAP metabolite, dimethylthiophosphate, children with levels higher than the median of detectable concentrations had twice the odds of ADHD (OR 1.93, 95% CI 1.23-3.02).

CONCLUSIONS
This study of a representative sample of U.S. children aged 8-15 years old showed that children with higher urinary levels of organophosphate metabolites were more likely to meet the diagnostic criteria for ADHD. The strengths of the study were the large sample size, the exposures within ranges encountered by the general population of children in the U.S., and the well defined outcome (case definition for ADHD). The primary limitations are the cross sectional nature of the data and the inability in these data to address ADHD risk factors which may be potential confounders such as parental psychopathology and parenting behavior. Such confounding could bias the findings toward or away from the null, depending on the relationship of these factors with pesticides.  The design, assumes that the concurrent exposure assessment is a good surrogate for exposure during critical developmental windows that influence development and presentation of ADHD. The potential misclassification of exposure that this presents is expected to be non-differential and would serve to bias the effect estimates toward the null.

THE BOTTOM LINE
Organophosphate insecticide exposure among children is widespread, largely from the use of these chemicals in conventional agricultural production. The potential neurodevelopmental toxicity of low level chronic exposures is increasingly appreciated in experimental studies. This study adds to a complementary and accumulating epidemiological evidence base that chronic exposures occurring in children in the U.S. today may have adverse consequences on behavior.

PUBLIC HEALTH POLICY & PEDIATRIC PRACTICE IMPLICATIONS
In 1999-2000, largely based on concerns for child health, the US EPA began a phase out of non-agricultural uses of two of the most common organophosphates available for residential pest control (in home or garden) – chlorpyrifos and diazinon.  The impact was observed coincidentally in a longitudinal cohort study where structural pest control with these agents was common. Levels of chlorpyrifos in plasma blood levels decreased more than fivefold among women and infants participating in the study. Today, most organophosphate exposure occurs through ongoing use in food production. Studies have documented that children’s exposure to these pesticides can be reduced by changing from a conventional diet to an organic foods based diet. Some types of foods are more likely to contain residues of these pesticides than others. Washing and peeling may reduce the residue on some fruits and vegetables.

Pediatric care providers should be aware of pest control practices in the homes and other important settings (schools, daycares) of their patients. Providers play an important role in promoting least toxic approaches to pest control and improved accessibility of affordable organic foods.

RELATED RESOURCES

  • Rauh et al. Impact of Prenatal Chlorpyrifos Exposure on Neurodevelopment in the First 3 Years of Life Among Inner-City Children. Pediatrics 2006;118: e1845-e1859
  • Karr C, Solomon GM, Brock-Utne A. Health Effects of Common Home, Lawn and Garden Pesticides. Pediatr Clin North Am. 2007;54:63-80.
  • Environmental Working Group Food Shopper’s Guide to Pesticides http://www.foodnews.org/
  • Lu C, Toepel K, Irish R, et al. Organic diets significantly lower children’s dietary exposure to organophosphorus pesticides. Environ Health Perspect 2006; 114:260–3.

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