Dihydrogen tetrachloropalladate(2-)

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 November 2002 to 3 January 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD,EU, EPA, Japan), to GLP,

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

Dressings on 8 animals were removed early by mistake, test substance reapplied within 1 hr and exposure continued. Scoring of edema not written down

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

yes

Remarks:

Dressings on 8 animals were removed early by mistake, test substance reapplied within 1 hr and exposure continued. Scoring of edema not written down

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study conducted in 2003

Test material

Test material information

Constituent 1

Reference substance name:

Dihydrogen tetrachloropalladate(2-)

EC Number:

241-047-9

EC Name:

Dihydrogen tetrachloropalladate(2-)

Cas Number:

16970-55-1

Molecular formula:

Cl4Pd.2H

IUPAC Name:

dihydrogen tetrachloropalladate(2-)

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): dihydrogen tetrachloropalladate(II)
- Substance type: brown liquid
- Physical state: liquid
- Analytical purity: 99.95%
- Impurities (identity and concentrations): 0.05%
- Composition of test material, percentage of components: 47% by weight of dihydrogen tetrachloropalladate(II) in solution
- Purity test date: no data
- Lot/batch No.: 4515932529
- Expiration date of the lot/batch: 12 September 2003
- Stability under test conditions: at least 96 hr (in water)
- Storage condition of test material: room temperature, in dark
- Other:

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland
Kisslegg
Germany
- Age at study initiation: about 4 weeks
- Weight at study initiation: 361-393 g
- Housing: caged on purified sawdust
- 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): 21 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

0.05% and 0.1% for injection and 5% epidermal application (induction)
5% for epidermal application (challenge)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

0.05% and 0.1% for injection and 5% epidermal application (induction)
5% for epidermal application (challenge)

No. of animals per dose:

10 (test substance)
5 (controls)

Details on study design:

RANGE FINDING TESTS:
a) one animal each injected with either 0.1 and 0.2%, or 0.02 and 0.5%, or 0.5 and 1%, or 2 and 5%. Examined 24 and 48 hr later
b) two animals each dosed topically with either 0.5 and 1%, or 2 and 5%, or 10 and 20%. Assessed at 24 and 48 hr

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal followed by topical application to the injection site one week later. Three pairs of simultaneous injections were given as follows: Freunds complete adjuvant; 0.05% test substance; 0.1% test substance emulsified in the adjuvant.

- Exposure period: 48 hr
- Test groups: 1 test and 1 control group
- Control group: treated in same way but without the test substance
- Site: scapular region, each side of the midline
- Frequency of applications: once
- Duration: 21 days
- Concentrations: 0.05% and 0.1% for injection and 5% epidermal application

B. CHALLENGE EXPOSURE
- No. of exposures: 1

- Day(s) of challenge: Day 21
- Exposure period: 24 hr
- Test groups: 1 test and 1 control group
- Control group: treated in same way
- Site: flank
- Concentrations: 5%
- Evaluation (hr after challenge): 24 and 48 hr after removal of the dressing

OTHER:

Challenge controls:

5%

Positive control substance(s):

not required

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5%

No. with + reactions:

2

Total no. in group:

9

Clinical observations:

body weight gains normal

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5%. No with. + reactions: 2.0. Total no. in groups: 9.0. Clinical observations: body weight gains normal.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5%

No. with + reactions:

3

Total no. in group:

9

Clinical observations:

body weight gains normal

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5%. No with. + reactions: 3.0. Total no. in groups: 9.0. Clinical observations: body weight gains normal.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Any other information on results incl. tables

Brown/orange staining was observed at the treated sites after challange, but this evidently did not hamper scoring of the reactions.

One animal died on the day of first induction treatment. No further mortality was reported and no systemic toxicity was observed in the surviving animals.

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

Dihydrogen tetrachloropalladate(II) induced skin sensitisation in a OECD guideline GPMT, in which a group of ten guinea pigs were dermally challenged with 5% of the test compound following a two stage induction with 0.05% by intradermal injection and 5% applied topically.

Executive summary:

The ability of dihydrogen tetrachloropalladate to induce contact sensitisation was assessed in a OECD Test Guideline 406 guinea pig maximisation test (GPMT), conducted to GLP, using groups of 10 test and 5 control animals.

 

Animals were induced with 0.05% by intradermal injection, followed one week later by a second induction by topical application of 5% of the test substance under a 48-hr occlusive patch. Control animals were similarly treated but without the test substance. A challenge dose of 5% was applied under an occlusive patch for 24 hr three weeks after topical induction to both test and control animals. These doses were selected after a preliminary range-finding study.

 

Positive reactions were seen in 3 of the 9 animals exposed to the test substance after exposure to the challenge dose. One animal died on the day of first induction from abdominal bleeding. No reactions were observed in the control animals when examined at 24 and 48 hr after exposure to the challenge dose. No systemic toxicity was evident.

 

Overall, dihydrogen tetrachloropalladate induced skin sensitisation in 3 of 9 animals in the GPMT, thus requires classification as a skin sensitiser according to EU CLP criteria (EC 1272/2008).