Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study conducted in 2000

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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)

Inductionopen allclose all
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
Challengeopen allclose all
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

Study design: in vivo (LLNA)

Statistics:
none

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)

Resultsopen allclose all
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
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 group
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..

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:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an OECD Guideline study, to GLP, tetraammine palladium dichloride exhibited moderate skin sensitising potential in an in vivo guinea pig maximisation test (GPMT).
Executive summary:

Tetraamminepalladium dichloride was assessed for its contact sensitising potential in a guinea pig maximisation 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 classified as a skin sensitiser (category 1A).

 

Tetraamminepalladium dichloride is closely related to tetraamminepalladium (II) nitrate and is considered a suitable surrogate for read-across for this endpoint. The proposed read-across is appropriate because it is expected that the target and source substances undergo biotransformation to a common product. In solution, the chloride and nitrate anions are expected to dissociate from the tetraamminepalladium cation; thus, this can be regarded as the common product and toxicologically-active species of both salts. The nitrate and chloride counterions would not have an impact on the overall sensitisation potential of the target or source substance, respectively. Therefore, it is considered that use of in vivo skin sensitisation data obtained in a test on tetraamminepalladium dichloride to fill a gap in the standard information requirements for tetraamminepalladium dinitrate is scientifically justified and suitably reliable.