Registration Dossier

Administrative data

Description of key information

In two early US guideline studies, sodium and ammonium hexachloroplatinate (each 0.5 g) were applied (24-hr, occluded) to the shaved abraded and intact skin of groups of six rabbits. No evidence of irritation to intact skin was observed during the observation period following application of sodium hexachloroplatinate (Middleton, 1978a). The ammonium salt induced slight but reversible indications of irritation to intact skin in three animals during the observation period (Middleton, 1978b).

 

In a guideline study, to GLP, potassium hexachloroplatinate produced corrosive effects following instillation into the eye of a single male rabbit (Berthold, 1995b).

 

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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study apparently performed according to the method described in Federal Register 1973, Vol. 38, No. 187, Section 1500: 41, which has some significant deviations from current OECD guidelines.
Qualifier:
according to
Guideline:
other: Skin irritation patch test, as described in Federal Register 1973, Vol. 38, No. 187, Section 1500: 41.
Deviations:
not specified
Principles of method if other than guideline:
0.5 g of material was applied on a gauze pad to abraded and non-abraded skin of six albino rabbits. The site was covered with adhesive tape. The sites were examined after 24 and 72 hours for erythema and oedema.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: “recognised breeders”
- Age at study initiation: 14-16 weeks
- Weight at study initiation: 2.2 kg (average)
- Diet: ad libitum commercial rabbit diet from Rank Hovis MacDougal
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): “Natural lighting conditions”
Type of coverage:
occlusive
Preparation of test site:
other: Backs of the rabbits were shaved (not “closely clipped” as recommended by the OECD guidelines). One site of each rabbit was abraded immediately before application of the test material, the other site remained intact.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
24 hrs
Observation period:
48 hrs
Number of animals:
Six females
Details on study design:
TEST SITE
- Area of exposure: Each site 2.5 cm2 (one intact, one abraded)
- Type of wrap if used: Gauze pad was secured by “Sleek” tape (evidently a waterproof tape)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None

SCORING SYSTEM: Erythema (and eschar) formation and oedema formation were assessed on the intact and abraded skin of six rabbits at 24 and 72 hrs after initial application of the test compound (i.e. as soon as the dressing was removed and again 48 hrs later). The primary irritation index was calculated by adding the four values for erythema (and eschar) formation to the four for oedema formation, and dividing the total by four. According to the study report, Draize (1959) considers that “compounds producing combined averages (primary irritation indices) of 2 or less are only mildly irritating; whereas those with indices of 2 to 5 are moderate irritants, and those with scores above 6 are considered severe irritants”.

Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hrs after initial application
Score:
0.5
Max. score:
8
Reversibility:
other: Reversibility not assessed, as observation period only 48 hrs (not up to 14 days as recommended in the OECD guidelines)
Other effects:
“Three abraded sites showed local areas of necrosis where the sample had entered abrasions on the epidermis. The systemic toxicity was not reported.

Table: Individual scores for each time point

 Animal number  Time/hr  Erythema     Oedema   
     Abraded skin Intactskin  Abraded skin  Intact skin
 1  24  0  0  0  0
   72  0  0  0  0
 2  24  1N  0  0  0
   72  2N  0  1  0
 3  24  0  0  0  0
   72  0  0  0  0
 4  24  0  0  0  0
   72  1N  0  1  0
 5  24  0  0  0  0
   72  0  0  0  0
 6  24  1N  0  1  0
   72  2N  0  2  0

N: Local areas of necrosis where the sample has entered abrasions on the epidermis

Interpretation of results:
GHS criteria not met
Conclusions:
In an early US guideline study, sodium hexachloroplatinate (0.5 g) was applied (24-hr, occluded) to the shaved abraded and intact skin of six rabbits. No evidence of irritation to intact skin was observed during the observation period.
Executive summary:

In a US Federal Register Patch Test (1973), the skin irritant potential of sodium hexachloroplatinate was assessed in six female New Zealand White rabbits. The test material (0.5 g) was applied (occluded) to the shaved abraded and intact skin for 24 hr.The sites were assessed for evidence of erythema (and eschar) formation and oedema formation immediately upon removal of the patch, and again 48 hr later.

