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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
Study period:
1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
May 26, 1983
Deviations:
not specified
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
impurity
Type:
impurity
Type:
impurity
Test material form:
liquid
Specific details on test material used for the study:
TEST MATERIAL NAME (as stated in study report): TK 12437 (Irgastab CH 302)

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor; Batch No. 08520495
- Expiration date of the lot/batch: July, 1996
- Purity: within the product specifications

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
S9 fraction from livers of Aroclor 1254 treated rats
Test concentrations with justification for top dose:
Preliminary Toxicity / Range-Finding Test (TA 100 and WP2): 20 to 5000 µg/plate.
Mutagenicity Test: Original experiment - 625 - 5000 µg/plate; Confirmatory experiment - 78 - 625 µg/plate. Doses in original experiment were chosen based on results of range-finding test. Because toxic effects occurred on the growth of revertant colonies in the original experiment with strain TA 100 (without and with activation) and with strain TA 1537 (with activation) the experiments with these strains were repeated with four concentrations in the ränge of 78.1 - 62 5 µg/plate
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
9-aminoacridine
2-nitrofluorene
sodium azide
cyclophosphamide
other: 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: about 48 hours at 37 ± 1.5°C in darkness

NUMBER OF REPLICATIONS: two plates per test concentration
Rationale for test conditions:
per standard references, including OECD 471 test guideline
Evaluation criteria:
Assay acceptance criteria:
A test is considered acceptable if the mean colony counts of the control values of all strains are within the acceptable ranges and if the results of the positive controls meet the criteria for a positive response.

Criteria for a positive response:
The test substance is considered to be mutagenic in this test system if:
- A positive effect is observed in one strain and the effect can be reproduced in a confirmatory experiment.
- A positive effect is observed in two or more strains.

A positive effect is defined as an increase of the mean number of revertants per plate for any concentration above that of the negative control by at least a factor of 2,0 with strains TA 98, TA 1535, TA 1537 and WP2 uvrA, or by a factor of at least 1.5 with strain TA 100. Generally a concentration-related effect should be demonstrable.

Results and discussion

Test results
Species / strain:
bacteria, other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
In a standard Ames Test, Irgastab CH 302 did not induce gene mutations in bacteria with our without metabolic activation.