Registration Dossier

Diss Factsheets

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993
Reference Type:
secondary source
Title:
Atochem (1993), Micronucleus test in Mice, CIT 9776 MAS
Author:
Atochem
Year:
2003
Bibliographic source:
cited in: OECD SIDS, 2-Dimethylaminoethylmethacrylate, CAS No: 2867-47-2, 07/2003

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
2-dimethylaminoethyl methacrylate
EC Number:
220-688-8
EC Name:
2-dimethylaminoethyl methacrylate
Cas Number:
2867-47-2
Molecular formula:
C8H15NO2
IUPAC Name:
2-(dimethylamino)ethyl methacrylate
Test material form:
liquid
Specific details on test material used for the study:
TEST MATERIAL:
- Name of test material (as cited in study report): Dimethylaminoethyl methacrylate (MADAME)

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
-Strain: OF1/ICO: OF1 (IOPS Caw)
- Source: Iffa Crédo (69210 L'Arbresle, France)
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: males 21-36 g, females 24-29 g
- Housing: in polycarbonate cages (33.5 X 18.7 X 13.0 cm) and each cage contained 5 mice of the same sex and group
- Diet: A04 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France) ad libitum
- Water: filtered tap water ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2
- Humidity (%): 50±20
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Physiological solution of 0.9% NaCl
Details on exposure:
- Application volume: 10 ml/kg bw
Duration of treatment / exposure:
Sampling time 14 or 48 hours after second administration.
Frequency of treatment:
2 administrations separated by 24 hrs
Doses / concentrations
Remarks:
Doses / Concentrations:
200 mg/kg bw
Basis:

No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
25 mg/kg bw cyclophosphamide (2 i.p. injections)

Examinations

Tissues and cell types examined:
Bone marrow smeares were prepared 24 and 48 hrs after the 2nd administration. The presence of micronuclei was analysed in 2000 polychromatic erythrocytes (PE) per mouse, and the PE/NE ratio was determined.
Details of tissue and slide preparation:
At the time of sacrifice, all the animals were sacrificed after CO2 inhalation in excess. The femurs of the mice were removed and the bone marrow eluted out using fetal calf serum. After centrifugation, the supernatant was removed and the cells in the sediment were suspended by shaking. A drop of this cell suspension was placed and spread on a slide. The slides were air-dried and stained with May-Grünwald-Giemsa. Two slides/animal were prepared, but only one was used for scoring. All the slides were coded for scoring.
Evaluation criteria:
The following criteria were used as an aid for deterrnining a positive response:
- a statisticaliy significant increase in the number of MPE for at least one of the sampling times when cornpared to the vehicle group,
- this increase should double the number of MPE of our historical data.
The results were considered negative if the above criteria were not fully met.
Statistics:
At each sarnpling time, the mean number of micronucleated polychromatic erythrocytes (MPE) and the PE/NE ratio from the treated groups were compared to the simultaneous vehicle groups. The intergroup comparison was performed using for MPE, the X² test, and for the PE/NE ratio, the Student's "t" test, in which p = 0.05 was used as the lowest level of significance.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
cytotoxicity
Additional information on results:
In all groups treated with the TS, the mean values of micronucleated polychromatic erythrocytes were similar to those of their respective vehicle control groups at each sampling time, and no statiscally significant differences were observed. The PE/NE ratio did not differ from that of the respective vehicle control group.

Any other information on results incl. tables

Summary of the test results:

 

Group

Dose

(mg/kg bw)

MPE/PE

PE/NE ratio

Mean

SD

Mean

SD

Time of sacrifice: 24 hours after the 2ndadministration

Vehicle

-

2.0

0.8

0.7

0.2

Test substance

200

1.9

1.1

0.6

0.2

CPA

25

18.2***

3.8

0.4***

0.1

 

Time of sacrifice: 48 hours after the 2ndadministration

Vehicle

-

1.9

0.8

0.9

0.4

Test substance

200

1.7

1.0

1.2

0.6

 *** = P<0.001

Vehicle: physiological solution (0.9% NaCl)

CPA: cyclophosphamide

PE: polychromatic erythrocytes

NE: normochromatic erythrocytes

MPE/PE: micronucleated polychromatic erythrocytes/2000 polychromatic erythrocytes

SD: standard deviation

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The TS did not induce cytogenetic damage to the bone marrow cells of mice when treated twice separated by 24 hrs by intraperioneal route at 200
mg/kg in the micronucleus test.
Executive summary:

The study was performed according to OECD TD 473 in compliance with GLP.

Swiss OF1/ICO:OF1 IFFA-CREDO mice (5 males and 5 females per group) received two administrations separated by 24 hrs of 200 mg/kg bw TS by the intraperitoneal route. The application of the vehicle (0.9% NaCl solution) served as negative control, cyclophosphamide at 25 mg/kg bw (two-times i.p. injection) served as the positive control. The test animals were killed 24 or 48 hrs after the 2nd administration and bone marrow smears were examined for the presence of micronuclei in 2000 polychromatic erythrocytes (PE) per mouse and for the PE/NE ratio. The number of micronucleated polychromatic cells (MPE) in the dosed animals was not significantly different from that of the animals in the control groups. The PE/NE ratio did not differ from that of the respective vehicle control group.

Conclusion: The TS did not induce cytogenetic damage to the bone marrow cells of mice when treated twice separated by 24 hrs by intraperioneal route at 200 mg/kg in the micronucleus test.