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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes
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): TAME
- Physical state: clear aqueous liquid
- Analytical purity: 98.4%
- Purity test date: 23 April 1990
- Lot/batch No.: 25.-30.11.89 sample nr: 500763
- Expiration date of the lot/batch: 24 nov 1992
- Storage condition of test material: refrigirator

Method

Target gene:
his
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9 (from liver homogenate from aroclor 1254 pretreated SD rats)
Test concentrations with justification for top dose:
0, 8, 40, 200, 1000, 2000 and 5000 ug/plate
Vehicle / solvent:
methanol (not tested as negative control only, from literature it is known that methanol is negative)
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine, 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: none
- Exposure duration: 2 days at 37 degree centigrade

A toxicity pre-test, an initial and a repeat test were performed.
Evaluation criteria:
A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA 1535, 100 and 98, this increase should be about twice the amount of the negative controls, whereas for TA 1537, at least a threefold increase should be reached.
Statistics:
After completion of scoring, mean of revertant colonies and standard deviation for each dose are determined.

Results and discussion

Test results
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:
other: weak strain-specific bacteriotoxic effect from 200 µg/plate
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Doses up to and including 40 μg did not cause toxicity. At higher doses, TAME had a weak strain-specific bacteriotoxic effect. Nevertheless all the doses could be used for assessment. No indications of mutagenic effects were seen at doses up to 5,000 g/plate, with or without metabolic activation with male Sprague-Dawley liver S9 fraction.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion