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Diss Factsheets

Administrative data

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:
experimental study
Adequacy of study:
key study
Study period:
From 6 October 2014 to 15 December 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well described study performed according to OECD guideline and GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/J Rj
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: ELEVAGE JANVIER, Route des Chènes Secs B.P. 4105, 53940 LE GENEST-ST-ISLE, France
- Age at study initiation: 8 weeks old
- Weight at study initiation: 20.1-21.6 g
- Housing: Group caging (Cage type: Type II. polypropylene / polycarbonate)
- Diet: ssniff® SM Rat/Mouse – “Breeding & Maintenance, 15 mm, autoclavable Complete diet for rats/mice” produced by ssniff Spezialdiäten GmbH (Ferdinand-Gabriel-Weg 16, D-59494 Soest, Germany), ad libitum.
- Water: tap water from the municipal supply from 500 mL bottle, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19.8-25.0°C
- Humidity: 31-70 %
- Air changes: 15-20 air exchanges/hour
- Photoperiod: light 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: 16 October 2014 To: 27 October 2014
Vehicle:
dimethyl sulphoxide
Concentration:
25, 10 and 5% (w/v)
No. of animals per dose:
4 female mice
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: based on the results of the preliminary solubility / compatibility test, the test item was formulated in Dimethyl sulfoxide. The highest achievable concentration was 25% (w/v).
- Irritation: the Preliminary Irritation / Toxicity Test was performed in CBA/J Rj mice using two doses (25 and 10% (w/v) in DMSO). Based on the observations recorded in the preliminary test, 25% (w/v) was selected as top dose for the main test.
- Lymph node proliferation response: not measured

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: randomisation
- Criteria used to consider a positive response:
The test item is regarded as a sensitizer if both of the following criteria are fulfilled:
1) That exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than recorded in control mice, as indicated by the stimulation index.
2) The data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.

TREATMENT PREPARATION AND ADMINISTRATION:
In the main assay, twenty female CBA/J Rj mice were allocated to five groups of four animals each:
- three groups received R0056895A (formulated in DMSO) at 25, 10 and 5% (w/v) concentrations,
- the negative control group received the vehicle (DMSO),
- the positive control group received 25% (w/v) HCA (dissolved in DMSO).
The test item solutions were applied on the dorsal surface of ears of experimental animals (25 μL/ear) for three consecutive days (Days 1, 2 and 3). There was no treatment on Days 4, 5 and 6. On Day 6, the cell proliferation in the local lymph nodes was measured by incorporation of tritiated methyl thymidine (3HTdR) and the values obtained were used to calculate stimulation indices (SI).
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Positive control results:
No mortality, cutaneous reactions or signs of toxicity were observed for the positive control substance in the study. A significant lymphoproliferative response (stimulation index value of 5.8) was noted for HCA in the main experiment. The DPN values observed for the positive control substance in this experiment were within the historical control range.
Parameter:
SI
Remarks on result:
other: The stimulation index values were 1.2, 1.4 and 2.1 at concentrations of 25, 10 and 5% (w/v), respectively. See table below.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: See table below

Clinical signs:

No mortality or signs of systemic toxicity were observed during the study. Test item precipitate (in the 25% and 10% dose groups) / minimal amount of test item precipitate (in the 5% dose group) was observed on the ears of the animals in all test item treated groups on Days 1-3. There were no indications of any irritancy at the site of application.

Body weight:

No treatment related effects were observed on body weights.

Ear thickness measurement:

Increased ear thickness values were recorded for several test item treated animals on Day 3 and/or Day 6, but none of these values were above the regulatory threshold of 25% (as limit of positivity). The biopsy weights were within the historical control range for all test item treated animals.

Increased ear thickness values (over the limit of positivity) were detected for positive control animals on Day 6, although the biopsy weights were in the historical control range in the positive control group.

Proliferation assay:

Table 1: DPM, DPN and Stimulation Index Values for all Groups

Test Group Name

Measured DPM / group

DPM

Number
of lymph nodes

DPN

Stimulation Index

Background
(5% (w/v) TCA)

30
32

-

-

-

-

Negative (vehicle) control
(DMSO)

3846

3815.0

8

476.9

1.0

R0056895A
(25% (w/v) in DMSO)

4511

4480.0

8

560.0

1.2

R0056895A
(10% (w/v) in DMSO)

5192

5161.0

8

645.1

1.4

R0056895A
(5% (w/v) in DMSO)

7974

7943.0

8

992.9

2.1

Positive control

(25% (w/v) HCA in DMSO)

21984

21953.0

8

2744.1

5.8

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
R0056895A, tested at up to 25% in DMSO, was shown to have no sensitisation potential (non-sensitizer) in the Local Lymph Node Assay.
Executive summary:

The skin sensitisation potential of R0056895A was tested in a Local Lymph Node Assay in mice according to OECD Guidelines No. 429 annd Commission Regulation (EC) No 440/2008, B.42. CBA/J Rj mice received CBA/J Rj mice at 25, 10 and 5% (w/v) in DMSO.

No mortality or signs of systemic toxicity were observed during the study. No treatment related body weight loss was observed in the test item treated animals.

The stimulation index values were 1.2, 1.4 and 2.1 at concentrations of 25, 10 and 5% (w/v), respectively. A significant lymphoproliferative response (stimulation index value of 5.8) was noted for the positive control chemical, this result confirmed the validity of the assay.

In conclusion, under the conditions of the assay, R0056895A was shown to have no sensitisation potential (non-sensitizer) in the Local Lymph Node Assay.

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

The skin sensitisation potential of R0056895A was tested in a Local Lymph Node Assay in mice according to OECD Guidelines No. 429 annd Commission Regulation (EC) No 440/2008, B.42. CBA/J Rj mice received CBA/J Rj mice at 25, 10 and 5% (w/v) in DMSO.

No mortality or signs of systemic toxicity were observed during the study. No treatment related body weight loss was observed in the test item treated animals.

The stimulation index values were 1.2, 1.4 and 2.1 at concentrations of 25, 10 and 5% (w/v), respectively. A significant lymphoproliferative response (stimulation index value of 5.8) was noted for the positive control chemical, this result confirmed the validity of the assay.

In conclusion, under the conditions of the assay, R0056895A was shown to have no sensitisation potential (non-sensitizer) in the Local Lymph Node Assay.


Migrated from Short description of key information:
LLNA: not sensitising (SI ≤ 2.1)

Justification for selection of skin sensitisation endpoint:
Only one study, well described and performed according to OECD guideline and GLP

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to the CLP criteria and based on the study available (LLNA with SI ≤ 2.1), R0056895A is not classified for skin sensitisation.