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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:
From Feb. 10, 1986 to Feb. 14, 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
No additional analyses of the composition and stability of the test sample in the solvent or test system were performed
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
- Name of test material (as cited in study report): m-Tetramethylxylene Diisocyanate (m-TMXDI)
- Physical state: Clear, non-viscous liquid
- Analytical purity: 98 %
- Density: 1.05 g/mL
- Storage condition of test material: Stored under nitrogen at room temperature

Method

Target gene:
Not applicable
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell type (if applicable):
not applicable
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Details on mammalian cell type (if applicable):
not applicable
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Aroclor-1254 induced, rat-liver homogenate (S9
Test concentrations with justification for top dose:
Preliminary Toxicity study: 0.001, 0.003, 0.01, 0.03, 1, 3, 5 and 10 mg/plate
Definitive study: 0.0003, 0.001, 0.003, 0.01 and 0.03 mg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: Test material was soluble in acetone
Controls
Untreated negative controls:
yes
Remarks:
Acetone
Negative solvent / vehicle controls:
yes
Remarks:
Acetone
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 4-nitro-o-phenylenediamine, 9-aminoacridine, sodium azide and 2-aminoanthracene
Remarks:
with and without metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)


DURATION
- Expression time: 48-72 h


NUMBER OF REPLICATIONS: Three


DETERMINATION OF CYTOTOXICITY
- Method: Growth inhibition of the background lawn or a reduction in the number of spontaneous mutants
Evaluation criteria:
If the mean number of revertant colonies was not increased to two or three times higher than the concurrent solvent control value, then the test chemical was not considered to be a bacterial mutagen.
Statistics:
No data

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
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
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES: Test chemical at concentration range of 0.001-10 mg/plate was evaluated for cytotoxicity using strain TA100. Toxicity assessed at 24-48 h by observations for either growth inhibition of the backgroud lawn or a reduction in the number of spontaneous mutants.


COMPARISON WITH HISTORICAL CONTROL DATA: Yes


ADDITIONAL INFORMATION ON CYTOTOXICITY:
Cytotoxicity in the definitive test was defined as either a reduction in the number of revertant colonies or an inhibition of growth of the background lawn.
- In the test without metabolic activation, dose-related toxicity was observed in all strains except TA1535 at 0.03 mg /plate.
- In the test with metabolic activation, some degree of toxicity was observed at 0.03 mg/plate with all strains except TA98 and TA1535.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Preliminary study: Test material at concentration of 0.03 mg/plate allowed only sparse growth of the background lawn while a slightly higher dose of 0.1 mg/plate and higher dose levels produced complete absence of the background lawn and were considered to be cytotoxic.

Applicant's summary and conclusion

Conclusions:
Under the test conditions, the test material was considered to be non-mutagenic in the Salmonella/microsome bacterial mutagenicity assay.

Executive summary:

A study was conducted to evaluate the potential mutagenic activity of the test substance using the Salmonella/microsome bacterial mutagenicity assay (Ames test). The study was conducted according to OECD Guideline 471, in compliance with GLP. Test doses were chosen from the data obtained in a preliminary study which indicated that a concentration of 0.03 mg/plate allowed only sparse growth of the background lawn while 0.1 mg/plate and higher dose levels produced complete absence of the background lawn and were considered to be cytotoxic. The test substance was studied with and without metabolic activation using triplicate cultures at concentration range of 0.03-0.0003 mg/plate. Mutagenic activity was not observed with any of the five bacterial strains (S. typhimurium TA 1538, 1535, TA 1537, TA 98 and TA 100) with or without metabolic activation. Under the test conditions, the test substance was considered to be non-mutagenic in the Salmonella/microsome bacterial mutagenicity assay (Guzzie and Morabit, 1986).