 

The intact skin sites displayed no evidence of erythema/oedema at either time point. Three abraded sites showed evidence of possible necrosis associated with the abrasions in the skin.A Primary Irritation Score of 0.5 (out of 8) was obtained. The study authors classified sodium hexachloroplatinate as a mild skin irritant in this test system

 

This study suffered from a number of significant deviations from those given in the current OECD guidelines, including use of abraded skin, no moistening of test substance (a powder) to ensure good skin contact, a longer exposure period and failure to wash off any residual test material after removal of patch, observation period was insufficient to assess reversibility of effects, and skin was only examined on 2 occasions, at 0 and 48 hrs, rather than at 1, 24, 48 and 72 hrs, after patch removal. However, certain of these deviations are likely to increase the possibility of an irritant reaction.

 

Based on the results of this study, no classification for skin irritation is required under EUCLP 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:
15 March 1995 - 17 May 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with no protocol deviations
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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: 34 months
- Weight at study initiation: 2.81 Kg
- Housing: Stainless steel cage with grating floor
- Diet (e.g. ad libitum): Approx. 120 g/day standard diet
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5
- Humidity (%): 53-69
- Air changes (per hr) not stated:
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To:
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
99.5 mg
Duration of treatment / exposure:
Substance applied to conjunctival sac of left eye and both lids briefly closed by gentle finger pressure. The treated eye was not rinsed.
Observation period (in vivo):
1 and 24 hours after application
Number of animals or in vitro replicates:
1 male
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: not applicable

SCORING SYSTEM: Draize scale. An irritation index was not determined because of corrosive effects

TOOL USED TO ASSESS SCORE: Cliptrix pencil light
Remarks on result:
positive indication of irritation
Remarks:
Irritation index not determined because of corrosive effects
Irritant / corrosive response data:
Cornea: at 1 hour - no corneal opacity (degree 0, area 0); at 24 hours - corneal opacity (degree 4, area 4)
Iris: at 1 hour - no iridial irritation (0); at 24 hours - iris not discernible

Conjunctiva: at 1 hour - redness 2, chemosis 1, discharge 3; at 24 hours - redness 3 (diffuse beefy redness), chemosis 4 (swelling with lids more than half closed), discharge 3 (moistened considerable areas around the eye)

Eye filled with white mucus; eye, including nictitating membrane, discoloured (grey)

1 animal affected; due to the severity of the symptoms, no additional animals were tested.
Due to the severity of the symptoms at 24 hours, the tested animal was humanely killed.
Other effects:
Eye processed for microscopic examination: revealed evidence of inflammation in the iris, uvea and sclera, anterior chamber, cornea, ocular muscles and eyelids; pronounced corrosive effects leading to ulcerations, coagulation necrosis and inflammatory changes.

No systemic toxic effects detected.

No changes were seen in the untreated eye.
Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a guideline study, to GLP, potassium hexachloroplatinate produced corrosive effects following instillation into the eye of a single male rabbit.
Executive summary:

In an OECD Test Guideline 405 study, conducted according to GLP, potassium hexachloroplatinate (99.5 mg) wasinstilled into the conjunctival sac of the left eye ofa single male White Russian rabbit.The other eye was untreated to serve as a control. Following instillation the eyelids were held closed by gentle finger pressure.The ocular response was assessed at 1 and 24 hr after instillation; corneal opacity, effects on the iris and conjunctival redness, chemosis and discharge were scored according to the Draize numerical scale. The treated eye as well as eye lids and nictitating membrane were assessed microscopically.

 

Corrosive effects were noted following instillation of the test material. The cornea was opaque and the iris was not discernible through the opacity. The conjunctiva showed diffuse beefy redness and swelling with lids more than half to completely closed. Discharge moistened considerable areas around the eye. The histological findings revealed a pronounced corrosive potential. The animal was humanely killed after 24 hr and no additional animals were tested due to the severity of the symptoms.No evidence of systemic toxicity was observed.

