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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1987
Reference Type:
publication
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Only 4 strains of Salmonella typhimurium were tested
Principles of method if other than guideline:
Only 4 strains of Salmonella typhimurium were tested
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl methacrylate
EC Number:
201-297-1
EC Name:
Methyl methacrylate
Cas Number:
80-62-6
Molecular formula:
C5H8O2
IUPAC Name:
methyl methacrylate
Test material form:
liquid
Specific details on test material used for the study:
Supplied by Rohm and Haas; 99+% pure

Method

Target gene:
his+
Species / strain
Species / strain / cell type:
other: S. typhimurium TA 1535, TA97, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
AROCLOR 1254 induced rat and Syrian hamster liver S9 mix.
Test concentrations with justification for top dose:
33 - 6666 ug/plate
Test concentrations: 0, 33, 100, 1000, 3333, 6666 µg/plate
At 6666 µg/plate slight cytotoxicity was observed
Vehicle / solvent:
Not specified: vehicles used included water, DMSO, ethanol or acetone
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: without S9: 4-nitro-o-phenylenediamine (TA98). With S9: 2-aminoanthracene (all strains)
Details on test system and experimental conditions:
NUMBER OF REPLICATIONS:
- Number of cultures per concentration: triplicate
- Number of independent experiments: two

METHOD OF TREATMENT/ EXPOSURE:
- Solvent: DMSO
- Cell density at seeding (if applicable):
- After addition of soft agar, the contents of each tube was poured onto minimal medium

TREATMENT AND HARVEST SCHEDULE:
- Preincubation period, if applicable: 20 minutes, 37 °C
- Exposure duration/duration of treatment: 48 hours, 37 °C
Evaluation criteria:
An individual trial was judged (+) mutagenic if a dose related increase over the corresponding solvent control was seen, and it was judged weakly mutagenic (+W) if a low dose response was seen. A trial was considered questionable (?) if a dose related increase was judged insufficiently high to justify a call of "+W" if only a single dose was elevated over control or if a non-dose related increase was seen. A chemical was judged weakly mutagenic "+W' or mutagenic "+" if it produced a reproducible, dose related increase in his+ revertants over the corresponding solvent controls in replicate trials.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Mutagenicity of Methyl methacrylate in Salmonella Typhimurium

 

 

Revertants per plate (a,b)

Strain

Dose

(µg/plate)

-S9

+S9 (rat)

+S9 (hamster)

TA100

0

140 +/- 6.7

141 +/- 8.0

131 +/- 4.7

 

33

118 +/- 5.6

-

-

 

100

122 +/- 21.1

157 +/- 10.2

143 +/- 9.9

 

333

126 +/- 10.5

143 +/- 7.1

145 +/- 4.1

 

1000

136 +/- 5.0

138 +/- 11.6

130 +/- 8.5

 

3333

129 +/- 8.8

121 +/- 10.7

116 +/- 6.2

 

6666

-

(c) 48+/- 16.3

(c) 65+/- 3.5

 

 

 

 

 

TA1535

0

26 +/- 4.4

9 +/- 1.5

6 +/- 0.6

 

33

22 +/- 2.2

-

-

 

100

18 +/- 1.7

6 +/- 1.2

143 +/- 9.9

 

333

17+/- 2.5

8 +/- 2.1

145 +/- 4.1

 

1000

16 +/- 2.3

7 +/- 1.0

130 +/- 8.5

 

3333

16 +/- 2.9

7 +/- 1.2

116 +/- 6.2

 

6666

-

(c) 4+/- 0.9

(c) 65+/- 3.5

 

 

 

 

 

TA97

0

145 +/- 4.5

180 +/- 9.4

248 +/- 105.5

 

33

145 +/- 13.6

-

-

 

100

151 +/- 16.6

175 +/- 11.6

152 +/- 9.1

 

333

138 +/- 14.0

190 +/- 2.3

157 +/- 10.6

 

1000

149 +/- 1.0

195 +/- 4.3

158 +/- 6.3

 

3333

156 +/- 3.8

166 +/- 7.3

169 +/- 4.8

 

6666

-

(c) 64 +/- 31.8

(c) 89+/- 7.7

 

 

 

 

 

TA98

0

22 +/- 2.3

2.9 +/- 4.9

26 +/- 2.0

 

33

20 +/- 2.4

-

-

 

100

18 +/- 1.5

32 +/- 2.2

24 +/- 2.6

 

333

23 +/- 3.0

26 +/- 3.2

25 +/- 1.0

 

1000

17 +/- 1.0

27 +/- 1.5

22 +/- 2.1

 

3333

19 +/- 0.3

16 +/- 2.3

18 +/- 1.2

 

6666

-

(c) 0 +/- 0.0

(c) 5 +/- 2.1

a)     S9 fractions prepared from the liver of Acrolor 1254-induced male Sprague-Dawley rats and male Syrian hamsters

b)    Mean +/- standard error

c)     Slightly toxic

Applicant's summary and conclusion

Conclusions:
Methyl methacrylate was tested in bacterial reverse mutation test in Salmonella typhimurium (Ames test) in 4 strains (TA97, TA98, TA100 and TA1535) at test concentrations of 33 - 6666 µg/plate. Slight cytotoxicity was observed at 6666 µg/plate.
Methyl methacrylate was not mutagenic in bacterial reverse mutation test in Salmonella typhimurium (TA97, TA98, TA100 and TA1535).
Executive summary:

Methyl methacrylate was tested in  bacterial reverse mutation test in Salmonella typhimurium (Ames test) in 4 strains (TA97, TA98, TA100 and TA1535) at test concentrations of 33 - 6666 µg/plate. Slight cytotoxicity was observed at 6666 µg/plate. Methyl methacrylate was not mutagenic in  bacterial reverse mutation test in Salmonella typhimurium strains TA97, TA98, TA100 and TA1535.