Dihydrogen hexahydroxyplatinate, compound with 2-aminoethanol (1:2)

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:

23 April - 25 June 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted according to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

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:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Dihydrogen hexahydroxyplatinate, compound with 2-aminoethanol (1:2)

EC Number:

268-717-3

EC Name:

Dihydrogen hexahydroxyplatinate, compound with 2-aminoethanol (1:2)

Cas Number:

68133-90-4

Molecular formula:

C2H7NO.1/2H6O6Pt.H

IUPAC Name:

dihydrogen hexahydroxyplatinate, compound with 2-aminoethanol (1:2)

Details on test material:

- Name of test material (as cited in study report): Dihydrogen hexachydroxyplatinate, compound with 2-aminoethanol (1:2) (CAS 68133-90-4)

- Substance type:
- Physical state: liquid
- Analytical purity:
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.: A-198-01
- Expiration date of the lot/batch:

- Stability under test conditions: not stated
- Storage condition of test material: Opaque plastic bottle; In desiccator at 4 deg C
- Other:

Method

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

Sprague-Dawley rat liver induced with phenobarbitone and betanaphthoflavone

Test concentrations with justification for top dose:

Two main experiments.
In the first, using the plate incorporation method, the test substance was assayed at 313, 625, 1250, 2500 or 5000 ug/plate in all five tester strains, in the absence or presence of S9. In the second, TA98, TA100, and WP2 uvrA strains were tested under the same experimental conditions as the first experiment, while for TA1535 and TA1537, a pre-incubation step was included.

Vehicle / solvent:

Sterile distilled water

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

Dimethoxysulphoxide (DMSO)

Negative solvent / vehicle controls:

yes

Remarks:

Untreated

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

Migrated to IUCLID6: in distilled water

Controls 2

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

Migrated to IUCLID6: in DMSO

Controls 3

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

Migrated to IUCLID6: in DMSO

Controls 4

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene in DMSO

Controls 5

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

Migrated to IUCLID6: in distilled water

Evaluation criteria:

For the test substance to be considered mutagenic, a two-fold (or more) increase in the mean revertant numbers must be observed at two-consecutive dose-levels or at the highest practiable dose-level only. In addition, there must be evidence of a dose-reponse relationship.

Statistics:

Regression analysis by the least squares method

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium, other: TA98, TA100

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

In main experiment one, two-fold, dose-related increases in revertant colonies compared to controls were seen in TA98, TA100, and WP2 uvrA strains, with and without S9.
In main experiment two, the test substance induced reproducible, dose-related, two-fold increases in the number of revertant colonies compared to controls in TA98, TA100, and WP2 uvrA strains, with and without S9. Two-fold increases in TA1537 were also seen using the pre-incubation method, at non-toxic dose-levels, with and without S9.

Applicant's summary and conclusion

Conclusions:

In an OECD Test Guideline 471 study, to GLP, dihydrogen hexachloroplatinate, compound with 2-aminoethanol (1:2) induced reverse mutations in strains of Salmonella typhimurium and Escherichia coli both with and without metabolic activation.

Executive summary:

In an OECD Test Guideline 471 study, conducted according to GLP, dihydrogen hexachloroplatinate, compound with 2-aminoethanol (1:2) was assessed for its ability to induce gene mutations in strains of S. typhimurium (TA1535, TA1537, TA98, TA100) and E. coli (WP2 uvrA). The test was performed in two independent experiments (involving the plate incorporation method, including a pre-incubation step for TA1535 and TA1537 in Experiment 2), with dose levels of up to 5000 μg/plate (determined following an initial toxicity test), both in the absence and presence of rat liver metabolic activation (S9).

In experiment 1, dose-related increases in revertant numbers, which were at least two-fold the control values, were observed in WP2 uvrA both with and without S9. The test item induced reproducible, large and dose-related increases in the number of revertant colonies, which were more than two-fold the control values, with TA98, TA100 and WP2 uvrA tester strains in the plate incorporation assays, at the higher dose levels both in the presence and absence of S9 metabolism. Increases in revertant numbers were also observed with TA1537 in the pre-incubation assay. These increases were greater than twice the control value at non-toxic dose-levels, both in the presence and absence of S9 metabolism.

It was concluded that dihydrogen hexachloroplatinate, compound with 2-aminoethanol (1:2) was mutagenic in S. typhimurium and E.coli under the reported experimental conditions.