Tetraamminepalladium(2+) diacetate

Skin sensitisation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

Tetraamminepalladium dichloride

IUPAC Name:

Tetraamminepalladium dichloride

Constituent 2

Reference substance name:

Tetraamminepalladium(2+) dichloride

EC Number:

237-489-7

EC Name:

Tetraamminepalladium(2+) dichloride

Cas Number:

13815-17-3

Molecular formula:

H8Cl2N4Pd

IUPAC Name:

Tetraamminepalladium(2+) dichloride

Details on test material:

- Name of test material (as cited in study report): tetraammine palladium chloride
- Substance type: pale yellow crystalline solid
- Physical state: solid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: DK0164
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: room temperature in dark

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

0.01% in distilled water - injection
10% in distilled water - topical induction
1% and 2% in distilled water - topical challenge

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

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

Results and discussion

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.

In vivo (non-LLNA)

Results

Results 1

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.

Results 2

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.

Results 3

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..

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:

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..

Any other information on results incl. tables

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).

Applicant's summary and conclusion

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).