Palladium dichloride

Endpoint summary

Description of key information

In a guideline study, to GLP, palladium dichloride applied to the clipped skin of three rabbits (4-hr semi-occluded) produced a primary irritation index of 3 and was considered as a moderate irritant according to the Draize classification system. No corrosive effects were noted (Allen, 1994b). However, as the test material produced “positive criteria” in only 1 of 3 rabbits according to the EU CLP criteria (i.e. a mean grade of >2.3 at the 24, 48 and 72 hr times for oedema in one animal only), classification as a skin irritant is not required.

According to an expert review of an early unpublished eye irritation study, conducted to US guidelines (CFR 21, part 191 12), a single instillation of palladium dichloride (100 mg) to the eyes of six rabbits produced irreversible effects (Hysell et al., 1974).

No relevant respiratory tract 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:

21 February to 28 February 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD), to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

No untreated (control) areas; no evidence that systemic adverse effects were recorded.

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

No untreated (control) areas; no evidence that systemic adverse effects were recorded.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.3-2.5 kg
- Housing: Individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 49-56
- Air changes (per hr): 15 changes
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

no

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): 0.5 ml

Duration of treatment / exposure:

Single 4 hour exposure

Observation period:

7 days

Number of animals:

3 (1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- % coverage:
- Type of wrap if used: The patch was secured with a strip of surgical adhesive tape (2.5 cm x 4 cm), and the trunk of each rabbit wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test material removed by gentle swabbing with cotton wool soaked in distilled water followed by diethyl ether
- Time after start of exposure: 4 hr

SCORING SYSTEM: The treated skin area was qualitatively and quantitatively scored using the Draize method at 1, 24, 48, and 72 hrs following removal of the patches (see OECD guidelines for grading of skin reactions). The primary irritation index is given by the sum of the values for erythema and oedema at the 24 and 72-hr readings and divided by 6.
Primary irritation index Classification
0 non-irritant
>0-2 mild irritant
>2-5 moderate irritant
>5-8 severe irritant
In addition, attention was paid to the occurrence of other skin reactions and irreversible alteration of the dermal tissue (which would lead to a classification of corrosive effects); systemic toxic effects were evidently not assessed.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hrs

Score:

ca. 3

Max. score:

8

Reversibility:

fully reversible within: 7 days (for erythema/ oedema), although crust formation and desquamation seen on day 7

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24, 48 and 72 hr

Score:

3.2

Max. score:

8

Reversibility:

fully reversible within: 7 days (for erythema/ oedema), although crust formation and desquamation seen on day 7

Irritant / corrosive response data:

Very slight to well-defined erythema was noted in all three rabbits assessed at 1, 24, 48 and 72 hr after patch removal. Very slight (1 animal) to slight oedema (2 animals) was noted 1 hour after patch removal, with very slight to moderate oedema at the 24- and 48-hr observations. Very slight (1 animal), slight (1 animal), or no oedema (1 animal) was seen at the 72-hr observation.

Skin reactions noted in all three rabbits 7 days after treatment were crust formation and desquamation. No corrosive effects were noted.

Other effects:

No data

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guideline study, to GLP, palladium dichloride applied to the clipped skin of three rabbits (4-hr semi-occluded) produced a primary irritation index of 3 and was considered as a moderate irritant according to the Draize classification system. No corrosive effects were noted. However, as the test material produced “positive criteria” in only 1 of 3 rabbits according to the EU CLP criteria (i.e. a mean grade of >2.3 at the 24, 48 and 72 hr time for oedema in one animal only), classification as a skin irritant is not required.

Executive summary:

Palladium dichloride was investigated for irritant (and corrosive) effects following 4-hr (semi-occluded) application (0.5 g), moistened with 0.5 ml distilled water, to the clipped skin of three New Zealand white rabbits (one male and two females) in accordance with OECD Test Guideline 404 (with slight deviations), and to GLP. Following removal of the patch (and residual test material), the sites were observed for signs of erythema and oedema at 1, 24, 48 and 72 hrs using the Draize grading scores. The test site was again assessed at day 7; no untreated site (as recommended by the OECD) was apparently assessed.

Very slight to well-defined erythema and very slight to moderate oedema were seen. Crust formation or desquamation were observed on all three animals 7 days after treatment. The test material produced a primary irritation index of 3 (from the mean of the 24- and 72 -readings) and was considered as a moderate irritant according to the Draize classification system. No corrosive effects were noted.

