Diammonium hexachloropalladate

Endpoint summary

Description of key information

In a GLP skin irritation study in rabbits, equivalent to OECD Test Guideline 404, undiluted diammonium hexachloropalladate produced moderate skin irritation (Guest, 1989a). In support, neat diammonium hexachloropalladate was strongly irritant in a limited, non-GLP, rabbit study (Campbell et al., 1975).

In a GLP eye irritation study, equivalent to OECD Test Guideline 405, undiluted diammonium hexachloropalladate (100 mg) produced very severe eye irritation following instillation into the eye of one male rabbit (Guest, 1989b).

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:

30 August 1989 – 6 September 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to a company standard protocol designed to comply with the recommendations of OECD guideline No. 404

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

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: approx. 12-16 weeks
- Weight at study initiation: 2.68-2.96 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum Rabbit Diet supplied by Preston Farmers Limited, New Leake, Boston, Lincolnshire, UK
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-20
- Humidity (%): 60-70
- Air changes (per hr): approx. 15/hr
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Type of coverage:

semiocclusive

Preparation of test site:

other: test site clipped free of fur, described as “shorn skin”

Vehicle:

water

Controls:

no

Amount / concentration applied:

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

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Purity: distilled

Duration of treatment / exposure:

4 hrs

Observation period:

Approximately 1, 24, 48 and 72 hrs after removal of the patch

Number of animals:

One female and two males

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm2
- Type of wrap if used: A gauze patch secured with a strip of surgical adhesive tape (BLENDERM, approx 2.5 x 4.0 cm) and an elasticated corset (TUBIGRIP) wrapped around the trunk.

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

SCORING SYSTEM: The test sites were examined for evidence of primary irritation approximately 1 hr following removal of the patch and 24, 48 and 72 hrs later and scored according to the method of Draize (1959). An additional observation was made on day 7. The scores for erythema (and eschar) formation and oedema formation at the 24 and 72 hr observation times were totalled for the three rabbits (12 values) and divided by 6 to give the primary irritation index. This was then used to classify the skin irritation properties of the test material according to:

Primary Irritation Index Classification
0 Non-irritant
>0 – 2 Mild irritant
>2 – 5 Moderate irritant
>5 – 8 Severe irritant

The results were also interpreted according to EEC Directive 83/467/EEC adapting Council Directive 67/548/EEC on the regulations relating to the classification, packaging and labelling of dangerous substances.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hrs after removal of the patch

Score:

3.5

Max. score:

8

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Well-defined erythema with very slight or slight oedema was noted at all treated skin sites one hour after patch removal and at subsequent 24, 48 and 72-hr observations

Other effects:

Depilated glossy skin was noted at all treated skin sites and at all observations times and persisted to the 7 day observation time. Reduced re-growth of fur and desquamation were also noted at the 7 day observation period.

Interpretation of results:

Category 2 (irritant)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a GLP skin irritation study in rabbits, equivalent to guideline (OECD TG 404), undiluted diammonium hexachloropalladate produced moderate skin irritation.

Executive summary:

In a GLP skin irritation study in rabbits, equivalent to guideline (OECD TG 404), neat diammonium hexachloropalladate (0.5 g) was applied (semi-occluded) to the clipped, intact skin of three rabbits. After 4 hrs, the patches were removed and, approximately 1 hr later, the skin sites assessed for erythema (and eschar) formation and oedema formation. These sites were again assessed 24, 48 and 72 hrs, and 7 days later.

The sums of the 24- and 72-hr values were combined and divided by six to give a primary irritation score of 3.5 (of 8). Ammonium hexachloropalladate (IV) was therefore considered as a moderate skin irritant in this test system. No corrosive effects were noted. Although the skin irritation was reversible within the 7-day observation period, depilated glossy skin persisted for the 7 days, and desquamation and reduced re-growth of fur was also noted at 7 days. As such, it would be precautionary to classify 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:

4 September 1989 – 4 September 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to a company standard protocol designed to comply with the recommendations of OECD guideline No. 405

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, UK
- Age at study initiation: approx. 12-16 wk
- Weight at study initiation: 2.95 kg
- Housing: individually in a suspended metal cages
- Diet: ad libitum Rabbit Diet supplied by Preston Farmers Limited, New Leake, Boston, Lincolnshire, UK
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 61
- Air changes (per hr): approx. 15/hr
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approx. 100 mg

Duration of treatment / exposure:

1 hr

Observation period (in vivo):

1 hr

Number of animals or in vitro replicates:

One male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

SCORING SYSTEM: Eye damage/irritation was assessed 1 hr following treatment according to Draize, 1959 and the numerical values corresponding to each tissue were recorded to give the total score for the conjunctivae (redness, chemosis and discharge), iris and cornea (degree and area of opacity). Using the numerical data obtained, the ocular irritancy potential was assessed by a modified version of the system described by Kay and Calandra, 1962.

TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: 1 hr

Score:

<= 106

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 hr

Score:

80

Max. score:

80

Reversibility:

not specified

Remarks on result:

other: Total corneal opacity noted 1 hr after treatment.

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hr

Score:

<= 10

Reversibility:

not specified

Remarks on result:

other: Corneal opacity precluded evaluation of the iridial damage.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1 hr

Score:

<= 16

Reversibility:

not specified

Remarks on result:

other: Yellow-coloured staining of the nictitating and conjunctival membranes precluded evaluation of the conjunctival redness. Severe swelling of the conjunctival membranes was also noted.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hr

Score:

4

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

Severe ocular reactions were produced 1 hr after treatment. Total corneal opacity was noted 1 hr after treatment and this precluded evaluation of the iridial damage. Severe swelling of the conjunctival membranes was noted, however yellow-coloured staining of the nictitating and conjunctival membranes precluded evaluation of the conjunctival redness.

Other effects:

The animal showed signs of distress and was killed, for humane reasons, 1 hr after treatment.

Interpretation of results:

Category I

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a GLP eye irritation study, equivalent to OECD Test Guideline 405, undiluted diammonium hexachloropalladate (100 mg) produced very severe eye irritation following instillation into the eye of one male rabbit.

Executive summary:

In a GLP study, equivalent to OECD Test Guideline 405, undiluted diammonium hexachloropalladate (100 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. The treated eye was then assessed, after 1 hr, using the Draize scale for signs of irritation on the cornea, iris and conjunctiva.

Due to signs of distress, the animal was killed, for humane reasons, 1 hr after treatment and no further animals were tested. The scores were combined using a modified version of the system described by Kay and Calandra to give an ocular irritancy potential of ≤106. Diammonium hexachloropalladate was, therefore, considered a very severe irritant in this test system.

As the results were based on only one rabbit, it is not possible to give a definitive interpretation according to EU CLP criteria. However, it is considered appropriate to classify the test material for serious eye damage (Category 1), according to CLP criteria (EC 1272/2008), 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. 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,equivalent to OECD Test Guideline 405, neat diammonium hexachloropalladate (0.5 g) was applied (semi-occluded) to the clipped, intact skin of three rabbits. After 4 hrs, the patches were removed and, approximately 1 hr later, the skin sites assessed for erythema (and eschar) formation and oedema formation. These sites were again assessed 24, 48 and 72 hrs, and 7 days later. The sums of the 24- and 72-hr values were combined and divided by six to give a primary irritation score of 3.5 (out of a possible 8). Diammonium hexachloropalladate was therefore considered as a moderate skin irritant in this test system. No corrosive effects were noted. Although the skin irritation was reversible within the 7-day observation period, depilated glossy skin persisted for the 7 days, and desquamation and reduced re-growth of fur was also noted at 7 days (Guest, 1989a). As such, it would be precautionary to classify as a skin irritant (Category 2), according to CLP criteria (EC 1272/2008). In support, diammonium hexachloropalladate was strongly irritant in a limited, non-GLP, rabbit study (Campbell et al., 1975.

In a GLP study, equivalent to OECD Test Guideline 405, undiluted diammonium hexachloropalladate (100 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. The treated eye was then assessed, after 1 hr, using the Draize scale for signs of irritation on the cornea, iris and conjunctiva. Due to signs of distress, the animal was killed, for humane reasons, 1 hr after treatment and no further animals were tested. The scores were combined using a modified version of the system described by Kay and Calandra to give an ocular irritancy potential of ≤106. Diammonium hexachloropalladate was, therefore, considered a very severe irritant in this test system (Guest, 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 appropriate 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 its 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, similar to OECD guidelines. Both available studies indicate skin irritant effect.

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), diammonium hexachloropalladate should be classified as a skin irritant (category 2) and for eye damage (category 1), according to EU CLP criteria (EC 1272/2008).