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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro, cadmium telluride did not induce point mutations in S. typhimurium tester strains TA98, TA100, TA1535, TA1537, TA1538 and the E. coli strain WP2urvrA, both with and without metabolic activation. Cadmium telluride was negative in a chromosome aberration study with V79 hamster cells and in a gene mutation test using mouse lymphoma L5178Y cells.

Link to relevant study records

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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:
Not reported
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to
Guideline:
EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay
Target gene:
Not applicable
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2uvr A
Details on mammalian cell type (if applicable):
Not applicable

Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
15.81, 50, 158.1, 500, 1581 and 5000 µg/plate.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: 1% methylcellulose solution
- Justification for choice of solvent/vehicle: Because the test item is insoluble in any solvent compatible for the test system, using thickener was necessary to keep the test item particles in stable suspension. At 100 mg/mL concentration, homogeneous stable suspension was obtained using 1 % aqueous solution of methylcellulose as thickener.
Untreated negative controls:
yes
Remarks:
1% methylcellulose solution, DMSO, distilled water
Negative solvent / vehicle controls:
yes
Remarks:
methylcellulose solution, DMSO, distilled water
True negative controls:
no
Positive controls:
yes
Positive control substance:
no
Details on test system and experimental conditions:
METHOD OF APPLICATION: In agar (plate incorporation)

NUMBER OF REPLICATIONS: Triplicate
Evaluation criteria:
no information
Statistics:
Not available
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2
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:
none
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

None

Conclusions:
Interpretation of results (migrated information):
negative

The test material was considered to be non-mutagenic for all the used bacterial strains (Salmonella typhimurium as well as Escherichia coli) with as well as without metabolic activation
Executive summary:

A study was conducted to determine the potential mutagenicity of the test material using bacterial reverse mutation assay (Ames test). 

Four indicator Salmonella typhimurium strains TA98, TA100, TA1535 and TA 1537 and one indicator Escherichia coli WP2 uvrA strain were treated with fine suspensions of the test material using the plate incorporation method at doses of 15.81-5000 µg/plate).

Under the experimental conditions applied the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.

The test item Cadmium telluride had no mutagenic activity on the growth of the applied bacterium tester strains under the test conditions used in this study.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
5000, 4000, 3000, 2000, 1000, 500, 250 and 125 µg/mL (experiment without metabolic activation)
5000, 1666.7, 555.6, 185.2, 61.73, 20.58 and 6.86 µg/mL (experiment with metabolic activation).


Vehicle / solvent:
distilled water
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Remarks:
EMS and CP
Details on test system and experimental conditions:
Chromosome aberrations:

METHOD OF APPLICATION: in suspension

DURATION
- Preincubation period: 3 days
- Exposure duration: 20h (assay 1) and 28h (assay2)

SPINDLE INHIBITOR (cytogenetic assays): colchicine
STAIN (for cytogenetic assays): 5% Giemsa solution

NUMBER OF REPLICATIONS: two (per concentration and per assay)

NUMBER OF CELLS EVALUATED: at least 200 well-spread metaphase cells for each concentration (per assay). The examination of slides from a culture was halted when 15 or more metaphases with aberrations (excluding gaps) have been recorded for that culture

Evaluation criteria:
The test item is considered to have shown clastogenic activity in this study if all of the following criteria are met:
-Increases in the frequency of metaphases with aberrant chromosomes are observed at one or more test concentrations (only data without gaps will be considered).
-The increases are reproducible between replicate cultures and between tests (when treatment conditions were the same).
-The increases are statistically significant.
-The increases are not associated with large changes in pH or osmolarity of the treated cultures.

The historical control data for this laboratory were also considered in the evaluation. Evidence of a dose-response relationship (if any) was considered to support the conclusion.

The test item is concluded to have given a negative response if no reproducible, statistically significant increases are observed.
Statistics:
Fisher’s exact test
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: +S9: no, but tested up to precipitating conc; -S9: yes
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative

Chinese hamster V79 cells treated with cadmium telluride up to 5000 µg/mL did not show any consistent genotoxic activity under the conditions of this study
Executive summary:

The test item Cadmium telluride was tested for potential clastogenic activity using the Chromosome Aberration Assay. The study included two Concentration Selection Cytotoxicity Assays and two Chromosome Aberration Assays.

