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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
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: “Commission Directive 2000132/EC, L1362000, Annexe 4D, dated May 19,2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Batch: C02421-1620
Purity: 98.6%

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 liver fractions of rats, induced with phenobarbital/ ß-naphthoflavone.
Test concentrations with justification for top dose:
Concentration range in the main test (with metabolic activation): 33 ... 5000 µg/plate
Concentration range in the main test (without metabolic activation): 33 ... 5000 µg/plate
Vehicle / solvent:
Solvent: Deionised water

Results and discussion

Test results
Species / strain:
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:
no cytotoxicity
Remarks:
(> 5000 µg/plate)
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
No toxic effects, evident as a reduction in the number of revertants, occurred in the test groups with and without metabolic activation.

The plates incubated with the test item showed normal background growth up to 5000 pglplate with and without S9 mix in all strains used.

No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with ucb 6474 at any concentration level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.

The number of colonies did not quite reach the lower limit of our historical control data in strain TA 1535 (solvent control, exp. 1,without S9 mix) and in strain WP2 uvrA (negative control, exp. 11,with S9 mix). Since these deviations are rather small, these effects are considered to be based upon biologically irrelevant fluctuations in the number of colonies and have no detrimental impact on the outcome of the study.

The historical range of negative controls was exceeded with metabolic activation in strains TA 98 (exp. 11)and TA 100 (exp. l), also the historical range of solvent controls was exceeded with metabolic activation in strain TA 100 (exp. I and II), Since these deviations are rather small, these effects are considered to be based upon biologically irrelevant fluctuations in the number of colonies and have no detrimental impact on the outcome of the study

The historical range of positive controls was exceeded without metabolic activation in strains TA 1535 (exp. 11)and TA 100 (exp. 11).This effect indicates the sensitivity of the strains rather than compromising the assay. Appropriate reference mutagens were used as positive controls. They showed a distinct increase in induced revertant colonies.

All acceptability criteria of the assay were met during the study.
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 with metabolic activation
negative without metabolic activation

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations by base pairchanges or frameshifts in the genome of the strains used. Therefore, ucb 6474 is considered to be non-mutagenic in this Bacterial Reverse Mutation Assay with Sa/mone//a fyphimurium strains TA 98, TA 100, TA 1535, and TA 1537, and the Escherichia coli strain WP2 uvrA.