2-dimethylaminoethyl methacrylate

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:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Reference 2

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

Test material information

Constituent 1

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 2^ndadministration
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 2^ndadministration
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.