Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Skin weakly sensitizing

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:
Feb - May 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
Balb/c
Sex:
female
Details on test animals and environmental conditions:
Animal species and strain: Mouse, Balb/c strain, inbred, SPF-Quality.
Breeder/supplier: Charles River Deutschland, Sulzfeld, Germany.
Number of animals 30 females (nulliparous and non-pregnant), six females per group.
Age: Approximately 9 weeks (at initiation of treatment).
Body weight range: 17 to 20 gram (at initiation of treatment).
Health Check: A health inspection was performed prior to treatment, to ensure that the animals are in a good state of health. Special attention was paid to the ears, which were intact and free from any abnormality.
Vehicle:
other: DAE433 (Merck, Darmstadt, Germany)
Concentration:
Concentrations of 25% and 50% were tested and the highest concentration was the maximum concentration as required in the test guidelines (50% for solids).
No. of animals per dose:
Three groups of six animals were treated with one test item concentration per group. The highest test item concentration was selected from the pre-screen test. One group of six animals was treated with vehicle and one group with the positive control item.
Details on study design:
Induction - Days 1, 2 and 3
For the experimental animals, the dorsal surface of both ears was epidermally treated (25 μL/ear) with the test item concentration, approximately the same time each day. The concentrations were mixed thoroughly using a magnetic stirrer immediately prior to dosing.
The control animals were treated as described for the experimental animals, except that, instead of the test item, the vehicle or positive control item was administered.
Positive control substance(s):
other: 0.5% 1-Chloro-2,4-Dinitrobenzene (DNCB)
Statistics:
Calculations were performed in MS EXCEL and statistical analysis was performed with GraphPad Prism 4 (Kruskal-Wallis test, followed by the Mann Whitney test).
Positive control results:
The positive control item DNCB elicited a reaction pattern with increased LN hyperplasia, which was in congruence with the expected mode of action of a contact allergen.
Key result
Parameter:
other: Ear weight index
Value:
ca. 1.13
Test group / Remarks:
0.5% LEE011-A3
Key result
Parameter:
other: Ear weight index
Value:
ca. 1.1
Test group / Remarks:
5% LEE011-A3
Key result
Parameter:
other: Ear weight index
Value:
ca. 1.05
Test group / Remarks:
50% LEE011-A3
Key result
Parameter:
other: LN weight index
Value:
ca. 1.19
Test group / Remarks:
0.5% LEE011-A3
Key result
Parameter:
other: LN weight index
Value:
ca. 1.16
Test group / Remarks:
5% LEE011-A3
Key result
Parameter:
other: LN weight index
Value:
ca. 1.17
Test group / Remarks:
50% LEE011-A3
Key result
Parameter:
other: Cell count index
Value:
ca. 1.04
Test group / Remarks:
0.5% LEE011-A3
Key result
Parameter:
other: Cell count index
Value:
ca. 1.2
Test group / Remarks:
5% LEE011-A3
Key result
Parameter:
other: Cell count index
Value:
ca. 1.44
Test group / Remarks:
50% LEE011-A3
Key result
Parameter:
SI
Test group / Remarks:
LEE011-A3: 0.5% (w/w)
Remarks on result:
not measured/tested
Key result
Parameter:
SI
Test group / Remarks:
LEE011-A3: 5%
Remarks on result:
not measured/tested
Key result
Parameter:
SI
Test group / Remarks:
LEE011-A3: 50% (w/w)
Remarks on result:
not measured/tested
Cellular proliferation data / Observations:
LEE011-A3 exceeded the ear weight threshold at all concentrations with statistical significance at 0.5% and 5% when compared to vehicle. No clear dose response was found.
LEE011-A3 did not cause any relevant changes in LN weight up to a concentration of 50% in DAE433.
LEE011-A3 exceeded the LN count threshold at 50% with statistical significance when compared to vehicle and showed a clear dose response.

No irritation of the ears was noted after visual examination in the majority of animals. Brown testsubstance remnants on the dorsal surface of the ears of the animals treated at 50% (between Days 1-3) did not hamper scoring for erythema. Visual examination of the nodes revealed that all the nodes of the experimental animals were considered normal in size when compared to the vehicle control group. No macroscopic abnormalities of the surrounding areas were noted in any of the animals.

Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. There were no clinical observations attributable to treatment with LEE011-A3.

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
In conclusion, LEE011-A3 appeared to be a weak sensitizer with weak irritating potential in the murine LLNA TIER I.
Based on these results:
according to the recommendations made in the test guidelines (including all amendments), LEE011-A3 would be regarded as skin sensitizer.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

LEE011-A3 appeared to be a weak sensitizer with weak irritating potential in the murine LLNA TIER I.

Based on these results:

according to the recommendations made in the test guidelines (including all amendments), LEE011-A3 would be regarded as skin sensitizer.