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Diss Factsheets

Administrative data

Description of key information

In a guideline study (OECD TG 404), no irritation potential was observed when 0.5 g of tetraamminepalladium(II) hydrogen carbonate, moistened in water, was applied (semi-occluded for 4 hr) to the intact shaved skin of three rabbits (Allen, 1995b).

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 a guideline study (OECD TG 405), to GLP, undiluted tetraamminepalladium hydrogen carbonate (0.1 mL; 91 mg) produced severe eye irritation following instillation into the eye of one rabbit. The animal was killed at 24 hours for humane reasons (Allen, 1995c).

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).

 

No relevant respiratory tract irritation data were identified.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin 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: see 'Remark'
Remarks:
OECD guideline study to GLP. Limited reporting (e.g. test purity and exposure area)
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sanbach, Cheshire, UK.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.6 and 2.71 kg (females) and 2.69 kg (male)
- Fasting period before study: no data
- Housing: individually housed in suspened metal cages
- Diet (e.g. ad libitum): ab libitum
- Water (e.g. ad libitum): ab libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-19
- Humidity (%): 49-56
- Air changes (per hr): about 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: no data
Type of coverage:
semiocclusive
Preparation of test site:
other: intact
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 of distilled water)

Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 (2 females and 1 male)
Details on study design:
TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: cotton gauze patch (2.5 x 2.5 cm)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing. Residual test material removed by gentle swabbing with cotton wool soaked in 74% industrial methylated spirits.

SCORING SYSTEM: Individual scores for erythema/eschar and oedema were made for the three rabbits according to the Draize classification scheme at the 1, 24, 48 and 72-hr readings. The mean of the scores at the 24 and 72-hr observations were summed, and divided by 6 to give the primary irritation index.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1, 24, 48 and 72-hour observations
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
female 1
Time point:
24/48/72 h
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
female 2
Time point:
24/48/72 h
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
male
Time point:
24/48/72 h
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
female 1
Time point:
24/48/72 h
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
female 2
Time point:
24/48/72 h
Score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
male
Time point:
24/48/72 h
Score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
No irritation or corrosive effects seen during the study.
Other effects:
Yellow-staining was noted at all treated sites at 1, 24, 48 and 72-hr observations.
Interpretation of results:
GHS criteria not met
Conclusions:
In an OECD guideline study, to GLP, no irritation was observed when 0.5 g of tetraamminepalladium(II) hydrogen carbonate, moistened in water, was applied (semi-occluded for 4 hr) to the intact shaved skin of three New Zealand white rabbits.
Executive summary:

In an OECD Test Guideline 404 study, to GLP, 0.5 g of tetraamminepalladium(II) hydrogen carbonate, moistened with 0.5 mL of distilled water, was applied (semi-occluded) to the 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.

 

Yellow-staining was noted at all treated skin sites at 1, 24, 48 and 72 hrs. No irritation (erythema/eschar formation or erythema) or corrosion of the skin was seen at any time point during the study period. The primary irritation index was therefore 0, and tetraamminepalladium(II) hydrogen carbonate was classified as non-irritating.

 

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

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:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
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:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
18 to 21 November 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Within the category of tetraamminepalladium(II) compounds, data on three tetraamminepalladium(II) salts, the acetate, chloride, and hydrogen carbonate salts will be used to fill data gaps. Tetraamminepalladium(II) diacetate, dinitrate, dihydroxide, dichloride and di(hydrogencarbonate) are the target substances within the group. In all substances covered, the palladium is in the 2+ oxidation state, co-ordinated to four neutral ammonia molecules (giving an overall 2+ charge on the complex). Thus, the difference in anion (acetate, nitrate, hydroxide, chloride or hydrogen carbonate) represents the only structural difference between the compounds in this group. As detailed in the read-across justification report (cfr IUCLID section 13), all the human health toxicity data included in the category member dossiers should be considered equally applicable to each of the category member substances.
Reason / purpose for cross-reference:
read-across source
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:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
other: not applicable
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

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15-16 March 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study, to GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: 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., Motson, Sandbach, Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.60 kg
- Housing: Individually housed in a suspended metal cage
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-19 deg C
- Humidity (%): 49-50%
- Air changes (per hr): 15/hour
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 15 March 1995 To: 16 March 1995
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye acted as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (equivalent to 91 mg)
- Concentration (if solution): Not applicable

VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
24 hours [animal was killed for humane reasons after 24 hours due to signs of pain and discomfort]
Number of animals or in vitro replicates:
One
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not done
- Time after start of exposure: Not applicable

