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Toxicological information

Skin sensitisation

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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

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.

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