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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 September 1983 to 3 October 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1984

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Method

Target gene:
Histidine dependence
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Metabolic activation:
with and without
Metabolic activation system:
S-9 mix
Test concentrations with justification for top dose:
0, 40, 200, 1000 and 5000 µg/plate.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
no
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-acetylaminofluorene
sodium azide
other: 4-nitro-o-phenylene diamine, 2-amino-anthracene, Neutral Red,
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: five at each dose level and ten for the solvent controls

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
other: TA1535, TA1537, TA98 & TA100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
The top concentration of 5,000 µg/plate precipitated in the top agar. The revertant colony counts per plate are summarised in Table 1. No increases in revertant colony numbers were observed after treatment of any of the five tested strains with the test material, either in the presence or absence of rat liver microsomal fraction.

Any other information on results incl. tables

Table 1: Mean revertant colony counts per plate

     Strain of Salmonella typhimurium
 Concentration (µg/plate)  Metabolic activation  TA1535  TA1537  TA1538  TA98  TA100
 5000  -  **  **  **  **  **
 1000  -  20  5  12  13  63
 200  -  14  4  9  13  81
 40  -  14  7  11  14  77
 0  -  13  6  13  16  84
 5000  +  **  **  **  **  **
 1000  +  13  3  9  13  50
 200  +  14  5  12  13  69
 40  +  6  6 14  23  72
 0  +  11  8  17  20  76

- absence of metabolic activation

+ presence of metabolic activation

** test material precipitated in top agar

Applicant's summary and conclusion

Conclusions:
Under the conditions of the test, the test material was determined to be negative in a bacterial gene mutation assay.
Executive summary:

A non-GLP compliant bacterial gene mutation assay was conducted in line with sound scientific principles similar to OECD 471 and EU Method B13/14.

No increases in revertant colony numbers were observed after treatment of any of the five tested strains with the test material, either in the presence or absence of rat liver microsomal fraction.

Under the conditions of the test, the test material was determined to be negative in a bacterial gene mutation assay.