Palladium (II) di(4-oxopent-2-en-2-oate)

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 July to 26 August 2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Preliminary tests for a guideline LLNA study performed to GLP. The main study was not performed on the basis of animal welfare, given that the test substance appeared to be a strong sensitiser in these preliminary tests. Humidity slightly exceeded the upper limit recommended by the guideline (77% vs 70%), as did test animal age (13 weeks, not 8-12 weeks, in one preliminary study).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

yes

Remarks:

Humidity slightly exceeded the upper limit recommended by the guideline (77% vs 70%), as did test animal age (13 weeks, not 8-12 weeks, in one preliminary study). These deviations are considered to have no impact on the results and integrity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Palladium di(4-oxopent-2-en-2-oate)

IUPAC Name:

Palladium di(4-oxopent-2-en-2-oate)

Constituent 2

Reference substance name:

Palladium (II) di(4-oxopent-2-en-2-oate)

EC Number:

237-859-8

EC Name:

Palladium (II) di(4-oxopent-2-en-2-oate)

Cas Number:

14024-61-4

Molecular formula:

C10H14O4Pd

IUPAC Name:

Palladium (II) di(4-oxopent-2-en-2-oate)

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): Palladium (II) di(4-oxopent-2-en-2-oate)
- Substance type: No data
- Physical state: Yellow solid
- Analytical purity: "100%"
- Impurities (identity and concentrations) (ppm): platinum (40), rhodium (6), iridium, antimony and silicon (<10 each), manganese and tin (<5 each), ruthenium, gold, silver, aluminium, cobalt, copper, iron, magnesium, lead and zinc (<2 each), calcium, chromium and nickel (<1 each)
- Composition of test material, percentage of components: Palladium at 34.98%
- Purity test date: 29 May 2013
- Lot/batch No.: 21613
- Expiration date of the lot/batch: June 2014
- Stability under test conditions: No data
- Storage condition of test material: Room temperature, under inert gas, protected from heat and light

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: 13 weeks in preliminary test 2 (no further data)
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): 31-77% during acclimation period (no further data)
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: No data

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

Preliminary test 1: 10 or 25% (w/v)
Preliminary test 2: 2.5 or 5% (w/v)
Preliminary test 3: 0.5 or 1% (w/v)

No. of animals per dose:

2

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: Tested in a range of solvents (N,N-dimethylformamide, methyl ethyl ketone, propylene glycol, dimethyl sulfoxide and Pluronic). Acetone/olive oil (AOO) was considered the best vehicle "taking into account the test item characteristics, its usage and requirements of the relevant OECD guideline". The highest achievable concentration was 25% (w/v).
- Irritation: Three preliminary tests were conducted (described throughout this IUCLID record; the "main" study was not conducted).
- Lymph node proliferation response: No data.

MAIN STUDY - Not conducted due to responses indicative of a strong sensitiser seen in the preliminary tests.

TREATMENT PREPARATION AND ADMINISTRATION: No data.

Positive control substance(s):

other: Not required for preliminary study.

Statistics:

Not required for preliminary study.

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: Not calculated (main study not performed).

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Not calculated (main study not performed).

Any other information on results incl. tables

No evidence of erythema was seen in any animal. No mortality was observed. Marked body weight loss (of more than 5%) was seen in one animal treated with 25%, and both of the animals in the groups treated with 2.5, 5 and 10%. Clinical signs of toxicity included a hunched back in the groups treated with 10 or 25%. Alopecia was observed in the 0.5, 1, 2.5 and 5% dose groups. Scale was seen in the 1, 2.5 and 5% groups.

Increased ear thickness (>25%) was seen in all dose groups. Ear punch weights were outside the historical control range in the 2.5, 5, 10 and 25% dose groups.

The lymph nodes were larger than normal (subjectively) in all dose groups.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

In preliminary studies conducted prior to a planned guideline local lymph node assay, performed to GLP, effects observed after treatment with palladium (II) di(4-oxopent-2-en-2-oate) were consistent with those of a strong skin sensitiser. The main study was not conducted, based on animal welfare considerations.

Executive summary:

It was planned that the skin sensitising potential of palladium di(4-oxopent-2-en-2-oate) should be assessed in a mouse local lymph node assay (LLNA), performed in accordance with OECD Test Guideline 429, and to GLP. Preliminary irritation/toxicity studies were first conducted on groups of 2 female CBA/J Rj mice.

 

Initially, the test substance at 10 or 25% (in acetone: olive oil, 4:1) was applied dermally to mice. However, increased ear thickness was observed, without any visible erythema. Preliminary tests were subsequently performed on mice treated with 2.5 or 5%, and then on groups treated with 0.5 or 1%. Increased ear thickness was seen, without erythema, in all dose groups. Ear punch weight was above the historical control range in all but the lowest of the dose groups. The draining lymph nodes were also considered subjectively to be larger than normal in all dose groups.

 

As the dilution of irritant materials “will usually reduce the ear swelling to acceptable levels”, and no erythema was observed, the study investigator concluded that the observed results were indicative of sensitisation rather than irritation. For reasons of animal welfare, further animal use was therefore not considered justified, and the full LLNA was not performed.

 

It was concluded, based on the results of the preliminary irritation/toxicity studies, that palladium di(4-oxopent-2-en-2-oate) showed signs (notably increased ear thickness at all doses, without visible erythema, and enlarged lymph nodes) consistent with a strong sensitiser.