 

As the results were based on only one rabbit, it is not possible to give a definitive interpretation according to EU CLP criteria (EC 1272/2008). However, it is considered prudent to classify the test material for serious eye damage (Category 1), as the severe effects observed are not expected to be reversible.

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 a US Federal Register Patch Test (1973), the skin irritant potential of sodium hexachloroplatinate was assessed in six female New Zealand White rabbits. The test material (0.5 g) was applied (occluded) to the shaved abraded and intact skin for 24 hr. The sites were assessed for evidence of erythema (and eschar) formation and oedema formation immediately upon removal of the patch, and again 48 hr later. The intact skin sites displayed no evidence of erythema/oedema at either time point. Three abraded sites showed evidence of possible necrosis associated with the abrasions in the skin. A Primary Irritation Score of 0.5 (out of 8) was obtained. The study authors classified sodium hexachloroplatinate as a mild skin irritant in this test system (Middleton, 1978a).

 

In an analogous guideline study, involving identical conditions with ammonium hexachloroplatinate, three intact skin sites showed evidence of erythema/oedema which was observed to be reversible (or showed indications of reversibility) during the observation period. No signs of irritation were apparent on the other three intact sites. Two abraded skin sites showed evidence of possible necrosis associated with the abrasions in the skin. A Primary Irritation Score of 1.3 (out of 8) was obtained. The study authors classified ammonium hexachloroplatinate as a mild skin irritant in this test system (Middleton, 1978b).

 

These two studies suffered from a number of significant deviations from those recommended in the current OECD guidelines, including use of abraded skin, no moistening of test substance (a powder) to ensure good skin contact, a longer exposure period and failure to wash off any residual test material after removal of patch, observation period was insufficient to assess reversibility of effects, and skin was only examined on 2 occasions, at 0 and 48 hrs, rather than at 1, 24, 48 and 72 hrs, after patch removal. However, certain of these deviations are likely to increase the possibility of an irritant reaction, so the study can be considered as likely more sensitive than the current methodology to identify potential irritants.

Diammonium and disodium hexachloroplatinate are considered to fall within the scope of the read-across category "hexachloroplatinate(IV) compounds". See section 13 in IUCLID for full read-across justification report.

 

In an OECD Test Guideline 405 study, conducted according to GLP, potassium hexachloroplatinate (99.5 mg) was instilled into the conjunctival sac of the left eye of a single male White Russian rabbit. The other eye was untreated to serve as a control. Following instillation the eyelids were held closed by gentle finger pressure. The ocular response was assessed at 1 and 24 hr after instillation; corneal opacity, effects on the iris and conjunctival redness, chemosis and discharge were scored according to the Draize numerical scale. The treated eye as well as eye lids and nictitating membrane were assessed microscopically. Corrosive effects were noted following instillation of the test material. The cornea was opaque and the iris was not discernible through the opacity. The conjunctiva showed diffuse beefy redness and swelling with lids more than half to completely closed. Discharge moistened considerable areas around the eye. The histological findings revealed a pronounced corrosive potential. The animal was humanely killed after 24 hr and no additional animals were tested due to the severity of the symptoms. No evidence of systemic toxicity was observed (Berthold, 1995b).

 

As the results were based on only one rabbit, it is not possible to give a definitive interpretation according to EU CLP criteria (EC 1272/2008). However, it is considered prudent to classify the test material for serious eye damage (Category 1), as the severe effects observed are not expected to be reversible.

 

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 studies (in rabbits) with the disodium and diammonium hexachloroplatinate salts, dipotassium hexachloropalladate does not require classification for skin irritation according to EU CLP criteria (EC 1272/2008).

 

Based on the results of the available and reliable eye irritation study in rabbits, dipotassium hexachloropalladate should be classified for eye damage (category 1), according to EU CLP criteria (EC 1272/2008).