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EC number: 203-710-0
CAS number: 109-83-1
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).
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).
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