tetraammine platinum (II) hydrogen carbonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 June 1997 - 7 July 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP, with a slight deviation from the recommended humidity range

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

relative humidity was above the recommended range stated in the guideline

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

relative humidity was above the recommended range stated in the guideline

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetramine platinum hydrogencarbonate

IUPAC Name:

Tetramine platinum hydrogencarbonate

Constituent 2

Reference substance name:

123439-82-7

Cas Number:

123439-82-7

IUPAC Name:

123439-82-7

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Tetramine platinum hydrogencarbonate
- Substance type: No data
- Physical state: white powder
- Analytical purity: >99.9%
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: Tetramine platinum hydrogen carbonate (>99.9%)
- Isomers composition: Not applicable
- Purity test date: No data
- Lot/batch No.: 02/95
- Expiration date of the lot/batch: 31/12/1999
- Stability under test conditions: stable throughout the experimental period
- Storage condition of test material: closed container at room temperature
- Other: pH was about 8 (concentrated solution)

Test animals / tissue source

Species:

rabbit

Strain:

other: White russian (albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ASTA Medica AG, D-33790 Halle/Westfalen
- Age at study initiation: 39-41 months
- Weight at study initiation: 2.07-2.96 kg
- Housing: stainless steel cages with grating floor, one animal per cage
- Diet (e.g. ad libitum): 120 g/animal each day (sniff K-Z, complete diet for rabbits-breeding)
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: at least one day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-20.5 deg C
- Humidity (%): 53-84% (recommended humidity range is 30-70%. The peak may have occurred during room cleaning i.e. only for a short period of time. It is therefore considered not to compromise the validity of the results.)
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 9 June 1997 To: 7 July 1997

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye acted as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 90.1, 106.9 or 107.1 mg (representing a volume of about 0.1 mL)
- Concentration (if solution): Not applicable

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

Duration of treatment / exposure:

21 days

Observation period (in vivo):

Observed at 1, 24, 48 and 72 hrs, then daily until day 21.

Number of animals or in vitro replicates:

3 males

Details on study design:

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

SCORING SYSTEM: DRAIZE scale

TOOL USED TO ASSESS SCORE: Cliptrix pencil light

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1-72 hours

Score:

20

Max. score:

110

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: In one animal only were the findings not reversible within 21 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1-72 hours

Score:

6.7

Max. score:

80

Reversibility:

not fully reversible within: 21 days

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1-72 hours

Score:

2.1

Max. score:

10

Reversibility:

fully reversible within: 11 days

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1-72 hours

Score:

11.2

Max. score:

20

Reversibility:

not fully reversible within: 21 days

Results 5

Irritation parameter:

other: corneal opacity

Basis:

mean

Time point:

other: 1-72 hours

Score:

0.3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 6

Irritation parameter:

other: iris evaluation

Basis:

mean

Time point:

other: 1-72 hours

Score:

0.4

Max. score:

2

Reversibility:

fully reversible within: 11 days

Results 7

Irritation parameter:

other: conjunctival redness score

Basis:

mean

Time point:

other: 1-72 hours

Score:

1.7

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Results 8

Irritation parameter:

other: conjunctival chemosis score

Basis:

mean

Time point:

other: 1-72 hours

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritant / corrosive response data:

Diffuse corneal opacity was observed in two animals 48 hours after application, in one animal this disappeared after 6 days while the other showed translucent opacity by day 10. The corneal area involved was greater than three quarters in both animals. The cornea of the third animal was unremarkable. Slight to moderate circumcorneal hyperemia was apparent in two animals, lasting from 2 to 6 days or 1 to 10 days after application respectively. The iris of the third animal was unremarkable. The conjunctivae of all three animals were hyperemic immediately after application. In one animal the findings had completely disappeared by day 7, while the other two animals showed worsening up until 3 or 4 days after application with the former showing reversibility by day 9 while the latter persisted the entire 21-day observation period. Swelling (including nicitating membranes) occurred in all three animals, and persisted in one animal until day 21.

Other effects:

The general condition of the animals was undisturbed. Conjunctival discharge was observed in all three animals at 1 hr and lasted until days 6, 8 and 21 (still present at the end of the observation period) respectively. Signs of irritancy aggravated during the course of the study and one animal showed an irreversible effect in the course of the 21 day observation period. Nevertheless, according to the study report "the development of the findings towards the end of the study indicates a tendency to reversibility" and thus do not justify a diagnosis of "severe eye lesions".

Any other information on results incl. tables

Table 1: Mean eye irritation scores for each animal

Animal	Mean 1-72 hours
	Corneal opacity	Iris	Conjunctivae
			Redness	Chemosis
1	0.7	0.7	2.0	1.7
2	0.0	0.0	1.7	0.7
3	0.7	1.0	1.7	2.7
Mean	0.3	0.4	1.7	1.3

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

In a guideline study (OECD TG 405), to GLP, tetraammineplatinum(II) hydrogencarbonate produced slight irritation following instillation of the test material (0.1 mL) to the eyes of three rabbits. Effects in one animal persisted until the end of the observation period, though the development of these findings indicated a tendency to reversibility.

Executive summary:

In an OECD guideline study (TG 405), conducted according to GLP, tetraammineplatinum(II) hydrogencarbonate (90.1, 106.9 or 107.1 mg, representing a volume of about 0.1 mL) was instilled into one eye of each of three male white Russian rabbits. The other eye remained untreated and was used for control purposes.

 

Corneal irritation was observed in two out of the three animals after 2 days. Within 6 days the effects in one animal were resolved while the effects in the other animal were still present at the end of the 21-day observation period. Iris irritation was also observed in two out of the three animals, with effects lasting until days 6 and 10 respectively. Conjunctival irritation, consisting of redness, chemosis and discharge, was observed in all three animals. In two animals, this had completely resolved within 6 and 8 days respectively while the effects in the other animal persisted until the end of the observation period. The test material produced an overall eye irritation index score of 20.0 [maximum total score possible = 110] (mean of the scores 1 -72 hr) and was classified as slightly irritant to the rabbit eye according to a modified Draize classification system. The general condition of the animals was not adversely affected. In spite of the persistent effects observed in one animal, the development of these findings towards the end of the observation period indicated a tendency to reversibility.

 

Nevertheless, based on the persistent effects observed in one animal in this study, the test material should be classified for serious eye damage (category 1) according to EU CLP criteria (EC 1272/2008).