Diammineplatinum(II) nitrite

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 April – 24 August 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye 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: no data
- 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 / tissue source

Species:

rabbit

Strain:

other: White Russian (albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Origin/breeder: ASTA Pharma AG, D-4800 Bielefeld 14
- Age at study initiation: 8-11 months
- Weight at study initiation: 2.78-2.98 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): 20.5-23
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12 hrs natural light-dark-rhythm (6 pm to 6 am) / 12 hrs artificial lighting

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye of each of the three rabbits was used as the control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of test material applied to the conjuctival sac of the left eye

Duration of treatment / exposure:

Both lids were briefly closed by gentle finger pressure

Observation period (in vivo):

Inspection of the eyes occurred 1, 24, 48 and 72 hrs after application and then daily until day 21. An additional examination was performed on day 124.

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was not rinsed

SCORING SYSTEM: Signs of irritation on the cornea, iris and conjunctiva were assessed quantitatively and qualitatively using the Draize scale (see attachment 5 for details) assessed at 1, 24, 48, and 72 hrs following application of the test material into the eye. The irritation index is given by the sum of these scores, following a modified method according to Gilman et al. 1983:
Index ranges Gradation
0-10 non-irritant
11-25 slightly irritant
26-56 moderately irritant
57-110 severely irritant

TOOL USED TO ASSESS SCORE: Cliptrix pencil light

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

other: irritation index is the sum of the scores from the cornea, iris and conjuctiva

Time point:

other: 72 hrs

Score:

39

Reversibility:

not fully reversible within: 3 months after application

Other effects:

There were no systemic toxic effects observed.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In a guideline study, to GLP, instillation of dinitrodiammine-platinum(II) into the conjuctival sac of the left eye of three rabbits caused moderate irritation according to the Draize scale. However, the test substance caused severe and sometimes irreversible effects, especially on the cornea, and therefore should be classified as Category 1 (irreversible effects on the eye) under EU CLP criteria.

Executive summary:

In an OECD Test Guideline 405 study, conducted according to GLP, dinitrodiammine-platinum(II) was investigated for irritant effects on the rabbit eye and associated mucous membranes following instillation of 0.1 g into the conjuctival sac of the left eye of each of three animals.

No systemic toxic effects were detected, and the untreated control eyes showed no changes. Following application of the test material, slight partial or moderate circumcorneal hyperaemia was seen in the iris. Regarding the conjuctival sac, diffuse crimson discolouration, white foci, single haemorrhages and eye lid swelling were observed, of which some were considered severe effects. The cornea was particularly affected, with changes including diffuse opacity or opaque areas and diffuse capacity or easily discernable translucent areas, obscured iris and vessel ingrowth. The cornea lesions persisted in two rabbits when examined 3 months after application of the test material. After the 72 hr observation period, the primary index irritation index was 39, indicating a moderate eye irritant. However, as the test substance caused severe and sometimes irreversible effects (notably) on the cornea, the study authors conclude that dinitrodiammine-platinum(II) should be classified as a severe eye irritant in this test system.

 

According to EU CLP criteria (EC 1272/2008), dinitrodiammine-platinum(II) should be classified as Category 1 (irreversible effects on the eye).