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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
Study period:
February 28, 1990 - April 3, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Performed in accordance with OECD 471 and GLP principles. But the report does not contain the laboratory historical control data of the vehicle and of the strain-specific positive controls. Also the doses of the test substance were tested in duplicate in each strain in the preliminary study, without a justification.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
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): m-xylylene diisocyanate
- Physical state: liquid

Method

Target gene:
- S. typhimurium: Histidine gene
- E. coli: Tryptophan gene
Species / strainopen allclose all
Species / strain:
other: TA100, TA1535, TA98, TA1537 and TA1538
Metabolic activation:
with and without
Metabolic activation system:
Rat liver S9-mix induced by a combination of phenobarbital and 5,6-benzoflavone
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
Rat liver S9-mix induced by a combination of phenobarbital and 5,6-benzoflavone
Test concentrations with justification for top dose:
Preliminary test (without and with S9-mix):
S. typhimurium TA100, TA1535, TA98, TA1537, TA1538 and E. coli WP2 uvr A: 50, 100, 500, 1000 and 5000 µg/plate

Main study:
Without and with S9-mix:
S. typhimurium TA100, TA1535 and E. coli WP2 uvr A: 125, 250, 500, 1000, 2000 and 4000 µg/plate
Without S9-mix:
S. typhimurium TA98, TA1537 and TA1538: 63, 125, 250, 500 and 1000 µg/plate
With S9-mix:
S. typhimurium TA98, TA1537 and TA1538: 125, 250, 500, 1000, 2000 and 4000 µg/plate

Experiment 2:
Without and with S9-mix:
S. typhimurium TA100, TA1535 and E. coli WP2 uvr A: 125, 250, 500, 1000, 2000 and 4000 µg/plate
Without S9-mix:
S. typhimurium TA98, TA1537 and TA1538: 63, 125, 250, 500 and 1000 µg/plate
With S9-mix:
S. typhimurium TA98, TA1537 and TA1538: 125, 250, 500, 1000, 2000 and 4000 µg/plate
Vehicle:
- Vehicle(s)/solvent(s) used: DMSO
Controls
Negative controls:
no
Solvent controls:
yes
Positive controls:
yes
Positive control substance:
other: see section "Any other information on materials and methods inc. tables"
Details on test system and conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS:
- Preliminary study: doses of the test substance were tested in duplicate in each strain
- Main study: doses of the test substance were tested in triplicate in each strain. Two independent experiments were conducted.

NUMBER OF CELLS EVALUATED: 10E8 per plate

Evaluation criteria:
Non parametric multiple range test (Ryan) was employed for analyzing the data. A reproducible and statistical significant dose related increase in revertant colonies for at least 1 strain is considered positive.

Results and discussion

Test resultsopen allclose all
Species / strain:
other: TA100, TA1535, TA98, TA1537 and TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Remarks:
(starting at 2000 µg/plate)
Vehicle controls valid:
yes
Positive controls valid:
yes
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Remarks:
(starting at 2000 µg/plate)
Vehicle controls valid:
yes
Positive controls valid:
yes
Additional information on results:
COMPARISON WITH HISTORICAL CONTROL DATA: No data

Any other information on results incl. tables

Mutagenic response of XDI in the Salmonella typhimurium reverse mutation assay and the Escherichia coli reverse mutation assay: see the attached background information.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

All bacterial strains showed negative responses over the entire dose range, i.e. no significant dose-related increase in the number of revertants in two independently repeated experiments. It is concluded that this test is valid and that the substance is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.
Executive summary:

The genetic toxicity of the substance was assessed at concentrations of 4000 µg/plate using S. typhimurium TA100, TA1535, TA98, TA1537, TA1538 and E. coli WP2 uvr A strains. All bacterial strains showed negative responses with and without metabolic activation.