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Description of key information

In a guideline study (OECD TG 404), to GLP, tetraammineplatinum(II) hydrogen carbonate was very slightly irritating to the clipped skin of one of three rabbits following a 4-hr occlusive application; no irritation potential was observed in the other two animals (Berthold, 1997b).

 

In a guideline study (OECD TG 405), to GLP, tetraammineplatinum(II) hydrogen carbonate 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 (Berthold, 1997c).

 

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:
27 May 1997 - 6 June 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP, minor deviation from the recommended humidity range and the use of an occlusive patch
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
relative humidity was above the range stated in the protocol on two occassions for approximately one hour each; guideline recommends the use of a semi-occlusive dressing
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
relative humidity was above the range stated in the protocol on two occassions for approximately one hour each; guideline recommends the use of a semi-occlusive dressing
GLP compliance:
yes
Species:
rabbit
Strain:
other: white russian (albino)
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: ASTA Medica AG, D-33790 Halle-Westfalen
- Age at study initiation: 20-35 months
- Weight at study initiation: 2.39-3.01 kg
- Housing: stainless steel cages with grating floor, one animal per cage
- Diet (e.g. ad libitum): 120 g/animal each day (ssniff 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 deg C
- Humidity (%): 40-80% (recommended humidity range is 30-70%, this slight deviation is not expected to affect the study findings)
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 27 May 1997 To: 6 June 1997
Type of coverage:
occlusive
Preparation of test site:
clipped
Vehicle:
other: test substance was moistened with water to ensure a tight contact with the skin
Controls:
other: the opposite area of dorsal skin was treated in the same way but without test substance
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): 0.14 mL demineralized water
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): No data
- Purity: No data
Duration of treatment / exposure:
4 hours
Observation period:
Observed at 1, 24, 48 and 72 hr (two animals) and daily until day 9 (one animal) after application
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6.25 cm squared
- % coverage: No data
- Type of wrap if used: Acrylastic bandage No. 2408, width 8 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Gentle washing as at the end of the exposition time
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize irritation index
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1-72 hours
Score:
0.3
Max. score:
8
Reversibility:
fully reversible within: 9 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1-72 hours
Score:
0.17
Max. score:
4
Reversibility:
fully reversible within: 9 days
Remarks on result:
other: includes eschar
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1-72 hours
Score:
0.08
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritant / corrosive response data:
Erythema and edema (both very slight) were observed in one animal, on day 2-8 and day 3-5, respectively. Eschar formation was also detected in the same animal on day 5, this started to peel on day 6 and had completely disappeared by day 9.
Other effects:
The general condition of the animals was not affected. Systemic toxic effects did not occur after dermal application of the test substance.
Interpretation of results:
GHS criteria not met
Conclusions:
In a guideline study (OECD TG 404), to GLP, tetraammineplatinum(II) hydrogen carbonate was very slightly irritating to the clipped skin of one of three rabbits following a 4-hr occlusive application; no irritation potential was observed in the other two animals.
Executive summary:

In an OECD Test Guideline 404 study, conducted according to GLP, a 4 hour, occlusive application of tetraammineplatinum(II) hydrogencarbonate (0.5 g moistened with 0.14 mL water) was made to the clipped skin of three male white Russian rabbits. After 4 hours, the dressings were removed and the skin sites assessed for signs of irritation (edema and erythema/eschar) at 1, 24, 48 and 72 hours.

 

Erythema (including eschar) and edema (both very slight) were observed in one of the three animals after 48 and 72 hr respectively. Effects were reversible within 9 days of application. No signs of irritation were apparent in the other two animals. The test material produced a primary dermal irritation index of 0.3 [maximum total score = 8.0] (mean of scores at 1 -72 hr after application)and was classified as non-irritant to rabbit skin according to the Draize classification system. Systemic toxicity was not observed after dermal application of the test substance and the general condition of the animals was unaffected.

 

Based on the results of this study, the test material does not require classification as a skin irritant according to EU CLP criteria (EC 1272/2008).

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:
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
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
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
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
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
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
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
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1-72 hours
Score:
2.1
Max. score:
10
Reversibility:
fully reversible within: 11 days
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
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
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
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
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".

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
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).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

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, conducted according to GLP, 0.5 g of tetraammineplatinum(II) hydrogen carbonate (moistened with 0.14 mL water) was applied to the clipped skin of three male white Russian rabbits. After 4 hours, the occlusive dressings were removed and the skin sites assessed for signs of irritation (edema and erythema/eschar) at 1, 24, 48 and 72 hours. Erythema (including eschar) and edema (both very slight) were observed in one of the three animals after 48 and 72 hr respectively. Effects were reversible within 9 days of application. No signs of irritation were apparent in the other two animals. The test material produced a primary dermal irritation index of 0.3 [maximum total score = 8.0] (mean of scores at 1 -72 hr after application) and was classified as non-irritant to rabbit skin according to the Draize classification system. Systemic toxicity was not observed after dermal application of the test substance and the general condition of the animals was unaffected (Berthold, 1997b).

 

In an OECD guideline study (TG 405), conducted according to GLP, tetraammineplatinum(II) hydrogen carbonate (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 (Berthold, 1997c).

 

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 irritation study (in rabbits), tetraammineplatinum(II) hydrogen carbonate does not require classification for skin irritation according to EU CLP criteria (EC 1272/2008).

 

On the basis of the persistent effects in one animal in the available eye irritation study, the compound is therefore classified for serious eye damage (Category 1), in line with the harmonised classification according to Annex VI of the CLP regulation.