Tetraammineplatinum (II) diacetate

Endpoint summary

Description of key information

In a guideline study (OECD TG 404), tetraammineplatinum(II) diacetate was not irritating to the clipped skin of three rabbits following a 4 hr semi-occlusive application (Beerens-Heijnen, 2004a).

 

In a guideline study (OECD TG 405), to GLP, tetraammineplatinum(II) 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 (Beerens-Heijnen, 2004b).

 

No relevant respiratory tract irritation data were identified.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 September - 15 October 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: 7-9 weeks
- Weight at study initiation: 1.43-1.67 kg
- Housing: individual cages with perforated floors
- Diet (e.g. ad libitum): 100g/day (standard laboratory rabbit diet)
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: at least 5 days before treatment initiation

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.2-22.3 deg C
- Humidity (%): 33-70% humidity
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hr light/12 hr dark

IN-LIFE DATES: From: 21 September 2004 To: 15 October 2004

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

not specified

Remarks:

0.3 mL used to moisten the test material

Controls:

other: adjacent areas of the untreated skin of each animal served as controls

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): Not applicable

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.3 mL
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): No data
- Purity: No data

Duration of treatment / exposure:

4 hours

Observation period:

Animals observed at 1, 24, 48 and 72 hr after removal of the test material

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm squared
- % coverage: No data
- Type of wrap if used: Micropore tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin cleared of residual test material using water
- Time after start of exposure: 4 hours

SCORING SYSTEM: The irritation was assessed according to the Draize classification system based on the extent of formation of erythema, eschar and oedema in each test subject.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

8

Remarks on result:

other: Reversibility not applicable

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Remarks on result:

other: Reversibility not applicable

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

4

Remarks on result:

other: Reversibility not applicable

Irritant / corrosive response data:

No irritant or corrosive effect was observed on the skin after 4 hour exposure to the test material

Other effects:

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

Animal	Mean 24 -72 hours
	Erythema	Oedema
220	0	0
262	0	0
264	0	0
Mean	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

In a guideline study, to GLP, platinum (2+) tetraammine (SP-4 -1) diacetate was not irritating to the clipped skin of three New Zealand white rabbits following a 4 hr semi-occlusive application.

Executive summary:

In an OECD Test Guideline 404 study, to GLP, 0.5 g of platinum (2+) tetraammine (SP-4 -1) diacetate was applied to the clipped skin of 3 male New Zealand white rabbits. After 4 hours, the semi-occlusive dressings were removed and the skin sites assessed for signs of irritation (oedema and erythema/eschar) at 1, 24, 48 and 72 hours.

 

No erythema/eschar or oedema was seen at any of the observation points. The test material produced a primary irritation index of 0 and was classified as non-irritant to rabbit skin according to the Draize classification system. No corrosive effects were noted and there was no evidence of systemic toxicity. The test material did not meet the criteria for classification as irritant or corrosive according to EU CLP regulations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

deviation of the temperature and humidity range

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

deviation of the temperature and humidity range

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

not specified

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

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

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

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

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

2

Remarks on result:

other: reversibility not applicable

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No relevant human irritation/corrosion data were identified. No in vitro skin or eye irritation studies were identified, or are required, as reliable in vivo studies are already available.

 

In an OECD Test Guideline 404 study, to GLP, 0.5 g of platinum (2+) tetraammine (SP-4 -1) diacetate was applied to the clipped skin of 3 male New Zealand white rabbits. After 4 hours, the semi-occlusive dressings were removed and the skin sites assessed for signs of irritation (oedema and erythema/eschar) at 1, 24, 48 and 72 hours. No erythema/eschar or oedema was seen at any of the observation points. The test material produced a primary irritation index of 0 and was classified as non-irritant to rabbit skin according to the Draize classification system. No corrosive effects were noted and there was no evidence of systemic toxicity (Beerens-Heijnen, 2004a).

 

In an OECD guideline study (TG 405), conducted according to GLP, approximately 93 mg of tetraammineplatinum(II) 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 (Beerens-Heijnen, 2004b).

 

No respiratory tract irritation data were identified. A new study was not conducted as it is not a REACH Standard Information Requirement.

Justification for classification or non-classification

Based on the results of the available skin and eye irritation studies (in rabbits), tetraammineplatinum(II) diacetate does not require classification as a skin irritant but should be classified for eye irritation (category 2), according to EU CLP criteria (EC 1272/2008).