Hexachloroplatinic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 November 2002 - 14 March 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD guideline study, to GLP

Remarks:

The nature of the reactions in the test group are difficult to interpret

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study conducted in 2003

Test material

Test material information

Constituent 1

Reference substance name:

Hexachloroplatinic acid

EC Number:

241-010-7

EC Name:

Hexachloroplatinic acid

Cas Number:

16941-12-1

Molecular formula:

Cl6Pt.2H

IUPAC Name:

platinum(4+) dihydrogen hexachloride

Details on test material:

- Name of test material (as cited in study report): Dihydrogen hexachloroplatinate(IV)-solution

- Substance type:
- Physical state: liquid
- Analytical purity: 99.95%
- Impurities (identity and concentrations): not stated
- Composition of test material, percentage of components: 70.8 weight % (of H2[PtCl6] in the solution)

- Purity test date: not stated
- Lot/batch No.: 4513936306
- Expiration date of the lot/batch: 12 September 2003

- Stability under test conditions: at least 96 hr
- Storage condition of test material: at room temp in the dark
- Other:

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, germany
- Age at study initiation: young adult animals (approx 4 weeks old)
- Weight at study initiation: 328-329 g
- Housing: max 5 animals per cage, purified sawdust bedding
- Diet (e.g. ad libitum): standard guinea-pig diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/-3
- Humidity (%): 30-70
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

5%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

5%

No. of animals per dose:

Experimental group: 10 animals
Control group: 5 animals

Details on study design:

Induction
Day 1.
Experimental animals:
Three pairs of intradermal injections
(0.1 ml/site) were made to the clipped back (scapular region) of ten nulliparous non-pregnant female guinea-pigs with:
A) A 1:1 w/w mixture of Freunds’ Complete Adjuvant with water,
B) The test substance at a concentration of 0.02%,
C) A 1:1 w/w mixture of the test substance at 0.04% and Freunds’ Complete Adjuvant.
One of each pair was on either side of the midline and from cranial (A) to caudal (C).
Day 3.
The dermal reactions caused by the injections were assessed for irritation.
Day 8.
The scapular region between the injection sites was clipped and subsequently treated with 0.5 ml of a 5% test substance concentration under occlusion using a Metaline patch (2x3 cm) mounted on medical tape which was held in place with micropore tape and subsequently Coban elastic tape.
The dressing was removed after 48 hours,
the skin cleaned of residual test substance using water, and the dermal reactions were again assessed for signs of irritation.
Control animals:
The five control animals were treated as described for the experimental animals except that, instead of the test substance, vehicle (water) alone was administered. Water was selected as the vehicle for induction and challenge applications based on trial formulations performed at NOTOX.
Challenge
Day 22
Following a 14-day rest period, one flank of all animals was clipped and treated by epidermal application of a 5% test substance concentration and the vehicle (water) at 0.1 ml each, using Patch Test Plasters (Curatest®). The patches were held in place with Micropore tape and subsequently Coban elastic bandage.
The patch was removed after 24 hrs covered contact and the skin cleaned with water to remove any residual test substance or vehicle. The treated sites were assessed for sensitization reactions 24 and 48 hours after removal of the dressing.
Skin reactions were graded according
to the following numerical scoring systems.
Furthermore, a description of all other
(local) effects was recorded. All skin reactions will be considered signs of sensitisation provided that such reactions are less severe or are less persistent in the control group.
Grading Challenge Reactions:
No visible change.........................................0
Discrete or patchy erythema......................1
Moderate and confluent erythema............2
Moderate erythema and swelling...............3
Intense erythema and swelling...................4

Challenge controls:

Yes - vehicle (water - Milli-U)

Positive control substance(s):

yes

Remarks:

alpha - hexylcinnamicaldehyde tech. 85%

Results and discussion

Positive control results:

Sensitization rate of 50% (5/10 animals) to a 20% solution of positive control in a reliability check conducted October/November 2002. From these results the investigators conclude that these animals are an appropriate model.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5%

No. with + reactions:

9

Total no. in group:

10

Clinical observations:

scaliness

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 9.0. Total no. in groups: 10.0. Clinical observations: scaliness.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

0

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 0.0.

Any other information on results incl. tables

Yellow staining was observed at the test substance treated skin sites, 24 and 48 hours after challenge. This staining did not hamper the scoring of the skin reactions.

No reactions were seen with the vehicle challenge controls in both (5) control and (10) test animals.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Dihydrogen hexachloroplatinate(IV) solution was sensitising to the skin of guinea-pigs.

Executive summary:

In a guideline study conducted to GLP, the sensitization potential of dihydrogen hexachloroplatinate(IV) solution was assessed using the guinea-pig maximisation test. Groups of 10 animals were induced by intradermal injection with a 0.02% concentration followed by epidermal exposure to a 5% concentration. Five control animals were similarly treated, but with vehicle (water) alone. Two weeks following the epidermal application, all animals were challenged with a 5% test substance concentration or vehicle.

Skin reactions of grade 1 were observed in three test animals and scaliness was observed in nine test animals in response to the 5% test substance concentration challenege. No skin reactions were evident in the control aniamls. These skin reactions were considered indicative of sensitization. These results indicate a sensitization rate of 90%. However, the nature of the reactions in the test group are difficult to interpret since erythema was not seen in all responding animals, rather there was the presence of dermal scaliness, which was not seen in control animals.