Dipotassium hexachloropalladate

Endpoint summary

Description of key information

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 (Zechel, 1989a).

In an OECD Guideline study, to GLP, undiluted dipotassium hexachloropalladate (90 mg) produced severe irritation and corrosive effects following instillation into the eye of one male rabbit (Zechel, 1989b).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

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

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.

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]

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.

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.

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).

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:

The study preparation and single ocular application took place between 19 April and 24 April 1989.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD Guideline study, to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Remarks:

no significant deviations.

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Remarks:

no significant deviations.

GLP compliance:

yes

Species:

rabbit

Strain:

other: White Russian (albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ASTA Pharma AG, D-4800 Bielefeld 14
- Age at study initiation: 8 months (male)
- Weight at study initiation: 2.58 kg
- 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/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): 20.5-23.5
- Humidity (%): 45-60
- 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”)

Vehicle:

unchanged (no vehicle)

Controls:

other: second eye of treated animals served as concurrent control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.09 g (volume of around 0.1 ml)

The test substance was applied to the conjunctival sac.

Duration of treatment / exposure:

Eyelids were briefly closed by gentle finger pressure, no subsequent washing to remove test substance.

Observation period (in vivo):

I hour

Number of animals or in vitro replicates:

One male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye was not rinsed

SCORING SYSTEM: Signs of irritation on the cornea, iris and conjunctiva should have been assessed qualitatively and quantitatively using the Draize scale following application of the test material into the eye, but weren't due to corrosive effects.

TOOL USED TO ASSESS SCORE: Cliptrix pencil light for examination in situ. Eye, lids and nictating membrane from treated eye were examined microscopically.

Irritation parameter:

overall irritation score

Reversibility:

other: reversibility was not assessed due to humane sacrifice of the animal one hour after application of the test substance.

Remarks on result:

other: An irritation index could not be determined because of the corrosive effects of the test substance.

Irritant / corrosive response data:

Corrosive effects were seen. The whole corneal area showed an easily discernible translucent opacity; detail of the iris were slightly obscured (grade 2) “without showing any alterations”; the nictating membrane was discoloured (yellow) and hardened and no reaction was seen on handling or mechanical opening of the palpebral fissure; discharge with moistening of considerable areas around the eye (grade 3).

Microscopic examination revealed severe superficial necrosis in the conjunctiva and deep acute coagulation necrosis in the nictating membrane. Slight to moderate oedema and slight inflammatory cell infiltration (predominantly neutrophilic granulocytes) were found in the conjunctiva and nictating membrane. In the cornea, acute coagulation necrosis of the corneal epithelium, focal complete loss of the necrotic corneal epithelium and hyalinization of superficial layers of the corneal stroma were seen.

See tables 1 and 2.

Other effects:

Systemic toxic effects were not observed.

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

In an OECD Guideline study, to GLP, undiluted dipotassium hexachloropalladate (90 mg) produced severe irritation and corrosive effects following instillation into the eye of one male rabbit.

Executive summary:

In an OECD Guideline study, to GLP, undiluted dipotassium hexachloropalladate (90 mg) was instilled into one eye of one rabbit and both lids were briefly closed by gentle finger pressure. The other eye remained untreated and acted as the control. Following application of the test material, severe changes indicative of a corrosive effect were seen within one hour that necessitated humane sacrifice of the animal. These included opacity and necrosis of the cornea, profuse ocular discharge and swelling and necrosis in the conjunctiva and nictitating membrane. An irritation index could not be determined because of the corrosive effects. No systemic toxicity was seen.

 

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 appropriate 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 human data were identified for irritation (for dipotassium or diammonium hexachloropalladate).  No in vitro skin or eye irritation studies were identified, or are required, as reliable in vivo studies are already available.

 

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” (Zechel, 1989a).

 

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

 

Neat dipotassium hexachloropalladate was not irritant when applied to the intact skin of rabbits in a limited, non-GLP, study (Campbell et al., 1975). This supports an EU CLP skin classification in category 2, as a health precautionary approach.

 

In an OECD Guideline study, to GLP, undiluted dipotassium hexachloropalladate (90 mg) was instilled into one eye of one rabbit and both lids were briefly closed by gentle finger pressure. The other eye remained untreated and acted as the control. Following application of the test material, severe changes indicative of a corrosive effect were seen within one hour that necessitated humane sacrifice of the animal. These included opacity and necrosis of the cornea, profuse ocular discharge and swelling and necrosis in the conjunctiva and nictitating membrane. An irritation index could not be determined because of the corrosive effects. No systemic toxicity was seen (Zechel, 1989b).

 

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 data were identified. A new study was not conducted as it is not a REACH Standard Information Requirement. Further, the compound is not expected to reach the lungs in appreciable quantities (based on respiratory tract deposition modelling data). Thus, inhalation will not be a significant route of exposure.

Justification for selection of skin irritation / corrosion endpoint:
GLP study, conducted according to OECD guidelines.

Justification for selection of eye irritation endpoint:
GLP study, similar to OECD guidelines, 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), dipotassium hexachloropalladate should be classified as a skin irritant (category 2) and for eye damage (category 1), according to EU CLP criteria (EC 1272/2008).