Tellurium dioxide

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:

2012-05-8 to 2012-06-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tellurium dioxide

EC Number:

231-193-1

EC Name:

Tellurium dioxide

Cas Number:

7446-07-3

Molecular formula:

O2Te

IUPAC Name:

tellurium dioxide

Test material form:

solid: particulate/powder

Details on test material:

lot/batch No.of test material: EK1008F023

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9 mix; phenobarbital/β-naphthoflavone induced rat liver

Test concentrations with justification for top dose:

Range finding test: 5000; 2500; 1000; 316; 100; 31.6 and 10 μg/plate (TA 98 and TA 100 with and without metabolic activation)
Initial Test: 5000; 1581; 500; 158.1; 50; 15.81; 5 and 1.581 μg test item/plate
Confirmatory Test: 1581; 500; 158.1, 50; 15.81; 5; 1.581 and 0.5 μg test item/plate
Complementary Confirmatory Test: 5.81; 5; 1.581; 0.5; 0.1581; 0.05; 0.01581 and 0.005 μg test item/plate (TA1535; without metabolic activation)
Complementary Confirmatory Test: 5; 1.581; 0.5; 0.1581; 0.05; 0.01581; 0.005 and 0.001581 μg test item/plate (TA98, TA100 and TA1537 without metabolic activation)

Vehicle / solvent:

1 % (v/v) methyl cellulose solution was used
as vehicle to prepare the stock formulation of the test material. Test formulations were
freshly prepared at the beginning of the experiments in the testing laboratory by
diluting the stock formulation using the selected vehicle.

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

sodium azide

methylmethanesulfonate

other: 4-nitro-1,2-phenylenediamine (NPD); 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: Preliminary and initial experiment: in agar (plate incorporation)
For confirmatory and complementary confirmatory tests preincubation method was used

DURATION
- Preincubation period: 20 min
- Exposure duration: 48 h

SELECTION AGENT (mutation assays):

NUMBER OF REPLICATIONS: 3 plates/concentration

Evaluation criteria:

Criteria for Validity:
The study was considered valid if:
- the number of revertant colonies of the negative (vehicle/solvent) and positive controls were in the historical control range in all strains of the main tests;
- at least five analyzable concentrations were presented in all strains of the main tests.

Criteria for a Positive Response:
A test item was considered mutagenic if:
- a dose–related increase in the number of revertants occurred and/or;
- a reproducible biologically relevant positive response for at least one of the dose groups occurred in at least one strain with or without metabolic
activation.
An increase was considered biologically relevant if:
- in all strains: the number of reversion was more than twice higher than the reversion rate of the vehicle control.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Based on the results of the Preliminary Solubility Test, 1 % (v/v) methyl cellulose solution was selected for vehicle of the test item in the study. Concentrations of 5000; 2500; 1000; 316; 100; 31.6 and 10 μg/plate were examined in the Range Finding Test.

Based on the results of the Range Finding Test, the test item concentrations in the Initial Mutation Test were 5000; 1581; 500; 158.1; 50; 15.81; 5 and 1.581 μg test item/plate. Examined concentrations in the Confirmatory Mutation Test were 1581; 500; 158.1, 50; 15.81; 5; 1.581 and 0.5 μg test item/plate. Examined concentrations in the Complementary Confirmatory Mutation Test were 15.81; 5; 1.581; 0.5; 0.1581; 0.05; 0.01581 and 0.005 μg test item/plate (Salmonella typhimurium TA1535 strain without metabolic activation), and 5; 1.581; 0.5; 0.1581; 0.05; 0.01581; 0.005 and 0.001581 μg test item/plate (Salmonella typhimurium TA98, TA100 and TA1537 strains without metabolic activation).

 

In the Initial Mutation Test, Confirmatory Mutation Test and Complementary Confirmatory Mutation Test, none of the observed revertant colony numbers were above the respective biological threshold value. There were no consistent dose-related trends and no indication of any treatment effect. In all test item treated groups, the numbers of revertant colonies were below the biological relevance when compared with the solvent controls and were within the historical control range and were within the normal biological variability of the test system.

 

Inhibitory, cytotoxic effect of the test item was observed in the Initial Mutation Test in all tester strains with and without metabolic activation at the two or three highest concentration. Similar, but stronger cytotoxic effect was observed using the preincubation method (Confirmatory Mutation Test and Complementary Confirmatory Mutation Test) in all tester strains with and without metabolic activation.

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

In conclusion, the test item Tellurium dioxide had no mutagenic activity in the bacterium tester strains under the test conditions used in this study.

Executive summary:

In a reverse gene mutation assay in bacteria according to OECD guideline 471, strains TA 1535, TA 1537, TA98 and TA100 of S. typhimurium and E. coli WP2 uvrA were exposed to Tellurium dioxide, (powder 99.9 % a.i.), at concentrations up to 5000 µg/plate in the presence and absence of mammalian metabolic activation, (S9 mix; phenobarbital/β-naphthoflavone induced rat liver).

The initial Mutation Test was performed as plate incorporation method; the confirmatory and complementary assays were performed according to the pre-incubation method.

 

In the Initial Mutation Test, Confirmatory Mutation Test and Complementary Confirmatory Mutation Test, none of the observed revertant colony numbers were above the respective biological threshold value. There were no consistent dose-related trends and no indication of any treatment effect. In all test item treated groups, the numbers of revertant colonies were below the biological relevance when compared with the solvent controls and were within the historical control range and were within the normal biological variability of the test system.

 

Inhibitory, cytotoxic effect of the test item was observed in the Initial Mutation Test in all tester strains with and without metabolic activation at the two or three highest concentration. Similar, but stronger cytotoxic effect was observed using the preincubation method (Confirmatory Mutation Test and Complementary Confirmatory Mutation Test) in all tester strains with and without metabolic activation.

 

The mean values of revertant colonies of the solvent control plates were within the historical control range, the reference mutagens showed the expected increase in the number of revertant colonies, the viability of the bacterial cells was confirmed by a plating experiment in each test. At least five analyzable concentrations were presented in all strains of the main tests. The tests were considered to be valid.

 

 

In conclusion there was no evidence of induced mutant colonies over background.