ToxSci Advance Access published online on October 23, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn227
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Dose Response Effects of Dermally applied Diethanolamine on Neurogenesis in Fetal Mouse Hippocampus and Potential Exposure of Humans
1 Department of Nutrition, School of Public Health and Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461 2 Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081-4332
3 Author to whom correspondence and proofs should be addressed: Steven H. Zeisel, MD, PhD, CB#7461, 2115A Michael Hooker Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7461, Tel: (919) 843-4731; Fax: (919)-843-8555; email: steven_zeisel{at}unc.edu
Received June 9, 2008; revision received September 10, 2008; accepted October 18, 2008
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Abstract |
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Diethanolamine (DEA) is a common ingredient of personal care products. Dermal administration of DEA diminishes hepatic stores of the essential nutrient choline, and alters brain development. We previously reported that 80 mg/kg/d of DEA during pregnancy in mice reduced neurogenesis and increased apoptosis in the fetal hippocampus. This study was designed to establish the dose response relationships for this effect of DEA. Timed-pregnant C57BL/6 mouse dams were dosed dermally from gestation day 7 - 17 with DEA at 0 (controls), 5, 40, 60, and 80 mg/kg body/day. Fetuses (embryonic day 17; E17) from dams treated dermally with 80 mg/kg body/day DEA, had decreased neural progenitor cell mitosis at the ventricular surface of the ventricular zone (hippocampus, 54.1 ± 5.5%; cortex, 58.9 ± 6.8%; compared to controls; p <0.01). Also, this dose of DEA to dams increased rates of apoptosis in E17 fetal hippocampus (to 177.2 ± 21.5% of control; measured using activated caspase 3; p <0.01). This dose of DEA resulted in accumulation of DEA and its metabolites in liver and in plasma. At doses of DEA less than 80 mg/kg body/day to dams, there were no differences between treated and control groups. In a small group of human subjects, dermal treatment for 1 month with a commercially available skin lotion containing 1.8 mg DEA per gram resulted in detectable plasma concentrations of DEA and DMDEA, but these were far below those concentrations associated with perturbed brain development in the mouse.
Key Words: diethanolamine; choline; pregnancy; brain development; mouse; hippocampus.