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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Meets generally accepted scientific standards, well documented and acceptable for assessment - Follow-up study to BASF AG 40M0425/904274, investigating the ability of the test substance to cause mutations in one strain (TA 98) in the presence of Norharman.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1990

Materials and methods

Principles of method if other than guideline:
In a standard plate test, the ability of the test substance to induce frameshift mutations in S. typhimurium strain TA 98 in the presence of Norharman and metabolic activation was investigated.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
Histidine operon
Species / strain
Species / strain / cell type:
S. typhimurium TA 98
Metabolic activation:
with
Metabolic activation system:
1 part of induced rat liver S-9 fraction mixed with 9 parts of cofactors (MgCl2, KCl, Glu-6-p, NADP, phosphate buffer (NaH2PO4, Na2HPO2.2H2O) (1:9)
Test concentrations with justification for top dose:
- Test substance: 20, 100, 500, 2500, 5,000 µg/plate.- 200 µg/plate Norharman was added to each culture.
Vehicle / solvent:
- Vehicle: DMSO.- Justification for choice of vehicle: no data.
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Anilin
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation test) - 200 µg/plate Norharman was added to each culture.DURATION- Exposure duration: 48 hours at 37°C.NUMBER OF REPLICATIONS: 1 experiment; 3 cultures/experiment.DETERMINATION OF CYTOTOXICITY - Method: reduction in the number of spontaneous revertants or a clearing of the bacterial background lawn.
Evaluation criteria:
In general, a test chemical is considered positive if the following criteria are met:- Doubling of the spontaneous mutation rate (control).- Dose-response relationship.- Reproducibility of the results
Statistics:
No statistical evaluation needed be performed.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS- Precipitation: Precipitation of the test item was observed at 5,000 µg/plate only.RANGE-FINDING/SCREENING STUDIES:- no data
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Summary of results (TA 98), with metabolic activation.

      TA 98
  Concentration (µg/plate) S9 X (n=4) revertant factor
test subst. control yes 30  
20 yes 37 1.2
100 yes 37 1.2
500 yes 29 1.0
2,500 yes 35 1.2
5,000 yes 19* 0.6
         
l control yes 30  
  positive control yes 90 3.0

* precipitation

Applicant's summary and conclusion