Tetraammineplatinum (II) diacetate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 September - 1 November 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP, with slight deviations from the recommended temperature and humidity range

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

deviation of the temperature and humidity range

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

deviation of the temperature and humidity range

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

not specified

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, JMAFF (2000), including the most recent partial revisions

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Platinum (2+) tetraammine (SP-4-1) diacetate

IUPAC Name:

Platinum (2+) tetraammine (SP-4-1) diacetate

Constituent 2

Reference substance name:

127733-97-5

Cas Number:

127733-97-5

IUPAC Name:

127733-97-5

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Platinum (2+) tetraammine (SP-4-1) diacetate
- Substance type: No data
- Physical state: white crystalline powder
- Analytical purity: 95.2%
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: Pt (48.75%), Cl (0.029%)
- Isomers composition: Not applicable
- Purity test date: No data
- Lot/batch No.: GB 379
- Expiration date of the lot/batch: 28 June 2005
- Stability under test conditions: stable under storage conditions
- Storage condition of test material: room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 7-9 weeks
- Weight at study initiation: 1.30-1.57 kg
- Housing: individually in cages with perforated floors
- Diet (e.g. ad libitum): 100g/day of standard laboratory rabbit diet
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days before treatment initiation

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16.7-22.4 (specified range is 20 ± 3 deg C, a deviation at the lower end of the recommended temperature range of only 0.3 deg C is not expected to have affected the validity of the results)
- Humidity (%): 33-74 (recommended range is 30-70%, this deviation at the upper end of the recommended range of only 4% is not expected to affect the validity of the results)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 27 September 2004 To: 1 November 2004

Test system

Vehicle:

not specified

Controls:

other: the other eye of each animal remained untreated and served as the reference control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 92.7 mg
- Concentration (if solution): Not applicable

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): No data
- Purity: No data

Duration of treatment / exposure:

14 days

Observation period (in vivo):

Observed at 1, 24, 48 and 72 hr, and 7 and 14 days after instillation.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated eye not rinsed
- Time after start of exposure: not applicable

SCORING SYSTEM: The irritation was assessed according to the Draize classification system based on the extent of effects seen on the cornea, iris and conjunctiva in each animal.

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: corneal opacity

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Remarks on result:

other: reversibility not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

2

Remarks on result:

other: reversibility not applicable

Results 3

Irritation parameter:

other: conjunctivae redness score

Basis:

mean

Time point:

other: 24-72 hours

Score:

2.2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24-72 hours

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Irritation of the eye was limited to the conjunctivae and consisted of redness, chemosis and discharge (highest scores observed in an individual rabbit were 3, 2, 2 respectively). The irritation had completely resolved within 14 days.

Other effects:

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Animal	Mean 24 -72 hours
	Corneal opacity	Iris	Conjunctivae
			Redness	Chemosis
1	0.0	0.0	2.0	1.3
2	0.0	0.0	2.3	1.0
3	0.0	0.0	2.3	1.0
Mean	0.0	0.0	2.2	1.1

Table 1: Mean value eye irritation scores

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In an OECD guideline study, to GLP, platinum (2 +) tetraammine (SP-4 -1) diacetate produced conjunctival effects following instillation of the test material (93 mg) to the eyes of three male rabbits. The irritation had completely resolved within 14 days.

Executive summary:

In an OECD guideline study (TG 405), conducted according to GLP, approximately 93 mg of platinum (2 +) tetraammine (SP-4 -1) diacetate was instilled into one eye of each of three male New Zealand white rabbits. The other eye remained untreated and was used for control purposes.

Irritation of the conjunctivae, consisting of redness, chemosis and discharge (highest scores observed in an individual rabbit were 3, 2, 2 respectively) was observed in all three animals. The irritation had completely resolved within 14 days. No effects were seen on the iris or cornea. No corrosive effects were noted and there was no evidence of systemic toxicity. As the conjunctival redness score (calculated as mean of the scores at 24, 48 and 72 hr) was greater than or equal to 2 in all three animals, the test material met the criteria for classification as irritant category 2 according to EU CLP regulations.