Palladium sulphate

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:

21 February 2008 to 13 March 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD, Japan)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

1

Reference substance name:

Palladium (II) sulphate

Cas Number:

13566-03-5

IUPAC Name:

Palladium (II) sulphate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): palladium (II) sulphate hydrate
- Substance type: brown powdery solid
- Physical state: solid
- Analytical purity: > 99%
- Impurities (identity and concentrations): < 1%
- Purity test date: no data
- Lot/batch No.: HL4050631
- Expiration date of the lot/batch: no data
- Stability under test conditions: hygroscopic, avoid direct sunlight
- Storage condition of test material: room temperature, under dry (dehumidified) conditions
- Other:

Method

Target gene:

Histidine for S. typhimurium strains; tryptophan for E.coli WP2 uvrA

Species / strain

Species / strain 1

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S9, microsomal fraction derived from phenobarbital- and 5,6-benzoflavone-induced rat liver

Test concentrations with justification for top dose:

2.4, 4.9, 10, 20, 39 or 78 μg/plate in tests without S9
10, 20, 39, 78, 156 or 313 μg/plate in tests with S9
(These concentrations were selected after a preliminary test using doses of 1.2, 4.9, 20, 78, 313, 1250 or 5000 μg/plate showed that growth inhibition occurred at and above 78 and 313 μg/plate, respectively without and with S9)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: dehydrated DMSO
- Justification for choice of solvent/vehicle: at request of sponsor and after solubility tests

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

5.0 μg/plate for TA1537, TA98 and TA100 with S9

Controls 2

Positive control substance:

sodium azide

Remarks:

0.5 μg/plate for TA1535 without S9

Controls 3

Positive control substance:

other: 2-aminofluorene

Remarks:

0.01 μg/plate for TA100 and E. coli WP2 uvrA and 0.1 μg/plate for TA98 without S9

Controls 4

Positive control substance:

other: 2-aminoanthracene

Remarks:

2.0 μg/plate for TA1535 and 10 μg/plate for E. coliWP2 uvrA with S9

Controls 5

Positive control substance:

other: ICR-191

Remarks:

1.0 μg/plate for TA1537 without S9

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

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

NUMBER OF REPLICATIONS: plates prepared in triplicate; duplicate studies carried out.

OTHER: The preparations of the test solutions and the study procedures were conducted under lamps with ultraviolet light absorbent filters.

Evaluation criteria:

The test substance was considered to demonstrate mutagenic activity if the number of revertant colonies was at least double that of the spontaneous mutants on the control plates and showed a reproducible dose-response.

Results and discussion

Test results

Test results 1

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 78 μg/plate without S9 for all strains and at 156 and 313 μg/plate with S9

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 78 μg/plate without S9 for all strains and at 156 and 313 μg/plate with S9

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: a preliminary test showed cytotoxicity at and above 78 and 313 μg/plate, respectively without and with S9. No increase in mutation frequency was observed with the test substance

COMPARISON WITH HISTORICAL CONTROL DATA: no data given in the report but the frequency of spontaneous revertants are within the ranges given in the literature. Mutation frequency for the positive control substances were reported to be within the historic range

ADDITIONAL INFORMATION ON CYTOTOXICITY:

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Palladium (II) sulphate hydrate did not cause an increase in mutation frequency when tested at up to the limits of cytotoxicity, either with or without S9, in a guideline (GLP) bacterial reverse mutagenicity assay.

Executive summary:

In a OECD Test Guideline 471 study, to GLP, the mutagenic potential of palladium (II) sulphate hydrate was assessed in a reverse mutagenicity assay (Ames test) using the S. typhimurium strains TA1535, TA1537, TA98 and TA100 and E. coli WP2 uvrA.

 

Two independent experiments (each in triplicate) were carried out using the preincubation method, both with and without S9. A preliminary range-finding study had shown the test substance to be cytotoxic at doses at and above 78 and 313 μg/plate, respectively, without and with S9. In consequence these were the top doses tested.

 

Palladium (II) sulphate hydrate did not cause an increase in mutation in these studies, either with or without S9. In contrast, the known mutagens used as positive controls showed the expected mutagenic activity.