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:
other information
Study period:
Feb to Mar 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported GLP Guideline conform study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
no bacteria strain included to detect cross-linking mutagens (e.g. TA 102)
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): ZK 10882
- Batch No.: 21502111, 21502112

Method

Target gene:
Histidine gene locus
Species / strain
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100
Metabolic activation:
with and without
Metabolic activation system:
liver S9-mix from Aroclor 1254 -treated rats
Test concentrations with justification for top dose:
6-Chlor-Chlormethyldien: six concentrations from 0.005 to 0.5 mg/plate
9-Acridinamine, hydrochloride: 100 µg/plate
2-Aminoanthracene: 2.0 µg/plate
2-Nitrofluorene: 10 µg/plate
Benzo[a]pyrene: 5 µg and 10.0 µg/plate
Sodium azide: 5 µg/plate
Cyclophosphamide: 400 µg/plate



Controls
Solvent controls:
yes
Remarks:
DMSO and phosphate buffer pH 7.4, 0.1 mol/l
Positive controls:
yes
Positive control substance:
other: 9-Acridinamine, hydrochloride; 2-Aminoanthracene; 2-Nitrofluorene; Benzo[a]pyrene; Sodium azide; Cyclophosphamide

Results and discussion

Test results
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no, but tested up to precipitating concentrations
Vehicle controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

There were visible precipitates in the agar starting from 0.05 mg/plate in all tested strains in absence and presence of S9 mix.

Applicant's summary and conclusion

Executive summary:

6 -Chlor-Chlormethyldien (ZK 10882) was examined for mutagenic activity up to 500 µg/plate in the five histidine-dependent Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98 with and without metabolic activation.

No cytotoxic effect was observed up to 0.5 mg/plate with and without S9 mix. There were visible precipitates in the agar from 0.05 mg/plate onwards with and without S9 mix in all tested strains.

There was no evidence for a mutagenic activity of 6 -Chlor-Chlormethyldien, when tested up to the precipitating dose level of 0.5 mg/plate in the absence and presence of S9 mix.