Tungsten dioxide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Data was taken directly from NTP website. A full study report was not available for review. Three bacterial strains were used. Five concentrations plus controls were evaluated. Assay was conducted both with and without metabolic activation. Due to similar physical-chemical properties, similar or lower transformation/dissolution results and similar or lower in vitro bioaccessibility in synthetic body fluids for tungsten dioxide (the target substance) than the source substances, the resulting toxicity potential would also be expected to be similar or lower, so read-across is appropriate. Therefore, the dose descriptors are expected to be sufficiently similar or higher for the target substance, and read-across to the source chemical is adequately protective. For more details refer to the attached description of the read-across approach.

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Tungsten trioxide
Target: Tungsten Dioxide
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Data source

Reference

Reference Type:

grey literature

Title:

Unnamed

Year:

2005

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

3 bacterial strains were used, while 5 are recommended. 2-aminoanthracene should not be used as sole indicator of the efficacy of S-9. Each batch of S-9 should be characterized with a mutagen that requires metabolic activation by microsomal enzymes.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tungsten trioxide

EC Number:

215-231-4

EC Name:

Tungsten trioxide

Cas Number:

1314-35-8

Molecular formula:

O3W

IUPAC Name:

trioxotungsten

Details on test material:

- Name of test material (as cited in study report): Tungsten trioxide

Method

Target gene:

histidine locus

Species / strain

Species / strain 1

Species / strain / cell type:

E. coli WP2 uvr A pKM 101

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 100

Species / strain 3

Species / strain / cell type:

S. typhimurium TA 98

Metabolic activation:

with and without

Metabolic activation system:

male Sprague Dawley rat liver S9

Test concentrations with justification for top dose:

0, 100, 500, 1000, 5000, 10000 µg/plate

Vehicle / solvent:

water

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

water

True negative controls:

no

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

without activation Migrated to IUCLID6: Used with E. coli WP2 uvr A pKM 101 strain

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene (or occasionally, sterigmatocystin) was used with strains E. coli WP2 uvr A pKM 101, S. typhimurium TA98 and TA100

Remarks:

with activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

Evaluation criteria:

Means and standard deviations were calculated for the number of mutants in every concentration group.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

In a reverse gene mutation assay in bacteria, strains TA98, TA100 of S. Typhimurium and E. coli pKM101 were exposed to Tungsten trioxide up to a limit concentration of 10.000 µg/plate in the presence and absence of mammalian metabolic activation (S9). 
The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background. This study is classified as acceptable. This study satisfies the basic requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data but deviates in the following: 3 bacterial strains were used, while 5 are recommended. 2-aminoanthracene should not be used as sole indicator of the efficacy of S-9. Each batch of S-9 should be characterized with a mutagen that requires metabolic activation by microsomal enzymes.

According to the results of the study, Tungsten trioxide was non-mutagenic in the Ames test with Salmonella tester strains TA98, TA100 and E. coli pKM101 up to 10000 ug/plate in the presence and absence of metabolic activation.

Executive summary:

No in vitro genotoxicity data of sufficient quality are available for tungsten dioxide (target substance). However, in vitro genotoxicity data are available for tungsten trioxide (source substance), which will be used for read-across. Due to lower water solubility and lower toxicity for the target substance compared to the source substance, the resulting read-across from the source substance to the target substance is appropriate as a conservative estimate of potential toxicity for this endpoint. In addition, read-across is appropriate because the classification and labelling is more protective for the source substance than the target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, lower for the source substance. For more details, refer to the read-across category approach included in the Category section of this IUCLID submission and/or as an Annex in the CSR.