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Toxicological information

Genetic toxicity: in vivo

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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

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.

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