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Description of key information

In two OECD Test Guideline 406 in vivo guinea pig maximisation tests (GPMTs), to GLP, both of the structurally related compounds (tetraamminepalladium dichloride and tetraamminepalladium hydrogen carbonate) induced skin sensitisation in at least 60% of the treated animals (Allen, 1997b, 2000).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

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Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15-16 June 2000
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD guideline study, to GLP, on closely-related surrogate
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study conducted in 2000
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited
Burton-on-Trent
Staffordshire
UK
- Age at study initiation:
- Weight at study initiation: 347-421 g
- Housing: solid-floor polypropylene cages; bedding - woodchips
- Diet (e.g. ad libitum): conventional; ad libitum
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
0.01% in distilled water - injection
10% in distilled water - topical induction
1% and 2% in distilled water - topical challenge
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
0.01% in distilled water - injection
10% in distilled water - topical induction
1% and 2% in distilled water - topical challenge
No. of animals per dose:
10 (5 animals in control group)
Details on study design:
RANGE FINDING TESTS:
Intradermal induction: one animal each treated with 0.01, 0.05, 0.1, 0.5, 1.0 or 5% and examined for erythema at 24, 48 and 72 hr and at 7 days

Topical induction: Two guinea pigs (injected with Freund’s complete adjuvant 14 days earlier) each received applications of 5, 10, 25 and 50% of the test material under an occlusive dressing. Examined for erythema and odema at 1, 24 and 48 hr.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: One injection, followed 7 days later by topical application
- Exposure period: topical – 48 hr

- Test groups: Injection – three injections in shoulder region on each side of the mid-line as follows:
a) Freund's Complete Adjuvant plus distilled water in the ratio 1:1
b) 0.01% w/w formulation of the test material in distilled water
c) 0.01% w/w formulation of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water.

- Control group: as above, but without the test material
- Site: shoulder region, on each side of the mid-line
- Frequency of applications: once
- Duration: topical – 48 hr
- Concentrations: 10%

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: 14 days after the topical induction
- Exposure period: 24 hr
- Test groups:
- Control group: treated with test substance as test group
- Site: flank
- Concentrations: 1% to left flank, 2% to right flank
- Evaluation (hr after challenge): 24 and 48 hr


Challenge controls:
Treated as for test group
Positive control substance(s):
no
Positive control results:
No positive controls included in this study. A table giving historical positive control data for 2-mercaptobenzothiazole is included in the study report, showing between a 70-100% incidence of sensitisation in groups of ten female guinea pigs.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2%
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
No evidence of adverse effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2%. No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: No evidence of adverse effects.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1%
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
No evidence of adverse effects
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 5.0. Total no. in groups: 10.0. Clinical observations: No evidence of adverse effects.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1 and 2%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
One animal was found dead on day 14 from causes not related to the test material. No other clinical signs were evident.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1 and 2%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: One animal was found dead on day 14 from causes not related to the test material. No other clinical signs were evident..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1 and 2%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
One animal was found dead on day 14 from causes not related to the test material. No other clinical signs were evident.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1 and 2%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: One animal was found dead on day 14 from causes not related to the test material. No other clinical signs were evident..

In test group with 2% challenge dose, at 48 hr 6 animals showed erythema (grades 1 and 2) and one animal had odema (at 24 hr the totals were 9 and 4, respectively for erythema and odema. Reactions that had disappeared by 48 hr were not attributed to sensitisation).

In test group with 1% challenge dose, at 48 hr 5 animals showed erythema (grade 1) and one animal had odema (at 24 hr the totals were 9 and 1, respectively for erythema and odema. Reactions that had disappeared by 48 hr were not attributed to sensitisation).

Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
In an OECD Guideline study, to GLP, tetraammine palladium dichloride exhibited moderate skin sensitising potential when tested in an in vivo guinea pig maximum study (GPMT).
Executive summary:

Tetraamminepalladium dichloride was assessed for its contact sensitising potential in a guinea pig maximum test (GPMT) conducted according to OECD Test Guideline 406, and to GLP.

