Hexachloroplatinic acid

Endpoint summary

Description of key information

In three early studies (two to US guidelines), a single occluded application (4 or 24 hr) of hexachloroplatinic acid to the skin of rabbits induced necrosis 48 hr after removal of the patch, which was irreversible during the observation period (Middleton and Haynes, 1978; Nicholas and Jones, 1976; Nicholas and Jones, 1977).

 

No relevant eye or respiratory tract irritation data were identified. However, such testing is not appropriate ashexachloroplatinic acidis classified as corrosive to the skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation / corrosion, other

Remarks:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Early guideline study (US Department of Transportation), prior to GLP, scientifically acceptable

Qualifier:

according to guideline

Guideline:

other: US Code of Federal Regulation, Title 49, Part 173, Appendix A, 27th September, 1976, Department of Transportation

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Healthy female rabbits from "recognised breeders"
- Age at study initiation: 16 - 18 weeks
- Weight at study initiation: mean 2.5 kg
- Housing: caged in environmentally controlled room
- Diet (e.g. ad libitum): commercial rabbit diet (Rank Hovis MacDougal)
- Water (e.g. ad libitum): filtered, ad libitum
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not stated
- Humidity (%): not stated
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): natural lighting

IN-LIFE DATES: From: To:

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Remarks:

test material applied as supplied (crystalline material)

Controls:

no

Amount / concentration applied:

0.5 g/test site

Duration of treatment / exposure:

4 hours

Observation period:

Assessed for necrosis and ulceration, immediately after the end of treatment (4 hours) and at 48 hours and 7 days after the start of treatment.

Number of animals:

6

Details on study design:

Area of the back of each rabbit (at least 10% of body surface) was shaved 24 hours prior to treatment. One test site over the mid-line on each rabbit. 0.5 g test material applied to each test site on a gauze pad 2.5 x 2.5 cm. Pads secured with occlusive tape and dressings and left in place for 4 hours.

Assessed for necrosis and ulceration, immediately after the end of treatment (4 hours) and at 48 hours and 7 days after the start of treatment.

No control sites or animals were incorporated into the test

Criteria for classification as corrosive included destruction or irreversible alteration of the tissue, where tissue destruction involved ulceration or necrosis at any reading, not merely sloughing of the epidermis, erthyema, oedema or fissuring.

Irritation parameter:

other: assessment for corrosivity

Basis:

other: assessment of necrosis and ulceration in 6 rabbits

Time point:

other: 4 hours, 48 hours, 7 days

Reversibility:

not reversible

Remarks on result:

positive indication of irritation

Remarks:

Irritation was observed at the 4-hr time point in four animals. After 48 hr this had developed into necrosis in five animals, which was still evident at the end of the observation period. One animal was unaffected by treatment at every time point.

Irritant / corrosive response data:

One animal was unaffected by treatment at every timepoint.
Results from the remaining 5:
At 4 hours, 4/5 animals had skin irritation and 1/5 was unaffected.
At 48 hours, 5/5 animals had at least 1 area of necrotic tissue.
At 7 days, necrosis was maintained in 5/5 animals.

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: other: US Federal Register Corrosivity Test (1976)

Conclusions:

In an early US guideline study, irreversible necrosis was observed following a single 4-hr occluded application of chloroplatinic acid to the skin of six rabbits.

Executive summary:

In an early US guideline study, the skin irritant potential of chloroplatinic acid was assessed in six female New Zealand White rabbits. The test material (0.5 g, crystalline solid) was applied to shaved intact skin for 4 hr under occlusion. The sites were assessed for evidence of necrosis or ulceration immediately upon removal of the patch, with further assessments made at 48 hours and 7 days after application of the test material.

 

Irritation was observed at the 4-hr time point in four animals. After 48 hr this had developed into necrosis in five animals, which was still evident at the end of the observation period. One animal was unaffected by treatment at every time point.

 

Based on the results of this study, the test material should be classified as corrosive to skin (at least category 1C) under EU CLP criteria (EC 1272/2008).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Early guideline study (US EPA), prior to GLP, scientifically acceptable

Qualifier:

according to guideline

Guideline:

other: US EPA (Skin irritation patch test, Federal Register, 38(187), 1500:41, 1973)

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Healthy female rabbits from "recognised breeders"
- Age at study initiation: 12-14 wk
- Weight at study initiation: mean 2.29 kg
- Housing: caged singly
- Diet (e.g. ad libitum): commercial rabbit diet (Rank Hovis MacDougal)
- Water (e.g. ad libitum): filtered ad libitum


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:

Type of coverage:

occlusive

Preparation of test site:

other: shaved; 1 intact & 1 abraded site/animal

Vehicle:

other: CB12-dry: no vehicle; CB12-humid: no vehicle but powdered material allowed to stand for 1 hr at 18 deg C & 61% humidity

Controls:

no

Amount / concentration applied:

0.5 mg/test site [as stated in study report, but the usual amount is 0.5 g]

Duration of treatment / exposure:

24 hours

Observation period:

Assessed for oedema and erythema immediately after the end of treatment (24 hours) and 48 hours later (72 hours).

Number of animals:

6

Details on study design:

Area of the back of each rabbit (at least 10% of body surface) was shaved 24 hours prior to treatment. Two lateral test sites on each rabbit, one abraded immediately prior to treatment. 0.5 mg [sic] test material applied to each test site on a gauze pad 2.5 x 2.5 cm. Pads secured with occlusive tape and dressings and left in place for 24 hours.

Assessed for oedema and erythema immediately after the end of treatment (24 hours) and 48 hours later (72 hours). Primary irritation index calculated and classified using method of Draize (1959).

No control sites or animals were incorporated into the test.

Difficulty was encountered in applying the sample in its dry form as it could be seen to be taking up water after a few seconds exposure to the atmosophere immediately prior to application.

Irritation parameter:

primary dermal irritation index (PDII)

Remarks:

CB12 Dry

Basis:

mean

Remarks:

6 rabbits

Time point:

other: 24 & 72 hr

Score:

6.62

Max. score:

8

Reversibility:

not reversible

Irritation parameter:

primary dermal irritation index (PDII)

Remarks:

CB12 Humid

Basis:

mean

Remarks:

6 rabbits

Time point:

other: 24 & 72 hr

Score:

7.17

Max. score:

8

Reversibility:

not reversible

Irritant / corrosive response data:

CB12-dry total scores presented in study report for 6 animals at 2 timepoints:
erythema: 43 (abraded), 33 (intact); [max 48]
oedema: 45 (abraded), 38 (intact); [max 48]
average score: 26.5; [max 32]
all treatment sites had necrotic areas at both timepoints

CB12-humid total scores presented in study report for 6 animal at 2 timepoints:
erythema: 44 (abraded), 41 (intact); [max 48]
oedema: 47 (abraded), 40 (intact); [max 48]
average score: 28.7; [max 32]
all treament areas were necrotic at both timepoints

Interpretation of results:

other: described as a severe irritant

Remarks:

Criteria used for interpretation of results: other: JH Draize "Apraisal of the Safety of Chemicals in Food, Drugs and Cosmetics" 1959

Conclusions:

In an early US guideline study, a 24-hr occluded application of chloroplatinic acid (both dry and humid forms) produced severe irritation and necrosis to the skin of rabbits, the latter producing more severe effects, which was irreversible during the 48-hr observation period.

Executive summary:

In a US EPA guideline study, chloroplatinic acid (in dry and humid forms) was applied to the intact and abraded skin of six female New Zealand White rabbits as a 24-hr occluded patch. [The dose applied was specified as 0.5 mg, though 0.5 g is commonly tested]. The test sites were assessed for erythema and oedema immediately on removal of the patch, and 48 hr later.

 

Severe irritation and necrosis was observed in all animals and there was little or no sign of reversibility at the end of the observation period. The total area of necrosis was considerably greater following application of the humid sample.

 

Based on the results of this study, the test material should be classified as corrosive to skin (at least category 1C) under EU CLP criteria (EC 1272/2008).

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles

Qualifier:

no guideline followed

Principles of method if other than guideline:

Skin irritation assessed by applying 24-hour covered patches to the shaved skin of 4 rabbits. Oedema and erythema scored at removal of patch (24 hr) and 48 hours later (72 hours).

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Healthy female rabbits from "recognised breeders"
- Age at study initiation: 16-18 weeks
- Weight at study initiation: 2.1 kg
- Housing: Individually caged in an experimental room.
- Diet (e.g. ad libitum): Ad libitum commercial rabbit diet (Rank Hovis MacDougal)
- Water (e.g. ad libitum): Filtered 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

IN-LIFE DATES: From: To: No data

Type of coverage:

occlusive

Preparation of test site:

other: shaved; 1 intact and 1 abraded test site/animal

Vehicle:

other: presumably water

Controls:

no

Amount / concentration applied:

0.5 ml/test site,
1 intact and 1 abraded test site/animal

Duration of treatment / exposure:

24 hours

Observation period:

Assessed for oedema and erythema immediately after the end of treatment (24 hours) and 48 hours later (72 hours). Primary irritation index calculated and classified using method of Draize (1959).

Number of animals:

4

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Remarks:

4 rabbits

Time point:

other: 24, 72 hours

Score:

3.2

Max. score:

8

Reversibility:

not fully reversible within: 72 hours

Irritant / corrosive response data:

Total scores presented in study report for 4 animals at 2 timepoints:
erythema: 10 (abraded), 16 (intact); [max 32]
oedema: 12 (abraded), 13 (intact). [max 32]
Average scores: erythema 6.5, oedema 6.3, overall 12.8;
3/4 abraded and 3/4 intact sites had necrotic areas at both timepoints.

Interpretation of results:

other: moderate to severe irritation; corrosive

Remarks:

Criteria used for interpretation of results: other: JH Draize "Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics" 1959

Conclusions:

In a non-guideline skin irritation study, chloroplatinic acid solution produced moderate to severe erythema and oedema, as well as necrosis, after a 24-hr occluded application to the skin of rabbits.

Executive summary:

In a non-guideline skin irritation study, a 2% solution of chloroplatinic acid solution (0.5 ml) was applied to the intact and abraded skin of four female New Zealand White rabbits as a 24-hr occluded patch. The test sites were assessed for erythema and oedema immediately on removal of the patch, and 48 hr later.

 

Moderate to severe erythema and oedema, along with necrosis, were observed in all four animals. A Primary Irritation Score of 3.2 (out of 8) was obtained.

 

Based on the results of this study, the test material should be classified as corrosive to skin (at least category 1C) under EU CLP criteria (EC 1272/2008).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

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

 

In a US Federal Register Corrosivity Test (1976), the skin irritant potential of chloroplatinic acid was assessed in six female New Zealand White rabbits. The test material (0.5 g, crystalline solid) was applied to shaved intact skin for 4 hr under occlusion. The sites were assessed for evidence of necrosis or ulceration immediately upon removal of the patch, with further assessments made at 48 hours and 7 days after application of the test material. Irritation was observed at the 4-hr time point in four animals. After 48 hr this had developed into necrosis in five animals, which was still evident at the end of the observation period. One animal was unaffected by treatment at every time point (Middleton and Haynes, 1978).

 

In a US EPA guideline study, chloroplatinic acid (in dry and humid forms) was applied to the intact and abraded skin of six female New Zealand White rabbits as a 24-hr occluded patch. [The dose applied was specified as 0.5 mg, though 0.5 g is commonly tested]. The test sites were assessed for erythema and oedema immediately on removal of the patch, and 48 hr later. Severe irritation and necrosis was observed in all animals and there was little or no sign of reversibility at the end of the observation period. The total area of necrosis was considerably greater following application of the humid sample (Nicholas and Jones, 1976).

 

In a non-guideline skin irritation study, a 2% solution of chloroplatinic acid solution (0.5 ml) was applied to the intact and abraded skin of four female New Zealand White rabbits as a 24-hr occluded patch. The test sites were assessed for erythema and oedema immediately on removal of the patch, and 48 hr later. Moderate to severe erythema and oedema, along with necrosis, were observed in all four animals. A Primary Irritation Score of 3.2 (out of 8) was obtained (Nicholas and Jones, 1977).

No eye or respiratory tract data were identified. However, eye irritation testing is not considered appropriate as hexachloroplatinic acidis classified as corrosive to the skin.

Justification for classification or non-classification

Based on the results of the available reliable in vivo skin irritation studies in rabbits, hexachloroplatinic acid should be classified as corrosive to the skin (at least category 1C) according to EU CLP criteria (EC 1272/2008). However, hexachloroplatinic has a harmonised classification as skin corrosive (category 1B) according to Annex VI of the CLP regulation. As such, this classification is adopted here.

 

Substances that are corrosive to the skin are considered as leading to serious damage to the eyes. Consequently, hexachloroplatinic acid should be classified for eye effects in Category 1 according to EU CLP criteria (EC 1272/2008).