Diammineplatinum(II) nitrite

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 to 7 April 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diammineplatinum(II) nitrite

EC Number:

238-203-3

EC Name:

Diammineplatinum(II) nitrite

Cas Number:

14286-02-3

Molecular formula:

H6N4O4Pt

IUPAC Name:

diiminodinitroplatinumbis(ylium)

Details on test material:

- Name of test material (as cited in study report): Dinitrodiammine-platinum(II)
- Substance type: yellow powder
- Physical state: solid
- Analytical purity: 60% platinum
- Lot/batch No.: 6734
- Stability under test conditions: not indicated by the sponsor
- Storage condition of test material: kept refrigerated with a drying agent

Test animals

Species:

rabbit

Strain:

other: White Russian (albino)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder: ASTA Pharma AG, D-4800 Bielefeld 14
- Age at study initiation: Male 10 months, females 11 and 12 months
- Weight at study initiation: Male 2.75 kg, females 2.58 and 3.02 kg
- Housing: Stainless steel cages with grating floor, one animal/cage
- Diet (e.g. ad libitum): Approx. 120 g/day standard diet
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: One day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5-23.5
- Humidity (%): 45-60
- Photoperiod (hrs dark / hrs light): 12 hrs natural light-dark-rhythm (6 pm to 6 am)/ 12 hrs artificial lighting

Test system

Type of coverage:

occlusive

Preparation of test site:

other: clipped free of hair one day before treatment

Vehicle:

water

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Concentration (if solution): about 3 g/ml (moistened with 0.17 mL demineralised water)

Duration of treatment / exposure:

4 hours

Observation period:

Inspection of the skin occurred 1, 24, 48 and 72 hrs after removal of the patches

Number of animals:

Three (one male and two females)

Details on study design:

TEST SITE
- Area of exposure: The site of application was covered with a linen cloth (approx. 6.25 cm2) which adhered to a synthetic film glue
- Type of wrap if used: A bandage (Acrylastic No. 2408, width 8 cm) wrapped several times around the trunk provided complete occlusion

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After removal of the patch, remaining test material “was gently washed off as far as possible”
- Time after start of exposure: about 4 hours

SCORING SYSTEM: The treated skin area was qualitatively and quantitatively assessed using the Draize method at 1, 24, 48, and 72 hrs following removal of the patches. The irritation index is given by the sum of the mean values for erythema (and eschar) formation, and edema, following a modified method according to Gilman et al. 1983:
Index ranges Gradation
0-0.5 non-irritant
0.6-3 slightly irritant
3.1-5 moderately irritant
5.1-8 severely irritant
In addition, attention was paid to the occurrence of further reactions on the skin (including corrosive effects) and to clinical symptoms (systemic toxic effects).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1, 24, 48, and 72 hrs

Score:

0

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48, and 72 hrs

Score:

0

Results 3

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 1, 24, 48, and 72 hrs

Score:

0

Irritant / corrosive response data:

No erythema or edema (Draize score of 0) was seen on the skin of the animals within the 3 day observation period.

Other effects:

Systemic toxic effects did not occur and the general condition of the rabbits was not affected by treatment.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a guideline study, to GLP, no irritation potential was observed when 0.5 g dinitrodiammine-platinum(II) was applied (under occlusion for 4 hr) to the clipped, intact skin of three rabbits.

Executive summary:

In an OECD Test Guideline 404 study, conducted according to GLP, dinitrodiammine-platinum(II) (0.5 g, moistened with 0.17 mL water) was applied (occluded) to the clipped intact skin of 3 White Russian rabbits. After 4 hours, the dressings were removed and the treated skin sites were washed and subsequently observed for erythema and oedema at 1, 24, 48 and 72 hours.

 

No skin reactions were recorded at any time point in any animal during the 72 -hr observation period. The primary dermal irritation index was therefore 0, and dinitrodiammine-platinum(II) was classified as a non-irritant to rabbit skin under the conditions of the test. Systemic toxic effects were not detected and the general condition of the rabbits was unaffected by treatment.

 

No skin classification, according to EU CLP criteria (EC 1272/2008), is required on the basis of this study.