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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:
experimental study
Adequacy of study:
key study
Study period:
from 22 February 1994 to 25 March 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A well documented not GLP study according to OECD guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
The assay is based on the use of 5 Salmonella typhimurium tester strains that revert from histidine dependence (auxotrophy) to histidine independence (prototrophy) in the presence of a genotoxic agent, with or without a metabolic activation system.
This study was carried out with the pre-incubation method.
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Thiophene-2-ethylamine
EC Number:
250-196-9
EC Name:
Thiophene-2-ethylamine
Cas Number:
30433-91-1
Molecular formula:
C6H9NS
IUPAC Name:
2-(2-thienyl)ethanamine
Constituent 2
Reference substance name:
2-Thiopheneethanamine
IUPAC Name:
2-Thiopheneethanamine
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): SR 26825
- Lot/batch No.: 4SNL001

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Metabolic activation system:
S-9 mix (2.5%) from Aroclor 1254-induced rat liver
Test concentrations with justification for top dose:
Toxicity study (TA98): pre-incubation method and plate incorporation method: 0 - 100 - 250 - 500 - 1000 - 2500 and 5000 µg/plate
Genotoxicity study: 0 - 250 - 500 - 1000 - 2500 and 5000 µg/plate on the 5 strains
Vehicle / solvent:
Dimethyl sulfoxide (100 µl/plate)
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
mitomycin C
other: 2-aminoanthracene and Danthron
Details on test system and experimental conditions:
The preliminary toxicity study on TA98 was performed at concentrations of 100, 250, 500, 1000, 2500 and 5000 µg/plate using the plate incorporation method and the pre-incubation method. In view of the results obtained in the toxicity test, the pre-incubation method was retained for the main genetoxicty study and the concentrations tested were: 250, 500, 1000, 2500 and 5000 µg/plate for the five tester strains. Assays were performed in triplicate for each concentration of SR 26825.
Evaluation criteria:
Criteria for bacterial toxicity are:
1- reduced number of revertant colonies/plate,
2- sparsity of the bacterial background lawn when compared with control plates.
For the genotoxicity test, results are expressed as the number of His+ revertant colonies/plate.
For each concentration, the net number of His + revertant colonies/ plate can be calculated by substracting the mean number obtained for the 3 control plates from the mean number obtained for the 3 test compound plates.
The compound is considered genotoxic:
• if the increase in the number of revertants is concentration-related,
• if, at one concentration tested (at least), the number of revertant colonies is equal to or greater than twice the number of spontaneous revertants observed with TA98, TA100 and TA102 and three times that observed with TA1535 and TA1537,
• if the positive response is reproducible in an independent assay.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: positive at 5000 µg/plate on all tester strains with and without metabolic activation but negative at lower concentrations (except for TA102 where a slight toxic effect was noted from 1000 µg/plate with and without metabolic activation).
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
A very marked toxic effect was noted at 5000 µg/plate on the five tester strains with and without S-9 mix. In addition, at 2500 µg/plate, toxicity of the compound was mainly observed without S-9 rnix on TA98, TA102, TA1535 and TA1537. No effect was noted on TA100. At this same concentration, no effect was noted with S-9 mix except on TA102 and TA1537.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Under these conditions, with or without a metabolic activation system, SR 26825 did not induce any increase in the number of His+ revertant colonies/plate, whatever the concentration tested.
Besides, the positive controls, with S-9 mix when required, induced a marked increase in the number of revertant colonies for all tester strains, therefore confirming the sensitivity of the strains and the activity of S-9 mix.
In conclusion, SR26825 was not genotoxic in the Ames test with or without metabolic activation.

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