Registration Dossier

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:
2004
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The chemical intermediate CD 616 BS was investigated in a modified bacterial reversemutation test as described by Ames et al. (1975). The traditional Salmonella microsomemutation assay (Ames test) is used extensively as a routine test for mutagenicity for morethan 25 years. The high throughput microtitre-based version, called Ames II, is based onthe same genetic principle (base-pair substitution and frameshift mutations in the hisoperon of S. typhimurium) as the traditional Ames test but combined with the fluctuationmethod (Gee et al., 1998). Because of its high concordance (80%) compared with thestandard assay, the Ames II procedure seems an effective screen for identifying bacterialmutagens (Flueckiger et al., 2004).
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Species / strain
Species / strain / cell type:
other: TA 7001, TA 7002, TA 7003, TA 7004, TA 7005, TA 7006 and TA 98
Test concentrations with justification for top dose:
1 to 2500 μg/mL
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
2-nitrofluorene
other: 2-aminoanthracene

Results and discussion

Test results
Species / strain:
other: TA 7001, TA 7002, TA 7003, TA 7004, TA 7005, TA 7006 and TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
No bacteriotoxicity was seen up to 2500 μg/mL
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
CD 616 BS precipitated at concentrations ≥500 μg/mL in the medium

Applicant's summary and conclusion

Conclusions:
Based on the described results it is concluded, that CD 616 BS, when tested up to insoluble concentrations, caused neither base-pair substitutions nor frameshift mutations in bacteria. No evidence of genotoxic activity was observed in a series of S. typhimurium tester strains (TA Mix and TA 98) in the absence and presence of metabolic activation. The test article is, therefore, classified as "Ames II negative".