Registration Dossier

Administrative data

Description of key information

In a US guideline study, moderate irritation was observed following a single 24-hr semi-occluded application of tetraammineplatinum dichloride to the intact or abraded skin of three rabbits (Nicholas and Jones, 1977a).

 

In a US guideline study, instillation of tetraammineplatinum dichloride (0.1 g) to the right eye of eight rabbits for 5 min or 24 hr caused irritation which was fully reversible within 7 days (Nicholas and Jones, 1977b).

 

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:
3 days; no data on dates (Report date January 1977)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not according to modern guidelines. No control sites; test material not washed off after the 24 hr exposure period.
Qualifier:
according to
Guideline:
other: US Federal register Vol. 38, No. 187, section 1500:41 (1973)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:

TEST ANIMALS
- Source: “recognised breeders”
- Age at study initiation: 12-14 weeks
- Weight at study initiation: about 2.2 kg
- Housing: Individually housed; type of cage not specified
- Diet (e.g. ad libitum): conventional diet, ad libitum
- Water (e.g. ad libitum): filtered water, ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-19
- Humidity (%): 50-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): natural lighting

IN-LIFE DATES: From: To:
Type of coverage:
semiocclusive
Preparation of test site:
other: shaved & abraded
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg (no data if applied as the powder or made into a paste

Duration of treatment / exposure:
24 hr
Observation period:
24 and 72 hr
Number of animals:
Six females
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm each of shaved dorsal skin and shaved and abraded dorsal skin
- % coverage: no data
- Type of wrap if used: applied on gauze held in place with “Sleek” adhesive tape. Entire trunk covered with an elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data; presumably substance not removed
- Time after start of exposure:

SCORING SYSTEM: assessed for primary irritation index at 24 and 72 hr. Scores for erythema/eschar formation and edema for both intact and abraded skin at both time points were totalled and divided by 24 to give the primary irritation index.
Primary irritation index Classification
0 non-irritant
> 0-2 mild irritant
> 2-5 moderate irritant
> 5-8 severe irritant

Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: Mean of 24- and 72-hr time points
Score:
2.8
Max. score:
8
Reversibility:
other: not assessed; animals only kept for 48 hrs after removal of the patch.
Remarks on result:
other: Score is the mean for intact and abraded skin
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Mean of 24- and 72-hr time points
Score:
5
Max. score:
16
Reversibility:
other: not assessed; animals only kept for 48 hrs after removal of the patch.
Remarks on result:
other: Score is the mean for intact and abraded skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Mean of 24- and 72-hr time points
Score:
6.2
Max. score:
16
Reversibility:
other: not assessed; animals only kept for 48 hrs after removal of the patch.
Remarks on result:
other: Score is the mean for intact and abraded skin
Other effects:
No indication that systemic effects were assessed.

Table 1: Individual rabbit results

 Rabbit No.  Time/hr  Erythema    Oedema  
     Abraded skin  Intact skin  Abraded skin  Intact skin
 1  24  1  1  2  2
   72  1  1  1  1
 2  24  1  1  1  1
   72  1  1  1  1
 3  24  2  2  2  2
   72  2  2  2  2
 4  24  1  1  2  2
   72  1  1  1  1
 5  24  1  1  3  1
   72  1  1  1  0
 6  24  1  1  2  2
   72  2  2  2  2
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
In a US guideline study, moderate irritation was observed following a single 24-hr semi-occluded application of tetraammine platinous chloride to the intact or abraded skin of three rabbits.
Executive summary:

In a US guideline study, the irritant potential of tetraammine platinous chloride was assessed on the intact and abraded skin of six female New Zealand white rabbits.

 

The test substance (0.5 g) was applied for 24-hr under semi-occlusion and assessed immediately upon removal of the patch as well as 48 hr later. Residual test material was not washed off the skin during this period. Moderate irritation was observed at both time points. Similar scores for both erythema/eschar formation and edema were reported for intact and abraded skin. The primary irritation index was calculated to be 2.8.

 

Mean erythema/eschar and oedema scores were below 2.3 for all six animals. However, the effects were only observed to be reversible in one animal within the 48-hr observation period.

 

Based on the results of this study, tetraammine platinous chloride should be classified as a skin irritant (category 2) according to EU CLP criteria (EC 1272/2008).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
No data (Report date March 1977)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not carried out to modern guidelines; not according to GLP
Qualifier:
according to
Guideline:
other: US Federal Register 37, No. 83, 28 April 1972, 191. 12
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: “recognised breeder”
- Age at study initiation: 12-14 weeks
- Weight at study initiation: mean 1.9 kg
- Housing: caged singly; no further data
- Diet (e.g. ad libitum): conventional diet; ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 ± 2
- Humidity (%): 50-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): natural lighting

IN-LIFE DATES: From: To:

Vehicle:
unchanged (no vehicle)
Controls:
other: yes, concurrent no treatment to left eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg into the right eye

