Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not reported, published 2002
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference Type:

Materials and methods

Test guideline
no guideline required
Principles of method if other than guideline:
basic research
GLP compliance:
not specified
Type of method:
in vitro

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
not reported (publication is a short review)

Test animals

other: embryos

Administration / exposure

Route of administration:
other: in vitro
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
1. 10 h in embryo culture for studies of 14C-labeled choline uptake in betaine, phosphocholine, phosphatidylcholine (PtdCho), and sphingomyelin.
2. 24 h in embryo culture for study of diacylglycerol and ceramide
Frequency of treatment:
not applicable
Duration of test:
single application
Doses / concentrations
Doses / Concentrations: 375 µM
Basis: nominal conc.
No. of animals per sex per dose:
not applicable
Control animals:
other: untreated embryos

Results and discussion

Effect levels

Dose descriptor:
other: mechanism of developmental toxicity
Basis for effect level:
other: DMAE is an inhibitor of choline uptake
Remarks on result:
not measured/tested
Effect level not specified

Observed effects

see "Remarks on results"

Any other information on results incl. tables

1.After 10 h of embryo culture with 375 µM DMAE, free 14C-choline in the embryo was reduced by 60%; in both embryos and yolk sacs, incorporation of 14C-choline into phosphocholine, PtdCho, and sphingomyelin was decreased to 25%, 35% and 50% of control values, respectively. In DMAE-treated embryos, labeled betaine was threefold higher than in controls. In embryos and yolk sacs, treatment with DMAE resulted in reduced phosphatidylethanolamine (PtdEtn) synthesized from 3H-ethanolamine.

2. Treatment with DMAE resulted in a 15% increase of embryonic ceramide.

Applicant's summary and conclusion

Altered levels of diacylglycerol and ceramide were observed in inhibitor-treated embryos
Executive summary:

" The purpose of this research was to study choline metabolism in gastrulation/neurulation stage mouse embryos and to identify potential biochemical mechanisms associated with growth and developmental abnormalities previously shown to be caused by an inhibitor of choline uptake, 2-dimethylaminoethanol (DMAE)..." Treatment with DMAE affected accumulation of 14C-labeled choline, betaine, phosphocholine, PtdCho, and sphingomyelin. The levels of diacylglycerol and ceramide were also altered in inhibitor-treated embryos.

The present study suggests that reduced PtdCho availability caused by decreased choline transport and/or inhibition of PtdCho synthesis through the CDP-choline pathway (drawn in the original paper) could be responsible for the increased cell death and craniofacial and neural tube defects in neurulation stage mouse embryos grown in culture (results of a previous study cited in the present paper).

"DMAE is a competitive inhibitor of choline uptake and transport and an inhibitor of choline kinase. DMAE caused a reduction in PtdEtn synthesis, reflecting that besides being a choline analog, it is structurally related to ethanolamine. Further investigation into the effect of DMAE on ethanolamine metabolism is necessary to understand the full impact of DMAE on embryonic development."

" The potential teratogenic effects of DMAE are of special concern as it is currently sold as a nutrient supplement that claims to enhance acetylcholine-related functions such as memory and learning. A related molecule found in many commercial products, diethanolamine, has been shown to disrupt choline metabolism and cause tumor formation in mice. Consequently, further investigation into the effects of reduced choline availability and abnormal choline metabolism in the mother and the developing conceptus is warranted"

This in vitro experiment is considered to be of little significance because the conditions does not reflect the situation as it occurs in animals and humans to a limited extent. Therefore these results are judged only very careful. The actual animal GLP guideline studies are considered to be most reliable and provide valuable insights which allow judging the hazard profile of DMAE.