Potential effects of chlorpyrifos on fetal growth outcomes: implications for risk assessment

Chlorpyrifos (CPF) is one of the most widely used organophosphate insecticides in the United States. By December 2000, nearly all residential uses were voluntarily canceled, so that today, CPF is only used to control insect pests on a variety of crops. Periodic review of the potential effects of CPF on all developmental outcomes is necessary in the United States because the Food Quality Protection Act mandates special consideration of risk assessments for infants and children. This article reviews epidemiologic studies examining the association of potential CPF exposure with growth indices, including birth weight, birth length, and head circumference, and animal studies focusing on related somatic developmental endpoints. It differs from earlier reviews by including an additional cohort study and providing in-depth systematic evaluation of the patterns of association across different studies with respect to specificity of biomarkers for CPF, consistency, dose response, strength of association, temporality, and biological plausibility (Hill 1965), as well as consideration of the potential role of effect modification and bias. The review did not identify any strong associations exhibiting consistent exposure-response patterns that were observed in more than one of the four cohort studies evaluated. In addition, the animal data indicate that developmental effects occur at doses that produce substantial maternal toxicity and red blood cell (RBC) acetylcholinesterase (AChE) inhibition. Based on consideration of both the epidemiologic and animal data, maternal RBC AChE inhibition is a more sensitive endpoint for risk assessment than somatic developmental effects reviewed in this article.