Dipotassium tetrachloroplatinate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reasonable-quality study (on read-across surrogate), not performed to OECD guideline, but it appears to have been well-conducted, matches the guideline in some important respects, and has been adequately reported.

Data source

Reference

Reference Type:

publication

Title:

Contact hypersensitivity to disodium hexachloroplatinate in mice

Author:

Schuppe H-C et al.

Year:

1997

Bibliographic source:

Toxicology Letters, 93 (2,3), 125-133

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

No mention of guideline in publication, but a similar methodology was employed

Deviations:

yes

Remarks:

Numerous - see "Any other information on materials and methods incl. tables", below

Principles of method if other than guideline:

Local lymph node (auricular lymph node; ALN) assay to detect primary immune response.

GLP compliance:

not specified

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Disodium hexachloroplatinate hexahydrate

IUPAC Name:

Disodium hexachloroplatinate hexahydrate

Constituent 2

Reference substance name:

Na2[PtCl6].6H2O

IUPAC Name:

Na2[PtCl6].6H2O

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Disodium hexachloroplatinate
- Molecular formula (if other than submission substance): Na2[PtCl6].6H2O
- Molecular weight (if other than submission substance): 561.9 g/mol
- Smiles notation (if other than submission substance): [Pt+4]([Cl-])([Cl-])([Cl-])([Cl-])([Cl-])[Cl-].[Na+].[Na+] (dehydrated form)
- InChl (if other than submission substance): 1S/6ClH.2Na.Pt/h6*1H;;;/q;;;;;;2*+1;+4/p-6 (dehydrated form)
- Structural formula attached as image file (if other than submission substance): see Fig. (dehydrated form)
- Substance type: Technical product
- Physical state: No data
- Analytical purity: No data
- Lot/batch No.: No data
- Stability under test conditions: No data
- Storage condition of test material: No data
- Other: supplied by Degussa AG (Hanau, Germany)

In vivo test system

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: University of Dusseldorf
- Age at study initiation: 6-8 weeks
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): standard diet (not further specified) ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

Study design: in vivo (LLNA)

Vehicle:

other: acetone

Concentration:

5%.
[Results for "lower concentrations" of the test compound were briefly cited in the publication, but no further details were given.]

No. of animals per dose:

5

Details on study design:

Topical treatment (25 ul) to the dorsum of both ears on 4 consecutive days. Lymph node cells analysed around 48-hours after the last exposure.

End-point: ALN index (cell count from treated group divided by cell count from vehicle control); global ALN cell count (the former is a more sensitive parameter, presumably for measuring immume/sensitisation response.

Controls were treated with vehicle alone [no further details given].

Experiment repeated in triplicate.

Positive control substance(s):

other: oxazolone, 1% in acetone, single application around 48 hours before ALN cell analysis

Statistics:

Results were analyzed for significance emplpying the U-test of Mann-Whitney.

Results and discussion

Positive control results:

The positive control caused a 16.5-fold increase in number of proliferating cells compared to the control.

In vivo (LLNA)

Results

Key result

Parameter:

other: ALN cell yield

Remarks:

x 1,000,000 cells

Value:

16.9

Variability:

Standard deviation +/- 3.7

Test group / Remarks:

Mean

Remarks on result:

other: 4-Fold increase in global ALN cell yield per animal compared to control (4.3 E6 cells).

Remarks:

p<0.01

Any other information on results incl. tables

Compared to controls, the test substance caused a 23-fold increase in number of auricular lymph node (ALN) proliferating cells (ALN index = 22.8), and there was a 4-fold increase in global ALN cell yield per animal (mean global ALN cell yield +/- SD, 16.9 +/- 3.7 vs 4.3 +/- 1.5 (x 1,000,000 cells), p<0.01). The response was said to be comparable to that obtained following a single dose of the potent skin sensitiser oxazolone.

At lower concentrations of test compound [not specified and no further details given], no such increase observed (ALN index <2); the vehicle elicited an ALN index of <1.5 (i.e. reported as no reactivity).

The proliferative response detected in the ALN following skin exposure to sodium hexachloroplatinate was said to provide suggestive evidence for the predominant activation of CD4+ T lymphocytes.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

In a study broadly comparable to the local lymph node assay in mice, disodium hexachloroplatinate induced a proliferation of auricular lymph node (ALN) cells consistent with a potential to cause skin sensitisation.

Executive summary:

In a study broadly comparable to the local lymph node assay (LLNA), groups of 5 mice were subjected to local applications, on both ears, of 5% disodium hexachloroplatinate on each of 4 consecutive days. Around 48 hours after the last exposure, the auricular lymph nodes cells were analysed.

The test substance caused a 23-fold increase in number of ALN (auricular lymph node) proliferating cells, and a 4 -fold increase in global ALN cell yield per animal compared to vehicle controls. This response was comparable to that seen in the positive control, indicating that disodium hexachlorplatinate has skin sensitisation potential.