Diammonium [N,N-bis[2-[bis(carboxymethyl)amino]ethyl]glycinato(5-)]ferrate(2-)

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Limited reported study. For read-across justification refer to section 13.

Data source

Reference

Reference Type:

publication

Title:

A concerted approach to the study of the aneuploidogenic properties of two chelating agents (EDTA and NTA) in the germ and somatic cell lines of Drosophila and the mouse

Author:

Zordan M, Russo A, Costa R, Bianoc N, Beltrame C, Levis AG

Year:

1990

Bibliographic source:

Environ Mol Mutagen 15, 205-213

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Investigation of chromosome aberrations in germ and somatic cells of the mouse

GLP compliance:

no

Type of assay:

mammalian germ cell cytogenetic assay

Test material

Test material information

Constituent 1

Reference substance name:

Disodium dihydrogen ethylenediaminetetraacetate

EC Number:

205-358-3

EC Name:

Disodium dihydrogen ethylenediaminetetraacetate

Cas Number:

139-33-3

Molecular formula:

C10H14N2Na2O8

IUPAC Name:

disodium dihydrogen 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetate

Test material form:

solid - liquid: suspension

Details on test material:

- Name of test material (as cited in study report): ethylenedinitrilotetracetic acid disodium salt dihydrate

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Italy

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

water

Details on exposure:

10 ml/kg bw

Duration of treatment / exposure:

6 h and 5 days

Frequency of treatment:

single treatment

Doses / concentrations

Remarks:

Doses / Concentrations:
93 or 186 mg/kg bw
Basis:
other: actually applied

No. of animals per sex per dose:

5 (within 2 independent experiments)

Control animals:

yes, concurrent no treatment

Examinations

Tissues and cell types examined:

secondary spermatocytes, and SCE in bone marrow

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Remarks:

Clinical observations are not reported

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Any other information on results incl. tables

EDTA-Na2H2 did not induce significant increases in aneuploidy in both germ and somatic cells at both exposure levels and meiotic stages tested. Table 1 – Effects of EDTA on the hyperhaploidy index in mouse secondary hepatocytes

 

Treatment	Meiotic stage treated	Metaphases analyzed
		Total	Hyperhaploid (n= 21-22)
			N	% +/- SE
-	-	500	2	0.4 +/- 0.3
EDTA (93 mg/kg bw)	Diakinesis – metaphase I	500	3	0.6 +/- 0.3
EDTA (186 mg/kg bw)	Diakinesis – metaphase I	500	7	1.4 +/- 0.5
EDTA (186 mg/kg bw)	Mid-pachytene	500	3	0.6 +/- 0.3

No statistically significant changes

 

Table 2 – Aneuploidy incidence and SCE/cell level in bone marrow 2^ndgeneration metaphases (M2)

 

EDTA (mg/kg bw)	M2 metaphases analysed			SCE/cell (mean +/- SE)
	Total	Hyperploid (2n = 41-42)
		N	% +/- SE
0	500	3	0.6 +/- 0.4	3.07 +/- 0.18
93	500	8	1.6 +/- 0.6	2.86 +/- 0.17
186	500	5	1.0 +/- 0.5	3.30 +/- 0.15

No statistically significant changes

 

Table 3 – Effects of EDTA on cell replication kinetics in mouse bone marrow cells

 

EDTA (mg/kg bw)	Metaphases analyzed				AGT (h) (mean +/- SE)
	Total	%M1	%M2	%M3
0	500	3.6	95.4	1.0	10.13 +/- 0.06
93	500	9.2	89.6	1.2	10.42 +/- 0.11
186	500	11.0	88.8	0.2	10.58 +/- 0.17

AGT = average generation time, regression analysis showed a significant linear increase with dose of EDTA (p<0.001)

Applicant's summary and conclusion

Conclusions:

EDTA-Na2H2 did not induce significant increases in aneuploidy in both germ and somatic cells at both exposure levels and meiotic stages tested.

Executive summary:

EDTA-Na2H2 was assayed in tests for aneuploidy based on chromosome counting in mouse germ and somatic cells. In the present experiments

In the cytogenetic assays for aneuploidy both in the germ and somatic cells of the mouse, negative results were obtained following the i.p. administration of 93 and 186 mg EDTA per kg b.w.