Tetraamminepalladium(2+) dichloride

Endpoint summary

Description of key information

In an OECD guideline study, no irritation potential was observed when tetraamminepalladium dichloride was applied (under occlusion for 4 hr) to the intact shaved skin of three rabbits (Driscoll, 1981).

In an OECD Guideline study, to GLP, instillation of undiluted tetraamminepalladium dichloride to one eye of each of three rabbits (without subsequent washing) caused moderate to severe irritation, and severe irritation in three rabbits when the eye was rinsed after 30 seconds (Driscoll and Collier, 1981).

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:

18 to 21 November 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Remarks:

individual experimental studies were not inspected for GLP compliance. Inspections of skin irritation studies were reported to be carried out 19-20 February 1981

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Nottingham University
School of Agriculture
Sutton Bonington
Leicestershire
UK
- Age at study initiation: no data
- Weight at study initiation: 2.34-3.19 kg
- Housing: Individually in suspended metal cages
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): no data
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

other: no concurrent control site

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg moistened with water to make a paste


VEHICLE
no data

Duration of treatment / exposure:

4 hr

Observation period:

72 hr with an additional 7 day observation period if irritation was still apparent at 72 hr

Number of animals:

Three

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: no data
- Type of wrap if used: absorbent lint covered with polythene, secured by adhesive tape. The trunk of each rabbit was wrapped in an elasticated bandage (Tubigrip)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton wool soaked in warm water
- Time after start of exposure: 4 hr

SCORING SYSTEM: assessed at 1, 24, 48 and 72 hr. Scored using the method of Draize (1959) for erythema/eschar formation and edema at all time points and the total scores were divided by 12 to hive the primary irritation index.
Primary irritation index Classification
0 non-irritant
> 0-2 mild irritant
> 2-5 moderate irritant
> 5-8 severe irritant

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: Mean of 1, 24, 48 and 72 hr time points

Score:

0

Max. score:

8

Reversibility:

other: no irritation observed

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: Mean of 1, 24, 48 and 72 hr time points

Score:

0

Max. score:

8

Reversibility:

other: no irritation observed

Irritation parameter:

edema score

Basis:

mean

Time point:

other: Mean of 1, 24, 48 and 72 hr time points

Score:

0

Max. score:

8

Reversibility:

other: no irritation observed

Irritant / corrosive response data:

None seen at any time point

Other effects:

No indication of whether systemic effects were assessed

Very slight yellowing staining of the test site which did not interfere with the assessment of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

In a guideline study, no irritation potential was observed when tetraammine palladous chloride was applied (under occlusion for 4 hr) to the intact shaved skin of three rabbits.

Executive summary:

In an OECD Test Guideline 404 study, tetraammine palladous chloride (0.5 g, moistened) was applied (occluded) to the clipped but intact skin of three New Zealand white rabbits. After 4 hours, the dressings were removed and the skin sites assessed for signs of irritation (oedema and erythema/eschar) and corrosion at 1, 24, 48 and 72 hours.

No irritation (erythema/eschar formation or erythema) or corrosion of the skin was seen at any time point during the 72 hr study period. The primary irrational index was therefore 0, and tetraammine palladous chloride is classified as non-irritating.

No skin classification, according to EU CLP criteria (EC 1272/2008), is required on the basis of this study.

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:

21 to 28 December 1981

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

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.36-3.16 kg
- Housing: metal cages
- Diet (e.g. ad libitum): conventional; ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): no data
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: yes, concurrent no treatment; other eye served as control

Amount / concentration applied:

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

Duration of treatment / exposure:

After 30 seconds (“with rinsing” group) or throughout observation period ("without rinsing” group)

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 in the “without rinsing” group; 3 in the “with rinsing” group

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes in one group
- Time after start of exposure: 30 seconds with 100 ml sterile distilled water at 37oC (one group)

SCORING SYSTEM: According to the numerical evaluation of Draize. For each tissue the total score was calculated as follows:
Total score for conjunctivae = (redness + chemosis + discharge) x 2
Total score for iris = any changes x 5
Total score for cornea = (degree of opacity x area of opacity) x 5

TOOL USED TO ASSESS SCORE: no data

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hr, and 7 days

Score:

27

Reversibility:

not fully reversible within: 7 days in two of the three animals

Irritation parameter:

overall irritation score

Remarks:

with rinsing

Basis:

mean

Time point:

other: 1, 24, 48 and 72 hr, and 7 days

Score:

31

Reversibility:

not fully reversible within: 7 days in two of the rabbits

Irritant / corrosive response data:

Without washing: One hour after treatment irritation showed as iridial congestion, conjunctival reness and severe chemosis. By seven days post treatment minimal chemosis was present in one animal and minimal chemosis and redness in another.