VEHICLE
none
Duration of treatment / exposure:
Group 1: 5 min (5 animals); Group 2: 24 hr (3 animals)
Observation period (in vivo):
1, 24, 48, and 72 hr, then daily for a further 4 days
Number of animals or in vitro replicates:
8 females (5 with 5 min exposure (Group 1); 3 with 24 hr exposure (Group 2))
Irritation parameter:
overall irritation score
Remarks:
Group 1 - eyes rinsed after 5 mins
Basis:
mean
Remarks:
5 animals
Time point:
other: 1, 24, 48, 72 hours & 7 days
Score:
13.2
Max. score:
65
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4/5 gave positive response at 24 hours
Irritation parameter:
cornea opacity score
Remarks:
Group 1 - eyes rinsed after 5 mins
Basis:
mean
Remarks:
5 animals
Time point:
other: 1, 24, 48, 72 hours & 7 days
Score:
0
Max. score:
20
Irritation parameter:
iris score
Remarks:
Group 1 - eyes rinsed after 5 mins
Basis:
mean
Remarks:
5 animals
Time point:
other: 1, 24, 48, 72 hours & 7 days
Score:
0
Max. score:
10
Irritation parameter:
conjunctivae score
Remarks:
(Redness) Group 1 - eyes rinsed after 5 mins
Basis:
mean
Remarks:
5 animals
Time point:
other: 1, 24, 48, 72 hours & 7 days
Score:
7.2
Max. score:
15
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Remarks:
Group 1 - eyes rinsed after 5 mins
Basis:
mean
Remarks:
5 animals
Time point:
other: 1, 24, 48, 72 hours & 7 days
Score:
5.8
Max. score:
20
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Remarks:
Group 2 - eyes rinsed after 24 hours
Basis:
mean
Remarks:
3 animals
Time point:
other: 1, 24, 48, 72 hours & 7 days
Score:
13.7
Max. score:
65
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 3/3 gave positive response at 24 hours
Irritation parameter:
cornea opacity score
Remarks:
Group 2 - eyes rinsed after 24 hours
Basis:
mean
Remarks:
3 animals
Time point:
other: 1, 24, 48, 72 hours & 7 days
Score:
0
Max. score:
20
Irritation parameter:
iris score
Remarks:
Group 2 - eyes rinsed after 24 hours
Basis:
mean
Remarks:
3 animals
Time point:
other: 1, 24, 48, 72 hours & 7 days
Score:
0
Max. score:
10
Irritation parameter:
conjunctivae score
Remarks:
(Redness) Group 2 - eyes rinsed after 24 hours
Basis:
mean
Remarks:
3 animals
Time point:
other: 1, 24, 48, 72 hours & 7 days
Score:
7
Max. score:
15
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Remarks:
Group 2 - eyes rinsed after 24 hours
Basis:
mean
Remarks:
3 animals
Time point:
other: 1, 24, 48, 72 hours & 7 days
Score:
6.7
Max. score:
20
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Group 1 Rabbits (eyes rinsed after 5 mins): Four out of five animals gave a positive response at the 24 hour observation. the reaction reduced and no positive reaction was apparent at 7 days.

Group 2 Rabbits (eyes rinsed after 24 hours): All three animals gave a positive response at the 24 hour observation. The reactions reduced and all eyes were clear at 7 days.
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
In a US guideline study, instillation of tetraammine platinous chloride (0.1 g) to the right eye of eight rabbits for 5 min or 24 hr caused irritation which was fully reversible within 7 days.
Executive summary:

In a US guideline study, the eye irritant potential of tetraammine platinous chloride was assessed in eight female New Zealand white rabbits. A group of three rabbits received a 0.1 g instillation of the powdered test material to the right eye. After 24 hr the eyes were rinsed and the animals were observed for up to 7 days. Another group of five rabbits were subject to the same procedure though the eye was rinsed after 5 minutes.

Redness and swelling of the conjunctiva occurred within 1 hr of exposure in both groups, and was fully reversible within 7 days. No effects were evident in the iris or cornea within the observation period. No differences in the severity of the conjunctival effects were apparent for the two exposure times.

Based on the results of this study, the test material should be classified as an eye irritant (category 2) under EU CLP criteria (EC 1272/2008).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No relevant irritation/corrosion human 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 a US guideline study, the irritant potential of tetraammine platinous chloride was assessed on the intact and abraded skin of six female New Zealand white rabbits. The test substance (0.5 g) was applied for 24-hr under semi-occlusion and assessed for signs of erythema/eschar formation and edema immediately upon removal of the patch as well as 48 hr later. Residual test material was not washed off the skin during this period. Moderate irritation was observed at both time points. Similar scores for both erythema/eschar formation and edema were reported for intact and abraded skin. The primary irritation index was calculated to be 2.8 (mean for intact and abraded skin) (Nicholas and Jones, 1977a). As the test sites were only assessed 48 hr after patch removal, it was not possible to calculate mean erythema/eschar and oedema scores for the six animalsand to give a definitive classification interpretation according to EU CLP criteria (EC 1272/2008). However, the moderate irritant effects were only observed to be reversible in one animal within the observation period.Hence, it is considered precautionary to classify the test material as a skin irritant (Category 2).

 

In a US guideline study, the eye irritant potential of tetraammine platinous chloride was assessed in eight female New Zealand white rabbits. A group of three rabbits received a 0.1 g instillation of the powdered test material to the right eye. After 24 hr the eyes were rinsed and the animals were observed for up to 7 days. Another group of five rabbits were subject to the same procedure though the eye was rinsed after 5 minutes. Redness and swelling of the conjunctiva occurred within 1 hr of exposure in both groups, and was fully reversible within 7 days. No effects were evident in the iris or cornea within the observation period. No differences in the severity of the conjunctival effects were apparent for the two exposure times (Nicholas and Jones, 1977b). Based on the results of this study, the test material should be classified as an eye irritant (category 2) under EU CLP criteria (EC 1272/2008).

 

No respiratory tract irritation data were identified.

Justification for classification or non-classification

Based on the results of the available skin and eye irritation studies (in rabbits), tetraammineplatinum dichloride should be classified as a skin irritant (category 2) and for eye irritation (category 2), according to EU CLP criteria (EC 1272/2008).