Reaction mass of methyl acetate and methanol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Methyl acetate

EC Number:

201-185-2

EC Name:

Methyl acetate

Cas Number:

79-20-9

Molecular formula:

C3H6O2

IUPAC Name:

Methyl acetate

Test material form:

liquid

Method

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100. Escherichia coli WP2uvrA

Metabolic activation:

with and without

Metabolic activation system:

S9 from rat liver homogenate

Test concentrations with justification for top dose:

0, 4, 20, 100, 500, 2500 and 5000 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

N-ethyl-N-nitro-N-nitrosoguanidine

benzo(a)pyrene

other: 2-Aminoanthracene

Rationale for test conditions:

range finding test

Evaluation criteria:

statistically significant dose dependent increase

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Test results 5

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not specified

Positive controls validity:

valid

Any other information on results incl. tables

 

TA100
DOSE	Without Activation		With Activation
µg/Plate	Mean Value Exp 1	Mean Value Exp 2	Mean Value Exp 1	Mean Value Exp 2
0	168	129	168	148
4	178	137	178	136
20	170	133	170	137
100	169	140	169	146
500	185	139	185	135
2500	154	138	154	133
10000	157	148	157	139
+ ctrl	425	374	546	374

 

 

TA1535
DOSE	Without Activation		With Activation
µg/Plate	Mean Value Exp 1	Mean Value Exp 2	Mean Value Exp 1	Mean Value Exp 2
0	17	10	15	11
4	16	10	14	14
20	17	9	16	12
100	15	11	12	10
500	12	10	14	11
2500	14	9	15	13
10000	18	7	12	8
+ ctrl	350	297	114	102

 

 

TA1538
DOSE	Without Activation		With Activation
µg/Plate	Mean Value Exp 1	Mean Value Exp 2	Mean Value Exp 1	Mean Value Exp 2
0	16	10	19	13
4	16	10	16	15
20	16	11	19	14
100	19	11	19	16
500	14	11	21	12
2500	17	9	19	13
10000	14	9	19	15
+ ctrl	439	376	491	348

 

 

TA98
DOSE	Without Activation		With Activation
µg/Plate	Mean Value Exp 1	Mean Value Exp 2	Mean Value Exp 1	Mean Value Exp 2
0	24	22	30	28
4	22	24	32	28
20	23	21	19	30
100	25	24	32	29
500	23	24	32	31
2500	22	24	30	28
10000	24	24	31	28
+ ctrl	342	402	471	487

 

 

TA1537
DOSE		Without Activation			With Activation
µg/Plate		Mean Value Exp 1		Mean Value Exp 2		Mean Value Exp 1		Mean Value Exp 2
0		11		9		11		12
4		9		8		10		10
20		11		8		10		9
100		11		9		10		10
500		9		8		9		9
2500		11		11		11		9
10000		14		7		10		8
+ ctrl		98		126		98		106

 

 

WP2uvrA
DOSE	Without Activation		With Activation
µg/Plate	Mean Value Exp 1	Mean Value Exp 2	Mean Value Exp 1	Mean Value Exp 2
0	72	55	74	57
4	75	54	75	53
20	74	55	77	56
100	69	61	78	55
500	75	55	75	52
2500	75	57	79	52
10000	76	55	75	55
+ ctrl	280	509	216	446

 

Applicant's summary and conclusion

Conclusions:

Not mutagenic with or without metabolic activation

Executive summary:

Methyl acetate was tested for mutagenicity with the strains TA 100, TA 1535, TA 1537, TA 1538, TA 98 of Salmonella typhimurium and Escherichia coli WP2uvrA. The mutagenicity studies were conducted in the absence adn in the presence of a metabolizing system derived from rat liver homogenate. A dose range of 6 different doses from 4 micrograms/plate to 5000 micrograms/plate was used. Control plates without mutagen showed that the number of spontaneous revertant colonies was similar to that described in the literature. All the positive control compounds gave the expected increase in the number of revertant colonies.

Toxicity: The test compound proved to be not toxic to the bacterial strains at 5000 micrograms/plate. 5000 micrograms/plate was chosen as the top dose level for the mutagenicity study.

Mutagenicity: In the absence of the metabolic activation system the test compound did not show a dose dependent increase in the number of revertants in any of the bacterial strains. Also in the presence of a metabolic activation system, treatment of the cells with Methyl acetate did not result in relevant increases in the number of revertant colonies.

 

Summarizing, it can be stated that Methyl acetate is not mutagenic in these bacterial test systems either with or without exogenous metabolic activation at the dose levels investigated.