 

The performed experiments were considered to be valid and to reflect the real potential of the test item to cause structural chromosomal aberrations in the cultured V79 Chinese hamster cells used in this study.

 

Treatment with the test item did not result in a statistically and biologically significant, repeatable, dose-dependent increase in the frequency of the cells with structural chromosome aberrations without gaps either in the presence or absence of a metabolic activation system which was a cofactor-supplemented post-mitochondrial S9 fraction prepared from the livers of phenobarbital/b-naphthoflavone induced rats.


In conclusion, Cadmium telluride test item did not induce a significant level of chromosome aberrations in the performed experiments with or without metabolic activation.Therefore, Cadmium telluride is considered not clastogenic in this test system.

 

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
mammalian cell gene mutation assay
Target gene:
thymidine kinase gene
Species / strain / cell type:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:

Assay 1, 3-hour treatment with metabolic activation: 5000; 2500; 1250; 625; 312.5; 156.25 and 78.13 µg/mL
Assay 1, 3-hour treatment without metabolic activation: 5000; 4000; 3000; 2000; 1000; 500; 250; 125; 62.5 and 31.25 µg/mL
Assay 2, 3-hour treatment with metabolic activation: 5000; 2500; 1250; 625; 312.5; 156.25 and 78.13 µg/mL
Assay 2, 24-hour treatment without metabolic activation: 2000; 1750; 1500; 1250; 1000; 750; 500; 250; 125; 62.5 and 31.25 µg/mL µg/mL
Vehicle / solvent:
distilled water
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Remarks:
4-Nitroquinoline-N-oxide (NQO) and Cyclophosphamide monohydrate (CP)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: When cells were growing well, subcultures were established in an appropriate number of flasks (after thawing, the cells were subcultured no more than 5 times before used in the study).
- Exposure duration: In Assay 1, cells were treated for 3-hours in the presence and absence of S9 mix. In Assay 2, cells were treated for 3-hours in the presence of S9 mix and for 24-hours in the absence of S9 mix.

SELECTION AGENT (mutation assays): TFT (5-trifluorothymidine)

NUMBER OF REPLICATIONS: two per treatment

DETERMINATION OF CYTOTOXICITY
- Method: plating efficiency, Suspension Growth (SG) and Relative Total Growth (RTG)

Evaluation criteria:
The test item was considered to be mutagenic in this assay if all the following criteria were met :
1. The assay is valid.
2. Statistically significant (p < 0.05) and biologically relevant increases in mutation frequency are observed in treated cultures compared to the corresponding negative (vehicle) control values at one or more concentrations.
3. The increases in mutation frequency are reproducible between replicate cultures and/or between tests (under the same treatment conditions).
4. There is a significant concentration-relationship as indicated by the linear trend analysis (p < 0.05).
5. The mutation frequency at the test concentration showing the largest increase is at least 126 mutants per 106 viable cells (GEF = the Global Evaluation Factor) higher than the corresponding negative (vehicle) control value.
Statistics:
Dunnett’s test for multiple comparisons. T-test for independent samples.
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: mouse lymphoma L5178Y cells
Remarks:
Migrated from field 'Test system'.

The test item was examined up to 5000 µg/mL in the Preliminary Toxicity Test. Based on the results of the preliminary experiment, the following test item concentrations were examined in the mutation assays:

Assay 1, 3-hour treatment with metabolic activation: 5000; 2500; 1250; 625; 312.5; 156.25 and 78.13 µg/mL

Assay 1, 3-hour treatment without metabolic activation: 5000; 4000; 3000; 2000; 1000; 500; 250; 125; 62.5 and 31.25 µg/mL

Assay 2, 3-hour treatment with metabolic activation: 5000; 2500; 1250; 625; 312.5; 156.25 and 78.13 µg/mL

Assay 2, 24-hour treatment without metabolic activation: 2000; 1750; 1500; 1250; 1000; 750; 500; 250; 125; 62.5 and 31.25 µg/mL µg/mL

In Assays 1 and 2, insolubility was detected in the final treatment medium at the end of the treatment in some cases. There were no large changes in pH or osmolality after treatment.

