2-tert-butylaminoethyl 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:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Review by Japanese government and included in the SIDS dossier for 2-dimethylaminoethyl methacrylate as Klimisch 1.

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

2-Dimethylaminoethyl methacrylate SIDS Initial Assessment Report for SIAM 14

Author:

OECD SIDS

Year:

2002

Bibliographic source:

OECD SIDS Initial Assessment Report For SIAM 14, Paris, France, 26-28 March 2002

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

1989

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:

MADAME

IUPAC Name:

MADAME

Constituent 2

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:

other: liquid

Details on test material:

Purity <99.0%

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

Summary does not include these details

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

Negative control, distilled water
Positive control: Cyclophosphamide , physiological saline (0.9% NaCl)

Details on exposure:

Single oral (gavage) dose followed by sampling at 24hour, 48hour and 72 hours after dosing.

Duration of treatment / exposure:

Single oral (gavage) dose followed by sampling at 24hour, 48hour and 72 hours after dosing.

Frequency of treatment:

Single dose

Post exposure period:

Up to 72 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
1000 mg/kg limit dose
Basis:
nominal in water

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide, dose 40mg/kg bodyweight

Examinations

Tissues and cell types examined:

Polychromatic erythrocytes from the bone marrow in the femur.

Details of tissue and slide preparation:

Summary does not include these details

Evaluation criteria:

Cytotoxicty was assess by comparing the ratio of the PCE (polychromatic erythrocytes) the NCE (normochromatic erthrocytes follwing and staining. A decrease in the PCE/NCE ratio compared to the negative controls would be taken to indicate cytotoxicty and confirm that the test substnace or a metaboite have reached the bone marrow.

Statistics:

Summary does not include these details

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid

Any other information on results incl. tables

Sampling time: 24 hours

Group	Dose mg/kg Bwt	PCE with Micronuclei	Micronuclei in 1000 PCE	PCE/NCE (mean)
Solvent control	0	0.06	0 - 2	1000/554
2 -dimethylaminoethyl methacrylate	1000	0.03	0 - 2	1000/653
Cyclophosphamide	40	0.75	1 - 13	1000/742

Sampling Time: 48 hours

Group	Dose mg/kg bw	PCE with Micronuclei	Micronuclei in 1000 PCE	PCE/NCE (mean)
Solvent control	0	0.04	0 - 2	1000/680
2 -dimethylaminoethyl methacrylate	1000	0.04	0 - 1	1000/744

Sampling time: 72 hours

Group	Dose mg/kg bw	PCE with Micronuclei	Micronuclei in 1000 PCE	PCE/NCE (mean)
Solvent control	0	0.06	0 - 4	1000/594
2 -dimethylaminoethyl methacrylate	1000	0.09	0 - 2	1000/506

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
2-dimethylaminoethyl methacrylate was not clastogenic in vivo in the mouse micronucleus test at a 1000 mg/kg limit dose which produced toxic effect in the mice in a preliminary study. There was no indication of cytotoxicity in the bone marrow.

Executive summary:

Type : Micronucleus assay

Species : mouse

Sex : male/female

Strain : NMRI

Route of admin. : gavage

Exposure period : one dose

Doses : 1000 mg/kg (maximum tolerated dose)

Result : negative

Method : OECD Guideline 474 "Genetic Toxicology: Micronucleus Test"

Year : 1989

GLP : yes

Test substance : as prescribed by 1.1 - 1.4

Remark : In comparison with the corresponding negative controls there was no

substantial enhancement in the frequency of the detected micronuclei at

any preparation interval after application of the test article. The mean values

of micronuclei observed after treatment with MADAME were in the same

range compared to the negative control groups. In the positive control group

a distinct increase of induced micronuclei frequency was observed.In

conclusion, the test article did not induce micronuclei as determined by the

micronucleus test in the bone marrow cells of the mouse.

Source : Roehm,

EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)

Test condition : Group: 5 males and 5 females

Negative control: distilled water

Positive control: Cyclophosphamid in physiological serum (NaCl)

Dose: 40 mg/kg

Bone marrow preparation: 24, 48 and 72 hrs after application.

Analysis : 1000 PCE (Polychromatic Erythrocytes) per animal

By a preliminary test, 1000 mg/kg b.w. was estimated to be the maximum

tolerated dose. The animals expressed toxic reactions. After treatment with

the test article the ratio between PCEs and NCEs was not affected as

compared to the corresponding negative controls, thus indicating no

cytoyoxic effects.

Conclusion

2-dimethylaminoethyl methacrylate was not clastogenic in vivo in the mouse micronucleus test at a 1000 mg/kg limit dose.