Tuesday, December 23, 2008

Diethanolamine Inhibits Brain Development When Applied to the Skin

Brooklyn Dodger(s) comments: DEA ought to be a 2B carcinogen, by skin application, although it's not, for reasons to be discussed in another post. The Dodger(s) interest in DEA relates to its presence in MWF's. But the heat around DEA which fuels mechanistic research is generated by the presence of DEA as an unwanted impurity in skin lotion. One theory is that liver damage and liver cancer in mice follow from choline depletion. Here we have an investigation of developmental disability from DEA applied to the skin.

The effect level in this study is 80 mg/kg/day for 10 days, with 60 mg/kg as a NOEL. The Dodger(s) will context this with the NTP bioassay in another post. So the uncertainty factors of 10 for acute to chronic, 10 for animal to human, and 10 for population variability would generate a RfD of 60 ug/kg/day as a default. [But, is 10 days acute or chronic? the fetus is sensitive for only 10 days or maybe only 1 day within the 10. but there's an effect at 60 mg/kg, just not significant. so maybe the real NOEL is 40]

Now comes a skin lotion, with 1.8 ppm DEA, likely an impurity in a diethanolamide-fatty acid condensate. [Still dirty after all these years?]. The 3 women dosed had plasma levels varying by 3-fold from top to bottom, with 5 nmoles/ml about the mean, compared to 1250 in the 80 mg/kg mice. A ratio of about 250 from the effect level. The Dodger(s) think this is too close.

Hazcomers take note.


Dose Response Effects of Dermally applied Diethanolamine on Neurogenesis in Fetal Mouse Hippocampus and Potential Exposure of Humans

Corneliu N. Craciunescu, Mihai D. Niculescu, Zhong Guo, Amy R. Johnson, Leslie Fischer, and Steven H. Zeisel

Toxicol. Sci. 2009 107: 220-226;


"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/day of DEA during pregnancy in mice reduced neurogenesis and increased apoptosis in the fetal hippocampus. ... 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 ... Also, this dose of DEA to dams increased rates of apoptosis in E17 fetal hippocampus ... 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 dimethyldiethanolamine, [BrooklynDodger(s) comment: risk assessment conclusion implied but not justified] but these were far below those concentrations associated with perturbed brain development in the mouse."

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