A group of ten male animals were induced by intradermal injection of 0.1% of the test material (in distilled water), with and without Freund's Complete Adjuvant, followed 7 days later by topical exposure to 10% (in distilled water) under an occluded patch. Challenge doses of 1 and 2% (in distilled water) were applied to different sites 14 days later and the areas examined at 24 and 48 hr for erythema and oedema. A further group of five males were used as controls, receiving the same induction procedure but without the test substance, and challenged similarly to the treatment group.

Six of the ten treated animals showed evidence of sensitisation at 48 hr (erythema, grade 1 or 2); three further animals exhibited erythema at 24 hr but not at 48 hr and these reactions were therefore considered not to be due to sensitisation. Tetraamminepalladium chloride exhibited moderate skin sensitising potential in this study.

According to EU CLP criteria (EC 1272/2008), tetraamminepalladium dichloride should be classifed as a skin sensitiser (category 1A).

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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, on closely-related surrogate. However, any possible deviations could not be fully assessed as the study report appears to have some pages omitted. These pages may contain important information, including further details on exposure, use of an adjuvant, location and preparation of the test site (clipped/shaved?), controls, test animals and environmental conditions.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study conducted in 1997
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

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

IN-LIFE DATES: no data
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
0.01% intradermal induction, 5% topical induction, and 1 and 2% topical challenge
Route:
other: epicutaneous, but no further details in study report on whether occlusive or semi-occlusive
Vehicle:
arachis oil
Concentration / amount:
0.01% intradermal induction, 5% topical induction, and 1 and 2% topical challenge
No. of animals per dose:
Ten animals in total
Details on study design:
RANGE FINDING TESTS: A sighting test was carried out with six guinea pigs involving intradermal injections (induction phase) of the test material at varying concentrations between 0.05 and 5% in distilled water, a 48-hr topical (induction) application of the test material at concentrations between 0.05 and 75% (in arachis oil) in four guinea pigs, and a 24-hr topical (challenge) application at 0.5-5% (in arachis oil) in two guinea pigs.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: intradermal injection (no details in study report on numbers) and single patch test
- Exposure period: 48-hr patch test
- Test groups: ten animals in total
- Control group: five animals
- Site: no data
- Frequency of applications: single
- Concentrations: 0.01% intradermal induction and 5% topical induction

B. CHALLENGE EXPOSURE
- No. of exposures: Single patch tests
- Day(s) of challenge:
- Exposure period: 24-hr
- Test groups: ten animals in total
- Control group: five animals
- Site: no data
- Concentrations: 1 and 2% topical challenge
- Evaluation (hr after challenge): 24 and 48-hrs

OTHER: Bodyweights were measured on day 0 and day 24.
Challenge controls:
Topical challenge with the test material at a concentration of 1 and 2% in arachis oil
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1 and 2%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Erythema seen in all animals at challenge with 1 and 2%. Oedema seen in seven animals at 1% and all ten animals at 2% challenge.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1 and 2%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Erythema seen in all animals at challenge with 1 and 2%. Oedema seen in seven animals at 1% and all ten animals at 2% challenge..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1 and 2%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No erythema or oedema seen in any of the controls
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1 and 2%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No erythema or oedema seen in any of the controls.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1 and 2%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
Erythema recorded in all ten animals at both concentrations. Oedema was recorded in two animals at 1% and in four animals at 2%. Desquamation was also seen in two guinea pigs.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1 and 2%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Erythema recorded in all ten animals at both concentrations. Oedema was recorded in two animals at 1% and in four animals at 2%. Desquamation was also seen in two guinea pigs..
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1 and 2%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No erythema or oedema seen in any of the controls
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1 and 2%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No erythema or oedema seen in any of the controls.
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
In an OECD Guideline study, tetraamminepalladium hydrogen carbonate exhibited extreme skin sensitising potential when tested in an in vivo guinea pig maximum study (GPMT).
Executive summary:

Tetraamminepalladium hydrogen carbonate was assessed for its contact sensitising potential in a guinea pig maximum test (GPMT) conducted according to OECD Test Guideline 406. The test substance was administered to ten guinea pigs (induction phase) by intradermal injection (presumably in combination with Freunds Complete Adjuvant) at a concentration of 0.01% (in arachis oil) and topically (48-hr patch test) at 5% (again in arachis oil). A challenge (presumably 10-14 days after the induction phase) to the (presumably hairless and intact) skin of ten treated guinea-pigs and five control animals was applied (24-hr patch test) at a concentration of 1 and 2% in arachis oil. The skin was observed 24- and 48-hr after patch removal for erythema, oedema and other skin reactions.

