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

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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).

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.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

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)

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

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.

Parameter:

SI

Remarks on result:

other: Not calculated (main study not performed).

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Not calculated (main study not performed).

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

No relevant human sensitisation data were identified.

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 (Váliczkó, 2014).

Migrated from Short description of key information:
Preliminary GLP studies were conducted prior to a planned OECD Test Guideline 429 mouse LLNA. Effects observed in the preliminary study were consistent with those of a strong sensitiser. The main study was not conducted, based on animal welfare considerations (Váliczkó, 2014).

Justification for selection of skin sensitisation endpoint:
Good quality preliminary study, to GLP, and the only skin sensitising study available.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

No respiratory tract sensitisation data are available. A new study was not conducted as no standard and validated test method is available and it is not a REACH Standard Information Requirement. Further, the compound is not expected to reach the lungs in appreciable quantities (based on respiratory tract deposition modelling data). Thus, inhalation will not be a significant route of exposure.

Migrated from Short description of key information:
No respiratory tract sensitisation data are available.

Justification for classification or non-classification

Palladium di(4-oxopent-2-en-2-oate) showed clinical signs in mice consistent with a strong sensitiser in preliminary studies conducted prior to a guideline LLNA. As such, it should be classified as a skin sensitiser (Category 1). The data do not allow distinction between Category 1A and 1B. On a precautionary basis, the substance should be classified as Cat 1A according to EU CLP criteria (EC 1272/2008).