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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
07 October 2015 to 26 October 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
For category justification, see IUCLID section 13
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes (incl. QA statement)
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: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 10 weeks old
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Makrolon cages containing sterilised sawdust
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
2, 15 and 30 % test item w/w
No. of animals per dose:
5
Details on study design:
RANGE FINDING TESTS: 15 and 30 % test item w/w using 2 animals per concentration

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 days
- Test groups: 5 animals exposed to each concentration
- Control group: 5 animals exposed to the vehicle
- Site: dorsal surface of both ears
- Frequency of applications: Days 1, 2, 3
- Duration: 6 days
- Concentrations: 2, 15 and 30 % test item w/w

SCORE:
Erythema and eschar formation:
No erythema - 0
Very slight erythema (barely perceptible) - 1
Well-defined erythema - 2
Moderate to severe erythema (beet redness) to slight eschar formation (injuries in depth) - 3
Severe erythema (beet redness) to eschar formation preventing grading of erythema - 4
Positive control substance(s):
other: no
Positive control results:
A reliability check is carried out at regular intervals to check the sensitivity of the test system and the reliability of the experimental techniques used at the laboratory. The last check was performed in April 2015. The SI values calculated for the item concentrations 5, 10 and 25% were 1.7, 3.0 and 9.1 respectively. An EC3 value of 10% was calculated using linear interpolation. The calculated EC3 value was found to be in the acceptable range of 4.8 and 19.5%. The results of the 6 monthly HCA reliability checks of the recent years were 16.5, 14.5, 13.4, 14.1, 17.3 and 9.8%. Based on the results, it was concluded that the Local Lymph Node Assay as performed at the laboratory is an appropriate model for testing for contact hypersensitivity.
Parameter:
SI
Value:
1
Test group / Remarks:
Test item concentration = 2%
Parameter:
SI
Value:
0.9
Test group / Remarks:
Test item concentration = 15%
Parameter:
SI
Value:
0.6
Test group / Remarks:
Test item concentration = 30%
Parameter:
EC3
Value:
> 30

No irritation and no signs of systemic toxicity were observed in any of the animals.

No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size.

No macroscopic abnormalities of the surrounding area were noted for any of the animals.

Mean DPM/animal values for the experimental groups treated with test item concentrations 2, 15 and 30% were 899, 780 and 584 DPM, respectively. The mean DPM/animal value for the vehicle control group was 911 DPM. The SI values calculated for the item concentrations 2, 15 and 30% were 1.0, 0.9 and 0.6, respectively.

Interpretation of results:
GHS criteria not met
Conclusions:
Dilithium adipate would not be regarded as a skin sensitizer.
Executive summary:

This study is carried out in accordance to OECD guideline 429, EU method B.42 and is GLP compliant. Therefore, it is given reliability rating of 1 (reliable without restrictions). Dilithium adipate would not be regarded as a skin sensitizer.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The substances in the category are considered to be similar on the basis that they have common structures of a lithium ion varying only by the length of the fatty acid chain. As a result, it is expected that the substances will have similar, predictable properties. REACH Annex V, Entry 9, groups fatty acids and their potassium, sodium, calcium and magnesium salts, including C6 to C24, predominantly even-numbered, unbranched, saturated or unsaturated aliphatic monocarboxylic acids. Since published reviews do not distinguish between the properties of monocarboxylic or dicarboxylic acids as a category, then the same interpretation can be applied to the dicarboxylic acids. Due to the close structural similarity and the narrow range of carbon chain numbers covered in this category, the sensitisation potential is expected to be similar across the category.

Dilithium adipate (C6) was subjected to a Local Lymph Node Assay (LLNA) in mice according to OECD Guideline 429. This substance was chosen since it had the highest relative lithium content and the lowest carbon chain length. The test material was considered to be a non-sensitiser under the conditions of the test, with the highest Stimulation Index of 1.0 at 2% concentration in acetone/olive oil, with the EC3 value being >30% (the highest concentration tested).

An additional supporting LLNA study on the skin sensitisation potential of the monocarboxylate fatty acids C18 (unsaturated) lithium salts has also been considered. This substance was also a non-sensitiser under the conditions of the test with the highest Stimulation Index of 1.68 at 10% concentration in ethanol/distilled water.

On the basis of the category justification and the preamble to this endpoint, it is justifiable to read across the negative result from sensitisation study on dilithium adipate to the other members of the category, and together with the negative result from the fatty acids C18 (unsaturated) lithium salts study, this supports the lack of sensitisation potential of the dilithium salts of dicarboxylic fatty acids in the C6 – C10 category.


Short description of key information:
Local Lymph Node Assay: Stimulation Index <3 at the highest concentration tested.

Justification for selection of skin sensitisation endpoint:
This substance is representative of the lithium salts of C6-C10 fatty acids and can be read across to other lithium dicarboxylate category members.

Justification for classification or non-classification

No classification required. Stimulation Index <3 in a LLNA.

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