Pentasodium (carboxylatomethyl)iminobis(ethylenenitrilo)tetraacetate

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

other information

Study period:

2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published data, information on methods and results is sufficient to make an assessment.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Alleviation of the two-cell block of ICR mouse embryos by polyaminocarboxylate metal chelators

Author:

Matsukawa, T.

Year:

2002

Bibliographic source:

65-71. [Reproduction (Cambridge, England)]

Materials and methods

Type of study / information:

Alleviation of the two-cell block of ICR mouse embryos by polyaminocarboxylate metal chelators

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

None specified

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)

EC Number:

200-652-8

EC Name:

N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)

Cas Number:

67-43-6

IUPAC Name:

N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine

Details on test material:

- Name of test material (as cited in study report): Diethylenetriaminepentaacetate (DTPA)

Results and discussion

Any other information on results incl. tables

The order of stability constants of polyaminocarboxylates for transitionmetal ions such as zinc, copper and iron isas follows: NTA EDDA < EGTA < EDTA < DTPA. Addition of 10 or 100 µmol polyaminocarboxylates 1^-1 to the medium significantly enhanced the development of most one-cell embryos (66-88%) beyond thetwo-cell stage compared with that(<25%) in medium without polyamino­carboxylates. Although EDDA, EDTA and DTPA at 10 µmol1^-1induced the development of most one-cell embryos to the four-cell stage and beyond, a higher concentration (100 µmol 1^-1) of NTA and EGTA was required to obtain a similar result. Therefore, the ability of polyaminocarboxylates to overcome the two-cell block is not correlated with their potency to chelate transition metal ions. In contrast, the non-polyaminocarboxylatesdipicolinic acid and deferoxamine, at 10 and 100µmol I^-1,did not have the same effect. Taken together, the results indicate that the ability of polyaminocarboxylates to overcome the two-cell block in embryo development is due to some common feature or features other than the ability to chelate transition metal ions.

 

Applicant's summary and conclusion

Conclusions:

The present study demonstrated that polyaminocarboxylates with different stability constants for transition metal ions have an ability to alleviate the two-cell block in ICR mouse zygotes; however, this ability was not necessarily correlated with the stability constants of the polyaminocarboxylates. Accordingly, although it remains to be clarified how EDTA and other polyaminocarboxylates alleviate the two-cell block in ICR mouse embryos, it seems likely that some common structural feature of polyaminocarboxylates, other than their ability to chelate metal ions, is required to promote embryonic development, especially beyond the second cell cycle division.