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Theodore A. Slotkin, Ph.D. Background: There is a growing body of evidence that suggests that exposure to environmental agents in utero or very early after birth can have life-long effects. This phenomenon is referred to as the fetal basis of adult disease. It is of growing concern to NIEHS and environmental health scientists worldwide. Hypertension, diabetes, asthma, and cardiovascular diseases are but a few of the illnesses that have been suggested as possible effects from these early-life exposures. This investigator examined the combined exposures of terbutaline, a drug used to arrest preterm labor, and subsequent exposure to the organophosphate pesticide chlorpyrifos on several indices of brain cell growth and function. Advance: Young rats were given terbutaline on days 2-5 after birth, followed by chlorpyrifos on days 11-14. Neither treatment affected growth or viability of the young rats; however, both elicited alterations in brain cell differentiation and cholinergic innervation at day 15 persisting into adulthood (day 60). Biomarkers of brain cell number, cell size, and neuritic projections were affected by either agent alone; however the combined exposure produced more severe effects. Implication: These findings suggest that terbutaline is a developmental neurotoxicant much like chloripyrifos. The authors conclude that the use of terbutaline to prevent preterm labor may be creating a subpopulation that is more sensitive to the adverse neural effects of organophosphate pesticides. Further studies are needed to repeat these findings, but if the results are confirmed, use of these compounds may need additional scrutiny. Citation: Rhodes MC, Seidler FJ, Qiao D, Tate CA, Cousins MM, Slotkin TA. Does pharmacotherapy for preterm labor sensitize the developing brain to environmental neurotoxicants? Cellular and synaptic effects of sequential exposure to terbutaline and chlorpyrifos in neonatal rats. Toxicol Appl Pharmacol. 2004 Mar 1; 195(2):203-17. |
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