2-methylaminoethanol

Endpoint summary

Description of key information

Based on physico-chemical properties and on the effects observed in animal studies, absorption of methylaminoethanol into the body is favoured via all exposure routes. MMEA produced clinical signs pointing to its well systemic availability. Due to MW of 75.1, negative logPow (-0.91), high water solubility (1000 g/L), and pronounced clinical signs observed in animals treated orally, oral absorption is considered to be extensive and therefore set to 100 %. For the purposes of hazard assessment (DNEL derivation) 50 % oral absorption is taken in case of oral-to-inhalation extrapolation (worst case). According to the criteria outlined in Guidance on Toxicokinetics (Chapter R.7C), absorption by inhalation is considered to be low due to the vapour pressure of 201 Pa (< 500 Pa), high water solubility and negative logPow (the substance may be retained in the mucus). However, 100 % absorption by inhalation (worst-case) is taken for hazard assessment due to the absence substance-specific experimental data. Dermal absorption is considered to be low. MW of 75.1 (< 100) favours dermal uptake while negative logPow and high water solubility do not. For oral-to-dermal extrapolation, dermal absorption is set to equal to oral absorption (100 %, worst case).

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

In the “Toxicological Summary for Dimethylethanolamine and Selected Salts and Esters” (2002), several studies performed with MMEA, regarding different aspects, presented.

 

MMEA as a possible inhibitor of ethanolamine and choline uptake

 

Zahniser et al. (1978) reported a teratology study where pregnant dams were exposed to one of four diets (choline-deficient, choline deficient supplemented with 0.8 % choline, choline-deficient supplemented with 1.0 % monomethylethanolamine, or choline-deficient supplemented with 1 % DMAE) beginning on gestation day six through 15 days post-partum. Monomethylethanolamine-supplementation resulted in elevated levels of both choline (43 %) and acetylcholine (27 %) when compared to levels detected in the choline-deficient derived pups. However, when looking specifically at the cortical and striatal levels of acetylcholine, the monomethylethanolamine-treated group was not different from the choline-deficient pups. Measurable (11.7 ± 1.8 nmol/g) amounts of DMAE were detected in the brains of monomethylethanolamine-exposed pups (one-day-old). DMAE was undetectable in the choline deficient or choline-supplemented pups. Significant differences were observed in the relative content of individual phospholipid in the brains. Sphingomyelin and phosphatidic acids were lower in the brains from pups on the choline-deficient diets. In the monomethylethanolamine-supplemented pups, phosphatidylcholine and phosphatidyl aminoethanol levels in the brain were significantly (p < 0.05) lower relative to the choline-deficient-fed pups Upon histopathological examination, pups from the monomethylethanolamine group showed a moderate degree of glycogen and fatty infiltrations in their livers (Zahniser et al., 1978).

In another report, addition of DMAE or monomethylethanolamine to cultured hepatocytes isolated from choline-deficient rats resulted in the biosynthesis of phosphatidyldimethylethanolamine or phosphatidyl-monomethylethanolamine in the place of phosphatidylcholine. Phosphatidyldimethylethanolamine corrected, to a limited extent, the choline-deficient reduction in VLDL secretion; however, phosphatidyl-monomethylethanolamine inhibited VLDL secretion entirely. Supplementation of these cultured hepatocytes with ethanolamine failed to improve VLDL secretion. Overall, the results suggested that the choline head-group moiety of phosphatidylcholine is specifically required for normal VLDL secretion (Yao and Vance, 1989). Without VLDL secretion, fat and cholesterol accumulate in the liver, producing liver damage (Oregon State University, 2000).Choline deficiency results in the depletion of intracellular methyl-folate and methionine with a simultaneous increase in intracellular S-adenosylhomocysteine and homocysteine concentrations (Zeisel, 2000). In an in vitro hamster perfusion study, McMaster et al. (1992) found that the presence of 0.5mM monomethylethanolamine in the perfusate significantly inhibited the uptake of radiolabelled ethanolamine. Further analysis indicated that the radioactivity associated with the ethanolamine fraction was not significantly different; however, the radioactivity associated with the phosphoethanolamine and cytidine diphosphate ethanolamine were decreased to 33 % and 63 %, respectively, relative to control values. The authors suggest that monomethylethanolamine not only inhibited the uptake of ethanolamine, but also inhibited the activity of ethanolamine kinase.

 

MMEA as a modulator of cell cycle progression and DNA synthesis in vitro

LM fibroblasts grown in the presence of monomethylethanolamine resulted in fewer and less invasive lung metastases (42 %) if injected in the nude mouse than LM fibroblasts grown in serum- or choline supplemented serum (74 % and 68 %, respectively), possibly due to modifications of surface membrane components (Kier et al., 1988).The tumors had significantly reduced activities in several mitochondrial enzymes:(Na+ K+)-ATPase, NADH-dependent cytochrome-c reductase, rotenone-insensitive NADH-dependent cytochrome-c-reductase, and rotenone-sensitive NADH-dependent cytochrome-c-reductase, relative to choline-supplemented serum. The metastases of these tumors produced only embolus formation without invasion of local tissues. Significant changes were observed in the fatty acid composition of plasma membranes, microsomes, and mitochondria with significant increases in saturated fatty acids of 16 and 18 carbons in length in the microsomes and mitochondria, accompanied by significant reductions were found in the 18 carbon-length unsaturated fatty acids. Monomethylethanolamine-supplemented serum produced a significant reduction in the ratios of unsaturated : saturated and long chain (>18 carbons):short chain (<18 carbons) fatty acids (Kier and Schroeder, 1982; Kier et al., 1988).

 

In another in vitro study, the addition of 1 mM monomethylethanolamine to NIH 3T3 cells produced a ten-fold increase in DNA synthesis. The combination of monomethylethanolamine (1 mM) and insulin (500 nM) increased insulin-induced DNA synthesis by almost six-fold. Furthermore, the addition of choline (1 or 5 mM) further enhanced the combined effects of monomethylethanolamine and insulin without potentiating the mitogenic effects of monomethylethanolamine alone. Inhibitors of protein kinase C (GF 109203 X or staurosporine) enhanced the combined effect of monoethanolamine and insulin, causing the authors to speculate that the signal transduction pathway induced by these chemicals is inhibited by protein kinase C (Kiss and Crilly, 1996; Kiss et al., 1996).

Exposure of Friend leukemia cells to monomethylethanolamine at 10 μg/mL, either prior to or simultaneously with dimethylsulfoxide, inhibited dimethylsulfoxide-induced differentiation. Changes in the phospholipid composition suggest that inhibition of cell differentiation may be attributed to modification of phospholipid composition of the cell membrane (Kaiho and Mizuno, 1985).