2-dimethylaminoethyl methacrylate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Original report is only available in Japanese. Translated report present.

Data source

Reference

Reference 1

Reference Type:

other: summary report

Title:

Unnamed

Year:

1998

Reference 2

Reference Type:

publication

Title:

MHW, Japan (1998) Ministry of Health and Welfare, Toxicity Testing Reports of Environmental ChgmicaIs 6, 539-568

Author:

Ministry of Health and Welfare, Japan

Year:

2003

Bibliographic source:

cited in: OECD SIDS, 2-Dimethylaminoethylmethacrylate, CAS No: 2867-47-2, 07/2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation 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: 2-dimethylaminoethyl methacrylate
- Purity: 99.9%
- Impurities: Hydroquinone monomethyl ether (as polymerization inhibitor) 2000 ppm, dimethyl amino ethanol less than 0.1%, methylmethacrylate less than 0.02%
- Supplier: Sanyo Kasei Co.

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9: Rat liver, induced with phenobarbital and 5,6-benzoflavone

Test concentrations with justification for top dose:

Without S9 mix: 156, 313, 625, 1250, 2500, 5000 µg/plate
With S9 mix: 156, 313, 625, 1250, 2500, 5000 µg/plate
Confirmative test without S9 mix: 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000 µg/plate

Vehicle / solvent:

Distilled water

Controls

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Remarks:

Without S9 mix: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98, WP2 uvrA), Sodium azide (TA1535) and 9-Aminoacridine (TA1537). With S9 mix: 2-Aminoanthracene (all strains).

Details on test system and experimental conditions:

By the preliminary test to decide the highest concentration, toxicity was observed at 5000 ug/plate in the direct method without S9 mix for TA 98 and TA 1537. Then the highest concentration was set at 5000 µg/plate for all tests.

- Procedure: Pre-incubation method
- No. of replicates: 2
- No. of plates/test: 3

Two trial tests were done for all cells and a confirmation test was conducted for TA 98 and TA 1537 which showed positive results in the trial tests.

Evaluation criteria:

1) The revertant colony increase should be more than two times of the control.
2) The revertant colony increase should increase proportionally to the concentration of the test substance (concentration dependency).
3) The same revertant colony increase should be observed repeatedly by more than two tests.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

without

Genotoxicity:

positive

Remarks:

at 2500 and 3000 µg/plate

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

> 3500 µg/plate

Additional information on results:

In the two tests, the test substance caused a revertant colony increase of 2-times as much as that of the control to S. typhimurium TA 1537 at 2500 µg/plate without S9. However, a concentration dependency was not clear. Additionally, a revertant colony increasing tendency was observed for S. typhimurium TA98 at 2500 µg/plate and 5000 µg/plate without S9.
Consequently, to confirm the concentration dependent increase of revertant colonies at 2500 - 5000 µg/plate, the confirmation test was conducted for S. typhimurium strains TA 1537 and TA 98 by the direct method without S9. In this test, toxic effects were observed at 3500 µg/plate and more to TA 98 and TA 1537 without S9 mix. For TA 1537 a revertant colony increase was observed by more than 2-times of the control at 2500 and 3000 µg/plate. Furthermore, a concentration dependency was observed. For TA 98, although a revertant colony increase was observed at 2500 and 3000 µg/plate, it was less than 2-times as much as that of the control.
According to this study, the test substance is considered to be positive in this bacterial reverse mutation test. The number of the induced revertant colonies per mg was calculated to be 3.6/mg.

Any other information on results incl. tables

Number of revertant colonies (mean ± SD):

 

Dose/plate (µg)	Without S9 mix		With S9 mix
	Mean	SD	Mean	SD
1^stExperiment
Salmonella typhimurium TA 98
0 (Water)	20	4	35	9
625			36	3
1250	20	4	42	7
2500	35	8	37	5
5000	34*	14	48	9
AF-2 0.1 µg	389	11
2-AA			275	23
Salmonella typhimurium TA 1537
0 (Water)	7	1	12	4
625			14	1
1250	7	1	15	2
2500	15	4	18	3
5000	4*	2	17	3
9-AA 80 µg	946	132
2-AA			89	12
2^ndExperiment
Salmonella typhimurium TA 98
0 (Water)	26	6	37	7
625			35	5
1250	23	7	34	10
2500	39	2	40	6
5000	38*	14	43	14
AF-2 0.1 µg	406	31
2-AA			372	20
Salmonella typhimurium TA 1537
0 (Water)	6	1	19	2
625			19	5
1250	8	3	16	2
2500	15	3	17	2
5000	2*	2	27	3
9-AA 80 µg	964	18
2-AA			90	9
Confirmation Test
Salmonella typhimurium TA 98
0 (Water)	25	2
1000	23	2
1500	26	6
2000	33	3
2500	44	7
3000	42	6
3500	34*	10
4000	18*	3
4500	11*	4
5000	14*	4
AF-2 0.1 µg	365	26
Salmonella typhimurium TA 1537
0 (Water)	5	1
1000	7	2
1500	9	2
2000	8	1
2500	13	3
3000	15	5
3500	7*	2
4000	4*	1
4500	3*	1
5000	5*	3
9-AA 80 µg	933	29

 

* = Toxic effect was observed.

Applicant's summary and conclusion

Conclusions:

Interpretation of results:
positive without metabolic activation

The test substance was mutagenic in Salmonella typhimurium TA1537 without an exogenous metabolic activation system.

Executive summary:

The study was performed according to OECD TG 471 & TG 472 under GLP conditions.

The test substance induced mutations only in S. typhimurium TA1537 without metabolic activation at 2500 and 3000 µg/plate. The number of the induced revertant colonies/mg was calculated as 3.6/mg. Toxicity was observed at 5000 µg/plate (TA98, TA1537) without S9 mix. In a confirmation test, toxicity was observed at more than 3500 µg/plate (TA98, TA1537) without S9 mix.

Conclusion: The test substance was mutagenic in Salmonella typhimurium TA1537 without an exogenous metabolic activation system.