In Assay 1, following a 3-hour treatment with metabolic activation, expressive cytotoxicity of the test item was observed at 5000 µg/mL concentration (relative total growth of 7%); therefore, this sample was excluded from the evaluation. An evaluation was made using data of the next concentration of 2500 µg/mL (relative total growth of 13 %) and five lower concentrations (a total of six samples). Significant increase in the mutation frequency was observed at2500 and 1250 µg/mLconcentrations; however, at 1250 µg/mLthe differencebetween the observed value and the relevant vehicle control value did not exceed the global evaluation factor, thus it was considered as biologically not relevant increase.

In Assay 1, following a 3-hour treatment without metabolic activation, excessive cytotoxicity of the test item was observed at 5000, 4000, 3000 and 2000 µg/mL concentrations, cells in these samples died during the treatment or in the expression period. Therefore, an evaluation was made using data of the first surviving concentration of 1000 µg/mL (relative total growth of 10%) and the next five concentrations (a total of six samples). Statistically significant increase in the mutation frequency was observed at1000 µg/mLconcentration.

In Assay 2, following a3-hour treatment with metabolic activation, no marked cytotoxicity of the test item was observed. An evaluation was made using data of the highest examined concentration of 5000 µg/mL (relative total growth of 44 %) and six lower concentrations (a total of seven samples). Statistically significantincrease in the mutation frequency was observed at 5000 µg/mL concentrations, but as the difference between the observed value and the relevant vehicle control value did not exceed the global evaluation factor, thus it was considered as biologically not relevant increase.

In Assay 2, following a 24-hour treatment without metabolic activation, excessive cytotoxicity of the test item was observed at 2000, 1750, 1500, 1250 and 1000 µg/mL concentrations, cells in these samples died during the treatment or in the expression period. The relative total growth value of the first surviving concentration of 500 µg/mL was 21 %. Therefore, an evaluation was made using data of all examined concentrations from 500 µg/mL to 31.25 µg/mL (a total of five samples). No statistically significant increases in the mutation frequency were observed at the evaluated concentrations.

The observed increases in the mutation frequency were examined for consistency through the study. The statistically and biologically significant increases detected in some cases Assay 1 were not repeatable in Assay 2. Furthermore, they appeared only at cytotoxic concentrations. The overall conclusion is that these small increases, present only where there was significant cytotoxicity, were not consistent, thus no clear mutagenic activity of the test item observed in the performed experiments.

The experiments were performed using appropriate untreated, negative (vehicle) and positive control samples in all cases. The spontaneous mutation frequency of the negative (vehicle) controls was in the recommended range in each test. The positive controls gave the anticipated increases in mutation frequency over the controls. The plating efficiencies for the negative (vehicle) controls at the end of the expression period were within the acceptable range in all assays. The evaluated concentration ranges were considered to be adequate, as they covered the range from cytotoxicity to no or little cytotoxicity or the recommended maximum concentration was the highest evaluated concentration. The number of test concentrations met the acceptance criteria. Therefore, the overall study was considered to be valid.

Conclusions:
Interpretation of results (migrated information):
negative

No clear mutagenic effect of Cadmium telluride (CdTe) was observed either in the presence or in the absence of metabolic activation system under the conditions of this Mouse Lymphoma Assay.
Executive summary:

The Mouse Lymphoma Assay with Cadmium telluride (CdTe) on L5178Y TK+/-3.7.2 C cells was considered to be valid and to reflect the real potential of the test item to cause mutations in the cultured mouse cells used in this study.

 

Treatment with the test item did result in a statistically significant increase in mutation frequencies in some cases in the presence or absence of a rat metabolic activation system (S9 fraction) in the Mouse Lymphoma Assay. However, they were not repeatable and appeared only where there was significant cytotoxicity. Therefore, they were considered not fulfilling all the criteria of a positive response, thus no clear mutagenic activity of the test item can be observed in the performed experiments.

 

In conclusion, no clear mutagenic effect of Cadmium telluride (CdTe) was observed either in the presence or in the absence of metabolic activation system under the conditions of this Mouse Lymphoma Assay.


 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the negative results from the Ames test and Mouse lymphoma test, cadmium telluride is considered to be non-mutagenic and based on the chromosome aberration test, it is considered as non-clastogenic. Overall, cadmium telluride is considered to be non-genotoxic. Therefore, no classification for mutagenicity is required.