However, as the test material produced “positive criteria” in only 1 of 3 rabbits according to the EU CLP criteria (i.e. a mean grade of >2.3 at the 24-, 48- and 72-hr time for oedema in one animal only), classification as a skin irritant is not required.

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:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study (US CFR), pre-GLP, with limited reporting.

Qualifier:

according to guideline

Guideline:

other: CFR 21, part 191 12 (revised as of April 1, 1973)

Deviations:

no

GLP compliance:

no

Remarks:

(prior to GLP)

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Albino rabbits with no known ocular abnormalities.

Vehicle:

not specified

Controls:

other: The left eye of each animal served as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg (deposited on the eye surface)

Duration of treatment / exposure:

Presumably the observation period

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE: Not removed

SCORING SYSTEM: No data

TOOL USED TO ASSESS SCORE: No data

Irritation parameter:

other: Number of animals showing irritant reactions

Basis:

other: Total number of test animals

Time point:

other: 24 hours

Score:

6

Max. score:

6

Reversibility:

not reversible

Irritation parameter:

other: Number of animals showing irritant reactions

Basis:

other: Total number of test animals

Time point:

other: 48 hours

Score:

6

Max. score:

6

Reversibility:

not reversible

Irritation parameter:

other: Number of animals showing irritant reactions

Basis:

other: Total number of test animals

Time point:

other: 72 hours

Score:

6

Max. score:

6

Reversibility:

not reversible

Irritant / corrosive response data:

All six animals receiving palladium dichloride showed corrosive conjunctival lesions and severe inflammation of the cornea and anterior chamber of the eye.

Other effects:

No data

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to an expert review of an early unpublished eye irritation study, conducted to US guidelines (CFR 21, part 191 12), a single instillation of palladium dichloride (100 mg) to the eyes of six rabbits produced irreversible effects.

Executive summary:

According to an expert review of an early unpublished eye irritation study, conducted to US test guidelines (CFR 21, part 191 12), palladium dichloride (100 mg) was instilled into one eye of each of six rabbits. The other eye remained untreated and acted as the control. The treated eye was then assessed for ocular inflammation 24, 48 and 72 hr after application. All six animals showed severe conjunctival lesions and severe inflammation of the cornea and anterior chamber of the eye. The effects persisted throughout the observation period indicating that the test material induced irreversible effects on the eye.

 

Based on the results of this study, palladium dichloride should be classified as Category 1 (irreversible effects on the eye) according to EU CLP criteria (EC 1272/2008).

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 guideline study, to GLP, palladium dichloride applied to the clipped skin of three rabbits (4-hr semi-occluded) produced a primary irritation index of 3 and was considered as a moderate irritant according to the Draize classification system. No corrosive effects were noted (Allen, 1994b). However, as the test material produced “positive criteria” in only 1 of 3 rabbits according to the EU CLP criteria (i.e. a mean grade of >2.3 at the 24, 48 and 72 hr times for oedema in one animal only), classification as a skin irritant is not required.

 

In support, palladium dichloride was not irritant in a limited (pre-GLP) study, involving 24-hr occluded application to the intact skin of 6 male rabbits. To abraded skin, it caused at most only a mild irritant reaction (Campbell et al., 1975).

 

According to an expert review of an early unpublished eye irritation study, conducted to US test guidelines (CFR 21, part 191 12), palladium dichloride (100 mg) was instilled into one eye of each of six rabbits. The other eye remained untreated and acted as the control. The treated eye was then assessed for ocular inflammation 24, 48 and 72 hr after application. All six animals showed severe conjunctival lesions and severe inflammation of the cornea and anterior chamber of the eye. The effects persisted throughout the observation period indicating that the test material induced irreversible effects on the eye. Based on the results of this study, palladium dichloride should be classified for eye damage as Category 1 (irreversible effects on the eye) according to EU CLP criteria (EC 1272/2008).

 

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:
OECD guideline study, to GLP.

Justification for selection of eye irritation endpoint:
US Guideline study and the only eye irritation study available.

Justification for classification or non-classification

Based on the results of the available in vivo skin and eye irritation studies, palladium dichloride should not be classified as irritant/corrosive to the skin, but should be classified for ‘irreversible effects on the eye’ (category 1), according to EU CLP criteria (EC 1272/2008).