Dipotassium hexachloropalladate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Remarks:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The single dermal application and the pre- and post- observation periods were between 06 April and 28 April 1989.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A OECD guideline study, to GLP. However, the data did not permit the calculation of a primary dermal irritation index; the degree of erythema could not be assessed due to discolouration of the skin by the test substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 003

Cas Number:

16919-73-6

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): potassium hexachloropalladate (IV)
- Substance type: red powder
- Physical state: solid
- Analytical purity: 26.8% Pd
- Impurities (identity and concentrations): no data
- Purity test date: Apparently 07 July 1989
- Lot/batch No.: 041368
- Expiration date of the lot/batch: no data
- Stability under test conditions: Stable
- Storage condition of test material: kept desiccated in a closed container in a fridge
- Other: “substance archives no.”: 87786

Test animals

Species:

rabbit

Strain:

other: White Russian (albino)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ASTA Pharma AG, D-4800 Bielefeld 14
- Age at study initiation: 6 months (single male); 7 or 10 months ( two females)
- Weight at study initiation: 2.55 kg (single male); 2.50 or 2.55 kg (two females)
- Housing: Stainless steel ASTA cages with grating floor, size 48.5(L)x40(B)x36.5(H) cm
- Diet (e.g. ad libitum): Approximately 120 g/animal/day of standard diet ssniff K “Special Diet for Rabbits”, supplied by ssniff Spezialfutter GmbH, D-4770 Soest
- Water (e.g. ad libitum): ad libitum from Stadtwerke Beilefeld (Municipal Works)
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-24
- Humidity (%): 40-60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12 (6 am- 6 pm: artificial lighting; 6 pm-6 am: “natural light-dark-rhythm”)

IN-LIFE DATES: From: To: no data

Test system

Type of coverage:

occlusive

Preparation of test site:

other: Backs of the rabbits were clipped one day before treatment.

Vehicle:

water

Remarks:

[demineralized; to moisten test material only]

Controls:

other: a comparable area of skin treated identically but without test substance served as concurrent control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.14 ml

Duration of treatment / exposure:

4 hours

Observation period:

10 days

Number of animals:

One male and two females

Details on study design:

TEST SITE
- Area of exposure: linen cloth covering application site was approximately 6.25 cm2
- Type of wrap if used: Acrylastic bandage, No. 2408, width 8 cm, supplied by P. Beiersdorf and Co. AG, Hamburg. This was placed over a linen cloth fixed with “a synthetic film glue” that covered the application site.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes – performed gently
- Time after start of exposure: 4 hours

SCORING SYSTEM: Oedema was evaluated qualitatively and quantitatively, according to the Draize method (see below, in “Any other information ...” section), at 1, 24, 48 and 72 hours after removal of the occlusive covering. Neither qualitative nor quantitative evaluation of erythema (and eschar formation) were possible because the test substance caused yellow-orange discolouration of the exposed skin area.

[Normally, erythema (and eschar formation) and oedema values for each animal and each time-point would be added. An “irritation index” would then be calculated by dividing by this value by the number of observations (in this case the number of observations would equal 12, the product of “4 time-points x 3 animals”). The study report notes that irritation indices of: up to 0.5 would indicate a non-irritant; 0.6-3.0 would indicate a slight irritant; 3.1-5.0 would indicate a moderate irritant; 5.1-8.0 would indicate a severe irritant].

Animals were assessed daily for the 10-day observation period for other skin reactions (such as corrosion) and clinical symptoms.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks on result:

other: [It was not possible to assess the degree of redness (erythema) resulting from exposure due to discolouration of the skin by the test substance]

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hours after termination of exposure

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: The maximum oedema score was seen in a single animal 24 hours post-application.

Irritant / corrosive response data:

Oedema was seen in all animals. It was very slight in two (in one, upon removal of the occlusive covering and persisting until day 6 of observation; in the other, at 24- and 48-hours post-exposure only). In the third animal, moderate oedema was seen at 24-hours post-exposure; this gradually reduced in severity until no oedema was apparent on day 7 of observation.

It was reported that a slight or moderate oedema [see Remarks, below] was seen beyond the boundary of the exposure site at one- and two-days post-exposure in a single animal [it was not clear which animal].

In two animals, skin scales formed but apparently peeled off “immediately” [presumably upon removal of the occlusive bandage].

The effects were considered by the authors to be of “only slight to moderate intensity”.

Other effects:

No systemic toxic effects were seen.

Any other information on results incl. tables

In their summary, the authors note that “slight erythema” beyond the area of exposure was seen in one animal. The authors' summary also reports “very slight or moderate to severe” oedema, but neither the results section nor the data table [Table 1, attached] report severe oedema in any of the animals at any time point.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an OECD Guideline study, to GLP, the irritant effect of dipotassium hexachloropalladate to the skin of rabbits was described as of “only slight to moderate intensity”. It was not possible to assess the degree of redness (erythema) resulting from exposure due to discolouration of the skin by the test substance, but the oedema score indicates that this is probably a reasonable conclusion.

Executive summary:

In a GLP skin irritation study in rabbits,conducted according to OECD Test Guideline 404, dipotassium hexachloropalladate (0.5 g, moistened) was applied (occluded) to the clipped but intact skin of one male and two female rabbits. After 4 hours, the dressings were removed and the skin sites gently washed. Each site was quantitatively assessed for oedema at 1, 24, 48 and 72 hours (and subsequently once/day up to 10 days post-application). Erythema and eschar formation could not be assessed quantitatively or qualitatively because the test material caused yellow or orange discolouration of the application site. Consequently the calculation of a primary irritation index was not possible.

The authors concluded that the irritant effects of this material were of “only slight to moderate intensity”.

 

Due to the skin site discolouration, it is not possible to give a definitive classification interpretation according to EU CLP criteria. However, it is considered precautionary to classify the test material as a skin irritant (Category 2), according to CLP criteria (EC 1272/2008).