Palladium (II) di(4-oxopent-2-en-2-oate)

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:

28 June - 22 October 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study, to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Minor study deviation did not affect overall interpretation of study findings or compromise integrity of the study

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Palladium di(4-oxopent-2-en-2-oate)

IUPAC Name:

Palladium di(4-oxopent-2-en-2-oate)

Constituent 2

Reference substance name:

Palladium (II) di(4-oxopent-2-en-2-oate)

EC Number:

237-859-8

EC Name:

Palladium (II) di(4-oxopent-2-en-2-oate)

Cas Number:

14024-61-4

Molecular formula:

C10H14O4Pd

IUPAC Name:

Palladium (II) di(4-oxopent-2-en-2-oate)

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) di(4-oxopent-2-en-2-oate)
- Physical state: Solid
- Analytical purity: 100%
- Impurities (identity and concentrations): Not applicable
- Composition of test material, percentage of components: Palladium 34.98%
- Isomers composition: Not applicable
- Purity test date: 29 May 2013
- Lot/batch No.: 21613
- Expiration date of the lot/batch: June 2014
- Stability under test conditions: Not identified
- Storage condition of test material: 15-25 deg C, protected from light, under nitrogen and in tightly closed container

Method

Target gene:

Histidine.

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

mammalian liver post-mitochondrial fraction (S9)

Test concentrations with justification for top dose:

Range-Finder (TA98; TA100; TA102 only):
0, 5, 15.81, 50, 158.1, 500, 1581, 5000 ug/plate (with and without S9)

Expt1
0, 0.1581 (without S9 only), 0.5, 1.581, 5, 15.81, 50, 158.1 ug/plate (with and without S9), 500 ug/plate (with S9 only)

Expt2
0, 1.563 (without S9 only), 3.125, 6.25, 12.5, 25, 50 ug/plate (with and without S9), 100 ug/plate (with S9 only)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: dimethyl formamide.

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

benzo(a)pyrene

mitomycin C

other: 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation). In the presence of S9 in experiment 2, there is also a pre-incubation step.

DURATION
- Preincubation period: 20 minutes
- Exposure duration: 3 days

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: Background lawns examined.

Evaluation criteria:

An increase in revertant numbers that give a significant response which was concentration-related.

A positive trend/effect described are reproducible.

The test article was considered positive in this assay if all the above criteria are met.

Statistics:

Dunnett's test was used to compare the counts at each concentration with the controls.

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: The concentrations tested in the Ames test were determined in a preliminary cytotoxicity range-finder experiment.

COMPARISON WITH HISTORICAL CONTROL DATA: The number of revertants in negative (vehicle) and positive controls fell within the 99% confidence intervals of the current observed historial ranges.

Remarks on result:

no mutagenic potential (based on QSAR/QSPR prediction)

Applicant's summary and conclusion

Conclusions:

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

In a bacterial reverse mutation (Ames) test, conducted according to OECD Test Guideline 471 and to GLP, palladium di(4-oxopent-2-en-2-oate) failed to induce an increase in mutation frequency in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of Salmonella typhimurium when tested at concentrations of up to 5000 μg/plate or up to the limit of cytotoxicity, in the absence and presence of S9.

Executive summary:

Palladium di(4-oxopent-2-en-2-oate) was tested in a bacterial reverse mutation (Ames) assay, conducted according to OECD Test Guideline 471 and to GLP. The test substance was assayed in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of Salmonella typhimurium, both in the absence and in the presence of metabolic activation by an Aroclor 1254-induced rat liver post-mitochondrial fraction (S9), in two separate experiments. The highest concentrations of test article analysed were limited by toxicity and were determined following a preliminary toxicity range-finder experiment.

In experiment 1, cells were treated with the test article at a maximum concentration of 158.1 µg/plate in the absence of S9, and 500 µg/plate in the presence of S9. Following these treatments, evidence of toxicity was observed in all strains at 15.81 µg/plate and above in the absence of S9 and at 50 µg/plate and above in the presence of S9.

In experiment 2, the maximum concentration was reduced to 50 µg/plate for all treatments in the absence of S9, and 100 µg/plate for treatments in the presence of S-9 based on toxicity observed in Experiment 1. All treatments in the presence of S9 were further modified by the inclusion of a pre-incubation step.

Appropriate vehicle and positive control cultures were included in the test system under each treatment condition and fit the acceptance criteria. Following palladium di(4-oxopent-2-en-2-oate) treatments of all the test strains in the absence and presence of S9, no statistically significant increases in revertant numbers were observed when the data were analysed at the 1% level using Dunnett’s test.

It is concluded that palladium di(4-oxopent-2-en-2-oate) did not induce mutation in five histidine-requiring strains (TA98, TA100, TA1535, TA1537 and TA102) of S. typhimurium when tested at concentrations up to 5000 μg/plate (the maximum recommended concentration according to current regulatory guidelines) or up to the limit of toxicity, in the absence and in the presence of S9.