 

Erythema was seen in all treated animals 24- and 48-hr after challenge with 1 and 2% of the test material. Oedema was seen in seven of the treated animals at 1% and in all ten treated animals at 2%, 24-hrs after removal of the challenge patch tests. The number of animals with oedema was reduced to two and four, 48-hrs after removal of the 1 and 2% challenge patch tests, respectively. Desquamation was also seen in two guinea pigs. All animals gained weight over the study period, and body weight gains from day 0 to day 24 appeared comparable between the treated and control groups. In summary, a maximisation test involving a topical challenge application of tetrammine palladium hydrogen carbonate at a concentration of 1 and 2% to the skin of ten guinea pigs produced sensitisation reactions in all animals; a 100% (10/10) sensitisation rate. No reactions were recorded on the skin of five control animals. The test material was therefore considered as an extreme sensitiser to guinea pig skin, and classified as a sensitiser according to EU labelling regulations.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

No relevant human sensitisation data were identified. No in vitro skin sensitisation studies were identified, or are required, as reliable in vivo studies are already available.

 

Tetraamminepalladium dichloride was assessed for its contact sensitising potential in a guinea pig maximum test (GPMT) conducted according to OECD Test Guideline 406, and to GLP. A group of ten male animals were induced by intradermal injection of 0.1% of the test material (in distilled water), with and without Freund's Complete Adjuvant, followed 7 days later by topical exposure to 10% (in distilled water) under an occluded patch. Challenge doses of 1 and 2% (in distilled water) were applied to different sites 14 days later and the areas examined at 24 and 48 hr for erythema and oedema. A further group of five males were used as controls, receiving the same induction procedure but without the test substance, and challenged similarly to the treatment group. Six of the ten treated animals showed evidence of sensitisation at 48 hr (erythema, grade 1 or 2); three further animals exhibited erythema at 24 hr but not at 48 hr and these reactions were therefore considered not to be due to sensitisation. Tetraamminepalladium dichloride exhibited moderate skin sensitising potential in this study (Allen, 2000).

 

In another OECD Guideline GPMT, tetraamminepalladium hydrogen carbonate was assessed for its contact sensitising potential. The test substance was administered to ten guinea pigs (induction phase) by intradermal injection (presumably in combination with Freund’s Complete Adjuvant) at a concentration of 0.01% (in arachis oil) and topically (48-hr patch test) at 5% (again in arachis oil). A challenge (presumably 10-14 days after the induction phase) to the (presumably hairless and intact) skin of ten treated guinea-pigs and five control animals was applied (24-hr patch test) at a concentration of 1 and 2% in arachis oil. The skin was observed 24- and 48-hr after patch removal for erythema, oedema and other skin reactions. Erythema was seen in all treated animals 24 and 48 hr after challenge with 1 and 2% of the test material. Oedema was seen in seven of the treated animals at 1% and in all ten treated animals at 2%, 24 hr after removal of the challenge patch tests. The number of animals with oedema was reduced to two and four, 48 hr after removal of the 1 and 2% challenge patch tests, respectively. Desquamation was also seen in two guinea pigs. All animals gained weight over the study period, and body weight gains from day 0 to day 24 appeared comparable between the treated and control groups. In summary, a GPMT involving a topical challenge application of tetraamminepalladium hydrogen carbonate at a concentration of 1 and 2% to the skin of ten guinea pigs produced sensitisation reactions in all animals; a 100% (10/10) sensitisation rate. No reactions were recorded on the skin of five control animals (Allen, 1997b).

Tetraamminepalladium dichloride and hydrogen carbonate are considered to fall within the scope of the read-across category "tetraamminepalladium salts". See IUCLID section 13 for full read-across justification report.

 


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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No respiratory tract sensitisation data are available. A new study was not conducted as no standard and validated test method is available and it is not a REACH Standard Information Requirement.

Justification for classification or non-classification

Based on the results of the available and reliable GPMTs on structurally-related compounds, tetraamminepalladium diacetate should be classified as a (strong) skin sensitiser (category 1A) according to EU CLP criteria (EC 1272/2008).