Diethanolamine alters neurogenesis and induces apoptosis in fetal mouse hippocampus

Abstract

Diethanolamine (DEA) is present in many consumer products such as shampoo. Dermal administration of DEA diminishes hepatic stores of the essential nutrient choline, and we previously reported that dietary choline deficiency during pregnancy reduces neurogenesis and increases apoptosis in the hippocampus of fetal rats and mice. Therefore, DEA could also alter brain development. Timed-pregnant C57BL/6 mice were dosed dermally from gestation day 7 through 17 with DEA at 0, 20, 80, 160, 320, and 640 mg/kg body/day. At doses of DEA > 80 mg/kg body/day, we observed decreased litter size. In fetuses (embryonic day 17) collected from dams treated dermally with 80 mg/kg body/day DEA, we observed decreased neural progenitor cell mitosis at the ventricular surface of the ventricular zone of the hippocampus [to 56+/-14% (se) histone 3 (H3) phosphorylation as compared to controls; P < 0.01]. We also observed increased apoptosis in fetal hippocampus (to 170+/-10% of control measured using TUNEL and to 178+/-7% of control measured using activated caspase 3; P < 0.01). Thus, maternal exposure to DEA reduces the number of neural progenitor cells in hippocampus by two mechanisms, and this could permanently alter memory function in offspring of mothers exposed to this common ingredient of shampoos and soaps.

Umbilical choline and related methylamines betaine and dimethylglycine in relation to birth weight

“…Variation in maternal choline status could possibly influence fetal outcome through disturbances in cell membrane synthesis, increase in homocysteine concentrations, and/or perturbation of methylation reactions and changes in acetylcholine production. Choline also influences stem cell proliferation, apoptosis in the brain, and the developing hippocampus (memory center) in rodents (9). Maternal choline supplementation in rats during critical periods in pregnancy causes lifelong changes in brain structure (10).…”

DEA in consumer products is safe

“…The paper by Craciunescu et al . reporting altered neurogenesis and apoptosis in fetal mouse hippocampus following diethanolamine (DEA) exposure in utero (1) grossly overestimates potential human exposure to DEA from personal care products and implies a risk from their use that is not supported by the data.…”

“…The paper by Craciunescu et al . provides exposure estimates of 8–200 mg/kg/day from daily use of shampoo (1). In fact, using the values above to calculate the amount of DEA that would be absorbed from daily use of shampoo results in a very different conclusion.…”

“…This value can then be compared to the 20 mg/kg/ day no‐effect level in mice reported in Craciunescu et al . (1) to demonstrate a safety factor well in excess of 1000 for DEA exposure from shampoo. The use of additional DEA‐containing products would be expected to contribute equally small amounts of DEA, and a wide margin of safety would still exist.…”

“…The use of additional DEA‐containing products would be expected to contribute equally small amounts of DEA, and a wide margin of safety would still exist. Further, the hypothesized mechanism behind the adverse developmental effects reported by Craciunescu et al is choline deficiency (1), to which humans are believed to be less susceptible than rodents (7–9), thereby increasing the safety factor further. Thus the inference that the use of consumer products containing DEA by pregnant women may present a risk to the unborn is without merit and not supported by the data.…”