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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comprehensive test programme using test procedures in accordance with accepted standard methods, sufficiently documented.

Data source

Reference
Reference Type:
publication
Title:
The results of microbial mutation test for forty-three industrial chemicals.
Author:
Shimizu, H. et al.
Year:
1985
Bibliographic source:
Jpn J Ind Health 27: 400-419

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Methanol
- Analytical purity: 99.6 % pure, no further data
- Other: Source: Wako Pure Chemical Industries, LTD., Osaka, Japan

Method

Target gene:
His-operon, Trp-operon (E. coli)
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
E. coli WP2 uvr A
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Liver S9 fraction of KC500-pretreated rats
Test concentrations with justification for top dose:
5, 10, 50, 100, 500, 1000, 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
no
Positive controls:
yes
Remarks:
0.01 and 5.0 µg/plate, respectively
Positive control substance:
other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) without S9, benzo(a)pyrene (B(a)P) with S9
Remarks:
TA100
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
no
Positive controls:
yes
Remarks:
both 5.0 µg/plate, respectively
Positive control substance:
other: N-ethyl -N'-nitro-N-nitrosoguanidine (ENNG) without S9, 2-aminoanthracene (2AA) with S9
Remarks:
TA1535both 5.0 µg/plate, respectively
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
no
Positive controls:
yes
Remarks:
0.05 and 5.0 µg/plate, respectively
Positive control substance:
other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) without S9, 2-aminoanthracene (2AA) with S9
Remarks:
WP2 uvrA
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
no
Positive controls:
yes
Remarks:
0.05 and 5.0 µg/plate, respectively
Positive control substance:
other: 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) without S9, benzo(a)pyrene (B(a)P) with S9
Remarks:
TA98
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
no
Positive controls:
yes
Remarks:
80.0 and 5.0 µg/plate, respectively
Positive control substance:
other: 9-aminoacridine (9AC) without S9, benzo(a)pyrene (B(a)P) with S9
Remarks:
TA1537
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
no
Positive controls:
yes
Remarks:
0.25 and 5.0 µg/plate, respectively
Positive control substance:
other: 4-nitroquinoline-1-oxide (4NQO) without S9, benzo(a)pyrene (B(a)P) with S9
Remarks:
TA1538
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: duplicates

DETERMINATION OF CYTOTOXICITY
- Method: other: growth inhibition of revertant clones
Evaluation criteria:
Doubling of revertant numbers in comparison to control and dose-response correlation.

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified

Any other information on results incl. tables

Maximum number of revertants:

 

Control (water) [mean±SD]

Test substance (µg/plate)

Strain

-S9

+S9

-S9

+S9

TA100

149±17.1

161±16.2

175 (100)

180 (50)

TA1535

28±6.9

15±3.6

35 (50)

17 (5000)

TA98

29±6.2

39±8.6

42 (50)

39 (1000)

TA1537

16±6.4

21±8.1

22 (5000)

35 (5)

TA1538

21±5.5

28±7.0

18 (500)

31 (5)

E.coli WP2 uvrA

32±7.3

33±10.3

36 (5000)

43 (10)

The test substance was not mutagenic in the tested strains up to 5000 µg/plate.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative