Platinum dioxide

Endpoint summary

Description of key information

Platinum dioxide was not irritant in a limited (pre-GLP) study, involving 24-hr occluded application to the intact and abraded skin of 6 male rabbits (Campbell et al., 1975).
In a guideline study, to GLP, instillation of platinum dioxide (0.1 g) produced moderate irritation in three rabbits after a 72-hr observation period (Allen, 1994).
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:

not stated in paper, but submitted for publication in 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Although the study is not conducted to a modern protocol and is somewhat limited, it is nevertheless fairly well documented and scientifically acceptable

Qualifier:

no guideline followed

Principles of method if other than guideline:

Dermal irritancy asessed using male albino rabbits using procedures and evaluation criteria adopted from those in use by the National Institute for Occupational Safety and Health, ... a modification of the official Food and Drug Administration procedure [1973]"

GLP compliance:

no

Species:

rabbit

Strain:

other: albino

Details on test animals or test system and environmental conditions:

no data

Type of coverage:

occlusive

Preparation of test site:

other: Pairs of test sites, each 2 cm x 2 cm, on the closely clipped dorsolaterals aspects of each animal, one side abraded and the other side intact

Vehicle:

water

Remarks:

0.1 ml

Controls:

yes, concurrent vehicle

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

24 hours

Observation period:

skin reactions scored immediately on removal of patch and 48 hours later

Number of animals:

Total of 6 rabbits, with up to 7 pairs of test sites each, used to test 14 test substances, some substances tested more than once

Details on study design:

Pairs of test sites, each 2 cm x 2 cm, on the closely clipped dorsolaterals aspects of each animal, one side abraded and the other side intact; Test substances in solid (powder) state were mixed with water (0.1 g quantity mixed with 0.1 ml deionised water) and spread over each site; after application of test substances [several probably tested simultaneously on each animal], test sites occluded; 24 hours later, coverings removed and test sites gently washed with soap, rinsed and dried; skin reactions scored immediately and 48 hours later; evaluation on a grading scale from 0 to 4 [similar to Draize scale]

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

single test rating or average of two or three

Time point:

other: 24 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: Severity rating for both intact and abraded skin sites

Irritant / corrosive response data:

Average skin reaction for 24 and 72 hours after the start of treatment calculated for intact and abraded skin [no individual scores or any further information presented in paper]

Interpretation of results:

not irritating

Conclusions:

Platinum dioxide was not irritant in a limited (pre-GLP) study, involving 24-hr occluded application to the intact and abraded skin of 6 male rabbits.

Executive summary:

In a pre-GLP study, the dermal irritancy of 14 materials, including platinum dioxide, was assessed in albino rabbits. Test materials, mixed with water, were applied to intact and abraded skin of 6 male albino rabbits as 24-hour occluded patches. Coverings were then removed and sites scored immediately and 48 hours later, using a scale from 0 (non-irritant) to 4 (corrosive).

Platinum dioxide failed to give any indication of irritation (score 0) on both intact and abraded skin (mean of reactions at 24 and 72 hours). No classification for skin irritancy is required according to EU CLP criteria (EC 1272/2008), based on the results of this study.

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:

not stated

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.75 - 3.29 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 21
- Humidity (%): 48 - 58
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To:

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye untreated and served as control

Amount / concentration applied:

100 mg/eye

Duration of treatment / exposure:

Test material placed into conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyball. Upper and lower eyelids were held together for about one second immediately after application and then released. Test material was not washed out.

Observation period (in vivo):

Grading timepoints: 1, 24, 48 and 72 hours
Reversibility assessed at 7 days

Number of animals or in vitro replicates:

One animal treated initially. After consideration of ocular response, two additional animals were treated.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: not applicable

SCORING SYSTEM:
Quantitative, using Draize scale (cornea: degree of opacity 0-4, area affected 1-4; iris 0-2; conjunctiva: redness 0-3, chemosis 0-4, discharge 0-3).
Interpretation using modified Kay and Calandra scheme (0-8 point irritation scale)

TOOL USED TO ASSESS SCORE: light source from standard ophthalmoscope

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48, 72 hours

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48, 72 hours

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48, 72 hours

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48, 72 hours

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 24, 48, 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: 24, 48, 72 hours

Score:

1.7

Max. score:

3

Reversibility:

not fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

other: 24, 48, 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48, 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48, 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48, 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Corrosive:No

Irritation Score: Cornea/Iris:
Cornea: at 24 and 48 hours - diffuse corneal opacity in 2/3 eyes (degree 1, area 1); no other corneal effects.
Iris: at 1 hour - iridial inflammation (1) in 3/3 eyes; 24 hours - iridial inflammation (1) in 2/3 eyes; no other iridial effects.

Irritation Score: Conjunctivae (Redness/Chemosis):
Conjunctivae: at 1 hour - moderate conjunctival irritation in 3/3 eyes (redness 2, chemosis 2, discharge 2); at 24 hours - minimal to moderate conjunctival irritation in 3/3 eyes (redness 2, chemosis 1-2, discharge 0-3); at 48 hours - minimal conjunctival irritation in 3/3 eyes (redness 1-2, chemosis 0-1, discharge 0); at 72 hours - minimal conjunctival irritation in 1/3 eyes (redness 1, chemosis 0, discharge 0); no other conjunctival effects.

Overall Irritation Score:
Highest overall irritation score 17.0, with group mean score at 72 hours >0; Kay and Callandra class 5, moderate irritant

3/3 animals affected.

Scores were reduced over time.

Effects were reversible.

Residual test material was found around the treated eye.

For Kay and Callandra classification, group mean scores (3 animals) for each timepoint:

1 hour - 17.0 (individual scores 17, 17, 17)

24 hours - 16.7 (individual scores 6, 24, 20)

48 hours - 7.3 (individual scores 2, 11, 9)

72 hours - 0.7 (individual scores 0, 2, 0)

7 days - 0 (1 animal)

Highest overall irritation score 17.0, with group mean score at 72 hours >0, placing the test material in class 5, moderate irritant.

For EC classification, mean scores (24, 48 and 72 hours) for individual animals:

Corneal opacity - 0.0, 0.7, 0.7

Iridial inflammation - 0.0, 0.3, 0.3

Conjunctival redness - 1.0, 1.7, 1.0

Conjunctival chemosis - 0.3, 1.0, 1.0

Test material does not meet the limits required by the EC regulation for hazard labelling.

Interpretation of results:

not irritating

Conclusions:

In a guideline study, to GLP, instillation of platinum dioxide (0.1 g) produced moderate irritation in three rabbits after a 72-hr observation period. The substance would not be classified under EU CLP criteria.

Executive summary:

In an OECD Test Guideline 405 study, conducted to GLP, the potential of platinum dioxide to cause eye irritation was assessed in rabbits. The test material (0.1 g) was instilled into the conjunctival sac of the right eye of each of three New Zealand White rabbits, without irrigation. Diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation were observed during the 72-hr observation period; only conjunctival redness had not reversed during this period (though it had lessened in severity). The test material produced a maximum group mean score of 17.0 and was classified as a moderate irritant (Class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. However, no classification for eye irritation is required based on EU CLP criteria (EC 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No relevant irritation/corrosion human data were identified.

 

In a pre-GLP study, the dermal irritancy of 14 materials, including platinum dioxide, was assessed in albino rabbits. Test materials, mixed with water, were applied to intact and abraded skin of 6 male albino rabbits as 24-hour occluded patches. Coverings were then removed and sites scored immediately and 48 hours later, using a scale from 0 (non-irritant) to 4 (corrosive). Platinum dioxide failed to give any indication of irritation (score 0) on both intact and abraded skin (mean of reactions at 24 and 72 hours) (Campbell et al., 1975).

 

In an OECD Test Guideline 405 study, conducted to GLP, the potential of platinum dioxide to cause eye irritation was assessed in rabbits. The test material (0.1 g) was instilled into the conjunctival sac of the right eye of each of three New Zealand White rabbits, without irrigation. Diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation were observed during the 72-hr observation period; only conjunctival redness had not reversed during this period (though it had lessened in severity). The test material produced a maximum group mean score of 17.0 and was classified as a moderate irritant (Class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system (Allen, 1994).

 

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

Justification for selection of skin irritation / corrosion endpoint:
US Guideline study, pre-GLP, and the only skin irritation study available.

Justification for selection of eye irritation endpoint:
OECD guideline study, and the only eye irritation study available.

Justification for classification or non-classification

Based on the results of the available skin and eye irritation studies in rabbits, platinum dioxide does not require classification for skin or eye irritation according to EU CLP criteria (EC 1272/2008).