SCORING SYSTEM: Modified Kay and Calandra classification system

TOOL USED TO ASSESS SCORE: No data
Irritation parameter:
overall irritation score
Basis:
animal #1
Remarks:
single animal tested
Time point:
other: 1 hour
Score:
53
Max. score:
110
Reversibility:
other:
Remarks on result:
other: animal killed at 24 hr for humane reasons
Irritation parameter:
overall irritation score
Basis:
animal #1
Remarks:
single animal tested
Time point:
24 h
Score:
81
Max. score:
110
Reversibility:
other:
Remarks on result:
other: animal killed at 24 hr for humane reasons
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
single animal tested
Time point:
other: 1 hour
Score:
40
Max. score:
80
Reversibility:
other:
Remarks on result:
other: animal killed at 24 hr for humane reasons
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
single animal tested
Time point:
24 h
Score:
60
Max. score:
80
Reversibility:
other:
Remarks on result:
other: animal killed at 24 hr for humane reasons
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
single animal tested
Time point:
other: 1 hour
Score:
5
Max. score:
10
Reversibility:
other:
Remarks on result:
other: animal killed at 24 hr for humane reasons
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
single animal tested
Time point:
24 h
Score:
5
Max. score:
10
Reversibility:
other:
Remarks on result:
other: animal killed at 24 hr for humane reasons
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
single animal tested
Time point:
other: 1 hour
Score:
8
Max. score:
20
Reversibility:
other:
Remarks on result:
other: animal killed at 24 hr for humane reasons
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
single animal tested
Time point:
24 h
Score:
16
Max. score:
20
Reversibility:
other:
Remarks on result:
other: animal killed at 24 hr for humane reasons
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
single animal tested
Time point:
other: 1 h
Score:
2
Reversibility:
other:
Remarks on result:
other: animal killed at 24 hr for humane reasons
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
single animal tested
Time point:
24 h
Score:
3
Reversibility:
other:
Remarks on result:
other: animal killed at 24 hr for humane reasons
Irritant / corrosive response data:
Translucent corneal opacity was noted at the 1-hour observation with opalescent corneal opacity at the 24-hour observation.
Iridial inflammation was noted at the 1 and 24-hour observations.
Moderate conjunctival irritation was noted at the 1-hour observation with severe conjunctival irritation at the 24-hour observation.
The nictitating and conjunctival membranes were pale in appearance with petechial haemorrhage of the nictitating membrane at the 1 and 24-hour observations.

Due to signs of pain and discomfort the animal was killed after 24-hour observation for humane reasons.
Other effects:
Residual test material was noted in the treated eye 1 and 24 hours after treatment.
 Irritation Parameter   

 Time after treatment   
 1 hour  24 hours
 Cornea    
 Degree of opacity  2  3
 Area of opacity  4  4
 Score  40  60
 Iris  1  1
 Score  5  5
 Conjunctivae    
 Redness  2  2
 Chemosis  2  3
 Discharge  0  3
 Score  8  16
 Total score  53  81
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In a guideline study, to GLP, undiluted tetraamminepalladium(II) hydrogen carbonate (0.1 mL; 91 mg) produced very severe eye irritation following instillation into the eye of one rabbit. The animal was killed at 24 hours for humane reasons.
Executive summary:

In an OECD guideline study (TG 405), conducted according to GLP, undiluted tetraamminepalladium(II) hydrogen carbonate (0.1 mL; 91 mg), was instilled into one eye of a single New Zealand white rabbit. The other eye remained untreated and acted as the control.

 

The treated eye was assessed, after 1 and 24 hours, using a modified Kay and Calandra classification system for signs of irritation on the cornea, iris and conjunctiva.

 

Tetraamminepalladium(II) hydrogen carbonate produced a maximum group mean score of 81.0 [maximum total score possible = 110] at 24 hours. The animal was killed at 24 hours for humane reasons and no further animals were tested.

 

The substance 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 (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:
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
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within:
Irritation parameter:
iris score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48 h
Score:
1
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
2
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible
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:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
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 an OECD Test Guideline 404 study, to GLP, 0.5 g of tetraamminepalladium(II) hydrogen carbonate, moistened with 0.5 mL of distilled water, was applied (semi-occluded) to the 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. Yellow-staining was noted at all treated skin sites at 1, 24, 48 and 72 hrs. No irritation (erythema/eschar formation or erythema) or corrosion of the skin was seen at any time point during the study period. The primary irritation index was therefore 0, and tetraamminepalladium(II) hydrogen carbonate was classified as non-irritating (Allen, 1995b).

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 (TG 405), conducted according to GLP, undiluted tetraamminepalladium(II) hydrogen carbonate (0.1 mL; 91 mg), was instilled into one eye of a single New Zealand white rabbit. The other eye remained untreated and acted as the control. The treated eye was assessed, after 1 and 24 hours, using a modified Kay and Calandra classification system for signs of irritation on the cornea, iris and conjunctiva. Tetraamminepalladium(II) hydrogen carbonate produced a maximum group mean score of 81.0 [maximum total score possible = 110] at 24 hours. The animal was killed at 24 hours for humane reasons and no further animals were tested. The substance was, therefore, considered a severe irritant in this test system (Allen, 1995c).

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 irritation data were identified. A new study was not conducted as it is not a REACH Standard Information Requirement.

Justification for classification or non-classification

Based on the results of the available skin irritation studies (in rabbits), tetraamminepalladium(II) hydrogen carbonate does not require classification as a skin irritant. 

Regarding eye irritation, as the results of the test with tetraamminapalladium(II) hydrogen carbonate were based on only one rabbit, it is not possible to give a definitive classification 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.