4,4'-ethylidenediphenyl dicyanate

Genetic toxicity: in vitro

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:

October 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, GLP-compliant

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Test material form:

other: amber liquid

Details on test material:

- Name of test material: HTP-103
- Physical state: light yellow liquid
- Lot/batch No.: 87A006P251, received at IRI on 23 November 1988
- Stability under test conditions: stable
- Storage condition of test material: in the dark under ambient conditions

Method

Species / strain

Species / strain / cell type:

other: Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S-9-mix

Test concentrations with justification for top dose:

Toxicity Test:
A toxicity test using strain TA 100 only was performed in the presence and absence of S9 mix to establish suitable dose levels for the mutation tests. One plate of each of the following concentrations of HPT-103 was used:
33, 100, 333, 1000, 3333 and 10000 ug per plate

Main Tests:
Two Independent mutation tests were conducted using 5 bacterial strains (TA 1535, TA 1537, TA 1538, TA 98 and TA 100).
The dose levels used in the first of these experiments, and selected on the basis of the results of the toxicity test, were 3, 10, 33, 100, 333 and 1000 ug per plate in the presence of S9 mix. Dose levels used in the absence of S9 mix were 1, 3, 10, 33, 100 and 333 ug per plate.
The dose levels used in the second of these experiments and selected on the basis of the results of the first experiment were:
3, 10, 33, 100, 333 and 1000 ug per plate (TA 1535 and TA 100 in the presence of S9 mix)
1, 3, 10, 33, 100 and 333 ug per plate (TA 1537, TA 1538 and TA 98 in the presence of S9 mix; TA 1535 and TA 100 in the absence of S9 mix)
0.3, 1, 3, 10, 33 and 100 ug per plate (TA 1537, TA 1538 and TA 98 in the absence of S9 mix)
A further test was carried out since TA 100 in the presence of S9 mix in Experiment 2 was unaccetable. This test was done exactly as in Experiment 2. Triplicate plates were prepared for each bacterial strain and dose level in both the presence and absence of S9 mix.

Vehicle / solvent:

Dimethylsulfoxide

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

other: 2-aminoanthracene

Remarks:

2-aminoanthracene used with S9-mix; sodium azide, 2-nitrofluorene and 9-aminoacridine used without S9-mix

Results and discussion

Test results

Test results 1

Species / strain:

other: Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

(>= 100 ug/plate)

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Species / strain:

other: Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, TA 1538

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

(>= 33 ug/plate)

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: other: main test

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Precipitation was apparent only at the highest concentration (1000 ug per plate).

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

The substance can be considered as non-mutagenic in this Ames test.

Executive summary:

The reverse mutation assay was performed according to EU-test method B.13/14 with 5 Salm. typh. strains (TA98, TA100; TA1535, TA1537, TA1538) with and without metabolic activation. Tested concentrations ranged from 0.3 up to 1000 ug/plate. Metabolic activation system was Aroclor-induced rat liver S-9-mix. The test item was found to be non-mutagenic in this study.