Sodium [N-[2-[bis(carboxymethyl)amino]ethyl]-N-(2-hydroxyethyl)glycinato(4-)]ferrate(1-)

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions For read-across justification refer to section 13.

Data source

Reference

Reference Type:

publication

Title:

Further evidence for the aneuploidogenic properties of chelating agents: induction of micronuclei in mouse male germ cells by EDTA

Author:

Russo A, Levis AGl

Year:

1992

Bibliographic source:

Environ Mol Mutagen 19, 125-131

Materials and methods

Principles of method if other than guideline:

In vivo mouse micronucleus assay

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

6381-92-6

EC Number:

613-386-6

Cas Number:

6381-92-6

IUPAC Name:

6381-92-6

Test material form:

solid - liquid: suspension

Details on test material:

Disodium EDTA 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
- Age at study initiation: 8 -12 weeks

Administration / exposure

Route of administration:

intraperitoneal

Details on exposure:

- Application volume: 10 ml/kg bw

Duration of treatment / exposure:

24 or 48 h (2 treatment sacrifice intervals)

Frequency of treatment:

single treatment

Doses / concentrations

Remarks:

Doses / Concentrations:
186 mg/kg bw
Basis:

No. of animals per sex per dose:

6 control animals
3 for the 24 h interval
at least 4 for the 48 h interval

Control animals:

yes

Positive control(s):

1 mg/kg bw Mitomycin C

Examinations

Tissues and cell types examined:

bone marrow; polychromatic erythrocytes

Details of tissue and slide preparation:

Bone marrow smears were prepared following a standard protocol [MacGregor et al., 1987]

Evaluation criteria:

The frequency of MN induced in bone marrow was estimated by scoring 2,000 polychromatic erythrocytes (PCE) per animal at both time intervals. The frequency of normochromatic erythrocytes (NCE) was also assessed, to verify the possible cytotoxicity of each tested dose through the PCE/NCE ratio.

Statistics:

The frequencies of MN observed in each experimental group were pooled and the significance of differences between treated and control groups were evaluated by using the G test. The mean frequency of aberrations per cell and the PCE/NCE ratio were compared by the Student t-test after square root transformation of values.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not valid

Positive controls validity:

valid

Any other information on results incl. tables

Table 1: Frequency of MN in Bone Marrow PCEs After Treatment With EDTA at Two Time Intervals

	PCE		NCE		PCE/NCE ratio
	Total	+MN ( ‰ ± SE)	Total	+MN ( ‰ ± SE)	PCE/NCE
Controls	11,810	21 (1 .8 ± 0.4)	12,014	14 (1.2 ± 0.3)	1.09 ± 0.09
MMC 24 hr	6,149	93 (15.1 ± 1.6)***	6,085	22 (3.6 ± 0.8)	1.01 ± 0.05
MMC 48 hr	8,302	89 (10.7 ± 1.1)***	9,881	70 ( .1 ± 0.8)	0.87 ± 0.08
EDTA 24 hr	12,153	18 (1 .5 ± 0.3)	13,820	15 (1 .1 ± 0 .3)	0 .94 ± 0.1 1
EDTA 48 hr	8,019	20 (2 .5 ± 0.6)	7,514	15 (2 .0 ± 0.5)	1 .05 ± 0 .09

PCE: polychromatic erythrocytes

NCE: normochromatic erythrocytes

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
EDTA-Na2H2 did not induce micronuclei in the bone marrow of male mice following ip injection.

Executive summary:

In the present study the effects of EDTA-Na2H2 dihydrate and two clastogens, adriamycin (ADM) and mitomycin C (MMC), and of the aneuploidogenic agent chloral hydrate (CH) were evaluated for the induction of micronuclei in bone marrow. All compounds were tested at a single dose level and at two time intervals, 24 and 48 h. EDTA-Na2H2 did not induce micronuclei in the bone marrow of male mice following ip injection.