tetraammine palladium (II) hydrogen carbonate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study performed between 21 February and 27 March 1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

OECD guidleine study, to GLP, conducted prior to the LLNA. No reporting of test purity and stability.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

not specified

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study conducted in 1997

Test material

Test material information

Constituent 1

Reference substance name:

Tetraamminepalladium (II) hydrogen carbonate

IUPAC Name:

Tetraamminepalladium (II) hydrogen carbonate

Constituent 2

Reference substance name:

134620-00-1

Cas Number:

134620-00-1

IUPAC Name:

134620-00-1

Details on test material:

- Name of test material (as cited in study report): Tetrammine palladium hydrogen carbonate
- Substance type: no data
- Physical state: no data
- Analytical purity: no data
- Lot/batch No.: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Specific details on test material used for the study:

TEST MATERIAL
- Physical state: Pale yellow powder
- Source and lot/batch No.of test material: DD0274
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: no data

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Ltd, Staffordshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 374-425 g
- Fasting period before study: no data
- Housing: singly or in pairs in solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 49-68
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: no data

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

arachis oil

Concentration / amount:

0.01% intradermal induction (with and without Freund's Complete Adjuvant (FCA)), 5% topical induction, and 1 and 2% topical challenge

Challenge

Route:

other: epicutaneous, but no further details in study report on whether occlusive or semi-occlusive

Vehicle:

arachis oil

Concentration / amount:

1 and 2% topical challenge

No. of animals per dose:

Ten test animals in total (and 5 controls)

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 0.01 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. The highest concentration producing only mild to moderate dermal irritaiton was selected for the topical induction stage of the main study and the highest non-irritant concentration and one lower were selected for the challange stage.

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 occlusive patch test
- Test groups: ten animals in total
- Control group: five animals
- Site: shoulder region, clippped
- Frequency of applications: a row of 3 injections (0.1 ml each) were made on each side of the mid-line. One week later, on the same clipped shoulder region, the occlusive patch-test was applied and held in place for 48 hr.
- Concentrations: 0.01% intradermal induction and 5% topical induction

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

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):

yes

Remarks:

hexylcinnameldehyde 85%, 2-mercaptobenzothiazole, ethyl 4-aminobenzoate 98%, 2,4-dinitrochlorobenzene

Results and discussion

In vivo (non-LLNA)

Results

Results 1

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.

Results 2

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.

Results 3

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..

Results 4

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.

Results 5

Group:

positive control

Remarks on result:

other: provided overview summary results of several positive control tests using known sensitizers demonstrate suitability of test system.

Remarks:

positive control materials: hexylcinnameldehyde 85%, 2-mercaptobenzothiazole, ethyl 4-aminobenzoate 98%, 2,4-dinitrochlorobenzene

Applicant's summary and conclusion

Interpretation of results:

Category 1A (indication of significant skin sensitising potential) based on GHS criteria

Conclusions:

In an in vivo guinea pig maximisation test (GPMT), conducted to GLP and according to OECD Test Guideline 406, tetraamminepalladium(II) hydrogen carbonate exhibited skin sensitising potential in all ten tested animals and was therefore classified as an extreme skin sensitiser.

Executive summary:

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

 

A group of ten animals were induced by intradermal injection (with and without Freunds Complete Adjuvant; FCA) at a concentration of 0.01% of the test material (in arachis oil) to the clipped shoulder region. One week later, at the same site, they recieved a occlusive 48 -hr patch-test at a concentration of 5% (again in arachis oil). Challenge doses of 1 and 2% (in arachis oil) were applied (occulsive patch test) 2 weeks later to the clipped flanks of treated animals and the areas examined 24 and 48 hr after patch removal for erythema, oedema and other skin reactions. A further group of five animals were used as controls, receiving the same induction procedure (involving vehicle and FCA) but without the test substance, and challenged similarly to the treatment group.

 

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 tetraamminepalladium(II) hydrogen carbonate at a concentration of 1 and 2% to the skin of guinea pigs produced sensitisation reactions in all ten animals; a 100% (10/10) sensitisation rate. No skin reactions were recorded oin the five controls. The test material exhibited extreme skin sensitising potential in this study.

 

According to EU CLP criteria (EC 1272/2008), tetraamminepalladium(II) hydrogen carbonate should be classified as a skin sensitiser (category 1A).