Tetraamminepalladium(2+) dinitrate

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:

9 February-10 April 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP, on closely-related surrogate. Astrain capable of detecting certain oxidising mutagens and/or cross-linking agents, for example TA102, was not included.

Justification for type of information:

Tetraamminepalladium hydrogen carbonate is considered to fall within the scope of the read-across category "tetraamminepalladium salts". See IUCLID section 13 for full read-across justification report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Astrain capable of detecting certain oxidising mutagens and/or cross-linking agents, for example TA102, was not included.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Astrain capable of detecting certain oxidising mutagens and/or cross-linking agents, for example TA102, was not included.

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tetramminepalladium (II) hydrogen carbonate

IUPAC Name:

Tetramminepalladium (II) hydrogen carbonate

Constituent 2

Reference substance name:

134620-00-1

Cas Number:

134620-00-1

IUPAC Name:

134620-00-1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Tetrammine palladium hydrogen carbonate
- Substance type: No data
- Physical state: pale yellow powder
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: No data
- Lot/batch No.: DD0247
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: room temperature

Method

Target gene:

Histidine

Species / strain

Species / strain 1

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Rat liver homogenate metabolising system (S9)

Test concentrations with justification for top dose:

0, 50, 150, 500, 1500 and 5000 µg/plate in preliminary cytotoxicity test
0, 0.15 (Expt 1 only), 0.5, 1.5, 5, 15, 50 (-S9)
0, 1.5, 5, 15, 50, 150, 500 (Expt 1 only) (+S9)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Sterile distilled water
- Justification for choice of solvent/vehicle: Test guideline recommends use of aqueous solvent wherever possible

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

80 µg/plate for TA 1537 without S9

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

0.2 µg/plate for TA 98 without S9

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenyl enediamine

Remarks:

5 µg/plate for TA 1538 without S9

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

3 and 5 µg/plate for TA 100 and 1535 respectively (both without S9)

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

1, 2, 0.5, 0.5 and 2 µg/plate for TA 100, 1535, 1538, 98 and 1537 strains respectively (all with S9)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: Not applicable
- Exposure duration: 48 hours
- Expression time (cells in growth medium): Not applicable
- Selection time (if incubation with a selection agent): Not applicable
- Fixation time (start of exposure up to fixation or harvest of cells): Not applicable

SELECTION AGENT (mutation assays): Not applicable
SPINDLE INHIBITOR (cytogenetic assays): Not applicable
STAIN (for cytogenetic assays): Not applicable

NUMBER OF REPLICATIONS: 3 (Experiment carried out twice)

NUMBER OF CELLS EVALUATED: Not applicable

DETERMINATION OF CYTOTOXICITY
- Method: Reduction in no. of revertant colonies/thining of background lawn

OTHER EXAMINATIONS:
- Determination of polyploidy: Not applicable
- Determination of endoreplication: Not applicable

Evaluation criteria:

Positive results should have a dose-related and statistically significant increase in mutation rate in one or more bacterial strains with or without S9. To be considered negative, the number of induced revertants should be less than twofold compared to spontaneous revertants (controls).

Statistics:

No data

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

Remarks:

The test material caused a visible reduction in the growth of the bacterial lawn at 50 and 150 µg/plate and above for tester strains without and with metabolic activation respectively

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The test material caused a visible reduction in the growth of the bacterial lawn at 50 and 150 µg/plate and above for tester strains without and with metabolic activation respectively

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The test material caused a visible reduction in the growth of the bacterial lawn at 50 and 150 µg/plate and above for tester strains without and with metabolic activation respectively

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The test material caused a visible reduction in the growth of the bacterial lawn at 50 and 150 µg/plate and above for tester strains without and with metabolic activation respectively

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The test material caused a visible reduction in the growth of the bacterial lawn at 50 and 150 µg/plate and above for tester strains without and with metabolic activation respectively

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data
- Effects of osmolality: No data
- Evaporation from medium: No data
- Water solubility: No data
- Precipitation: No data
- Other confounding effects: No data

RANGE-FINDING/SCREENING STUDIES: The dose range used was 0, 50, 150, 500, 1500 and 5000 µg/plate

COMPARISON WITH HISTORICAL CONTROL DATA: No data

ADDITIONAL INFORMATION ON CYTOTOXICITY: The test material caused a visible reduction in the growth of the bacterial lawn at 50 and 150 µg/plate and above for tester strains without and with metabolic activation respectively

Remarks on result:

other: strain/cell type: TA 100

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

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

In a guideline study, to GLP, tetraamminepalladium hydrogen carbonate was not mutagenic in a bacterial reverse mutation (Ames) assay using five Salmonella typhimurium strains (TA 98, TA100, TA1535, TA1537 and TA1538), when tested at up to cytotoxic concentrations in the presence and absence of a rat liver metabolic activation (S9) system.

Executive summary:

Tetraamminepalladium hydrogen carbonate was assessed for potential mutagenic activity in a bacterial reverse mutation (Ames) assay, conducted according to OECD Test Guideline 471, and to GLP. The test compound was tested in five strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537 and TA1538). (However, a strain capable of detecting cross-linking mutagens, for example TA102, was not included.)

 

The dose ranges were determined in a preliminary assay for cytotoxicity and were 0.15-50 and 1.5-500 µg/plate with and without the addition of a rat liver homogenate metabolising (S9) system. All assays were carried out in triplicate, at up to 50 and 500 µg/plate in the absence and presence of S9, respectively. The experiment was repeated.

 

Tetraamminepalladium hydrogen carbonate showed no evidence of a dose-related increase in revertant frequency at any dose levels in any each strain, either in the presence or absence of S9.