Palladium dinitrate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 January 2003 to 13 March 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD, EU, EPA), to GLP, on the dihydrate, with minor deviations (humidity) that are not considered to affect the validity of the study.

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:

deviations form the minimum humidity level recommended, which were not considered to have affected the study integrity.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

yes

Remarks:

deviations form the minimum humidity level recommended, which were not considered to have affected the study integrity.

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

yes

Remarks:

deviations form the minimum humidity level recommended, which were not considered to have affected the study integrity.

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese MAFF

Deviations:

yes

Remarks:

deviations form the minimum humidity level recommended, which were not considered to have affected the study integrity.

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:

Palladium dinitrate dihydrate

IUPAC Name:

Palladium dinitrate dihydrate

Constituent 2

Reference substance name:

Palladium(II) nitrate dihydrate

Cas Number:

32916-07-7

Molecular formula:

2NO3.Pd.2H2O

IUPAC Name:

Palladium(II) nitrate dihydrate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Palladium(II)nitrate dihydrate
- Substance type: orange-brown powder
- Physical state: solid
- Analytical purity: 40.1% (+/- 0.1%) palladium
- Impurities (identity and concentrations): no data [but see gentox study, with same batch no]
- Purity test date: no data [see gentox study, with same batch no.]
- Lot/batch No.: 2403/02-02
- Expiration date of the lot/batch: 21 October 2003
- Stability under test conditions: no data
- Storage condition of test material: room temperature in dark
- Other: [Please note that the dihydrate has a different CAS RN (32916-07-7) to the anhydrous form (10102-05-3)]

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 5 weeks
- Weight at study initiation: 310-355 g
- Housing: 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

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

0.1% for injection and 2% epidermal application (induction)
2% for epidermal application (challenge)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

0.1% for injection and 2% epidermal application (induction)
2% for epidermal application (challenge)

No. of animals per dose:

10 in test group
5 in control group

Details on study design:

RANGE FINDING TESTS: three animals each injected with either 0.1 and 0.2%, or 0.5 and 1%, or 2 and 5%. Examined 24 and 48 hr later
b) two animals each dose conbination dosed topically with either 0.5 and 1%, or 2 and 5%. Assessed at 24 and 48 hr

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal injection followed by topical application to the injection site one week later. Three pairs of simultaneous injections were given as follows: Freunds complete adjuvant; 0.1% test substance; test substance emulsified in the adjuvant.
- Exposure period: 48 hr - dermal application
- 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: 0.1% for injection and 2% epidermal application

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 22
- Exposure period: 24 hr
- Test groups: 1 test and 1 control group
- Control group: treated in same way
- Site: flank
- Concentrations: 2%
- Evaluation (hr after challenge): 24 and 48 hr after removal of the dressing

OTHER:

Challenge controls:

Treated with 2%

Positive control substance(s):

no

Remarks:

Not as part of study but routine checked (last check October/November 2002)

Study design: in vivo (LLNA)

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

2%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No systemic toxicity

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 2%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No systemic toxicity.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

2%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No systemic toxicity

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No systemic toxicity.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

2%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No systemic toxicity

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 2%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No systemic toxicity.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

2%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No systemic toxicity

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 2%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No systemic toxicity.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Palladium dinitrate dihydrate failed to induce skin sensitisation in an OECD Test Guideline 406 GPMT, to GLP, in which a group of ten guinea pigs were dermally challenged with 2% of the test compound following a two stage induction with 0.1% by intradermal injection and 2% applied topically.

Executive summary:

The ability of palladium dinitrate dihydrate 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 females.

Animals were induced with 0.1% by intradermal injection, followed one week later by a second induction by topical application of 2% of the test substance under a 48 -hr occlusive patch. Control animals were similarly treated but without the test substance. A challenge dose of 2% was applied under an occlusive patch for 24 hr, three weeks after the start of induction to both test and control animals. These doses were selected after a preliminary range-finding study to determine irritation. Scoring of the treated areas was carried out 24 and 48 hr after removal of the patches.

No positive reactions were observed in the test or control animals on examination at 24 and 48 hr after removal of the challenge patches.

Overall, palladium dinitrate dihydrate was not a contact sensitiser in a reliable GPMT, andthus would not require classification as a skin sensitiser according to EU CLP criteria (EC 1272/2008).