With washing: One hour following treatment irritation was exhibited as slight corneal opacity and iridial congestion in two rabbits, and slight to moderate conjunctival redness and moderate to severe chemosis in all three animals, which had not improved by 72 hours. By day 7 significant irritation was still persistent in the cornea and conjunctivae of two rabbits.

Other effects:

There is no indication that clinical signs of systemic toxic effects were evident.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

In an OECD Guideline study, to GLP, instillation of undiluted tetraammine palladous chloride to one eye of each of three rabbits without washing caused moderate to severe irritation and severe irritation in three rabbits when the eye was rinsed after 30 seconds

Executive summary:

In an OECD Guideline study, to GLP, undiluted tetraammine palladous chloride (100 mg, powdered) was instilled into the right eye of each of six New Zealand. The contralateral eye remained untreated and was used for control purposes. In half of the animals, the eyes were rinsed after 30 seconds with 100 ml of sterile distilled water.

Moderate to severe irritation was observed in the ‘non-rinsed group’, which (although had reduced in severity) was not fully reversible in two of the 3 rabbits within seven days after treatment. When the eyes were rinsed after a 30 second exposure, the test substance caused severe eye irritation in all three rabbits which (although had reduced in severity) still persisted at day 7 in two of the animals. No clinical signs of systemic toxic effects were reported.

Overall, tetraammine palladous chloride caused severe irritation to the eye of rabbits observed for a seven day period. Classification as an eye irritant (category 2), is required on the basis of the findings of this study and according to EU CLP criteria (EC 1272/2008).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No relevant irritation/corrosion human 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 an OECD Test Guideline 404 study, neat tetraamminepalladium dichloride (0.5 g, moistened) was applied (occluded) to the clipped but intact skin of three New Zealand white rabbits. After 4 hours, the dressings were removed and the skin sites assessed for signs of irritation (oedema and erythema/eschar) and corrosion at 1, 24, 48 and 72 hours. No irritation (erythema/eschar formation or erythema) or corrosion of the skin was seen at any time point during the 72-hr study period. The primary irrational index was therefore 0, and tetraamminepalladium dichloride is classified as non-irritating (Driscoll, 1981). No skin classification, according to EU CLP criteria (EC 1272/2008), is required on the basis of this study.

 

In an OECD Guideline study, to GLP, undiluted tetraamminepalladium dichloride (100 mg, powdered) was instilled into the right eye of each of six New Zealand rabbits. The contralateral eye remained untreated and was used for control purposes. In half of the animals, the eyes were rinsed after 30 seconds with 100 ml of sterile distilled water. Moderate to severe irritation was observed in the ‘non-rinsed group’, which (although had reduced in severity) was not fully reversible in two of the 3 rabbits within seven days after treatment. When the eyes were rinsed after a 30-second exposure, the test substance caused severe eye irritation in all three rabbits which (although reduced in severity) still persisted at day 7 in two of the animals. No clinical signs of systemic toxic effects were reported. Tetraamminepalladium dichloride caused severe irritation to the eye of rabbits observed for a 7-day period (Driscoll and Collier, 1981). Classification of tetraamminepalladium dichloride as an eye irritant (category 2), is required on the basis of the findings of this study and 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, and the only skin irritation study available.

Justification for selection of eye irritation endpoint:
GLP study, conducted to OECD guidelines, and the only eye irritation study available.

Justification for classification or non-classification

Based on the results of the available reliable skin and eye irritation studies (in rabbits), tetraamminepalladium dichloride need not be classified for skin irritation, but should be classified as an eye irritant (category 2), according to EU CLP criteria (EC 1272/2008).