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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).