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Administrative data

Description of key information

The assessment of Contact Hypersensitivity to GR-88-0778 was performed in the Mouse (Local Lymph Node Assay) according to the guidelines described in: OECD, Section 4, Health Effects, No.429. Based on these results and according to the recommendations made in the test guidelines (including all amendments), GR-88-0778 would be regarded as skin sensitizer.

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:
11 March 2015 to 08 July 2015
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)
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)
Specific details on test material used for the study:
Name (as stated in the report): GR-88-0778
Lot No: Batch 6
Aspect: Colourless liquid
Expiration date: March 29, 2017
Species:
mouse
Strain:
other: CBA/J
Sex:
female
Details on test animals and environmental conditions:
- Species: Mouse, CBA/J strain, inbred, SPF-Quality. Recognized by the international guidelines as the recommended test system (e.g. OECD, EC, EPA).
- Number of animals: 20 females (nulliparous and non-pregnant), five females per group (main study only).
- Age and body weight: Young adult animals (approx. 10 weeks old) were selected. Body weight variation was within +/- 20% of the sex mean.
- Identification: Tail mark with marker pen.
- Health inspection: At least prior to dosing. It was ensured that the animals were healthy and that the ears were intact and free from any abnormality.
- Room temp: 18 to 24°C
- humidity: 40 to 70%
- Air change: at least 10 air changes/hour
- Light: a 12-hour light/12-hour dark cycle
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
25; 50 and 100%
No. of animals per dose:
5 animals per group/dose
Positive control substance(s):
other: no concurrent positive control group was added to the study.
Positive control results:
no concurrent positive control group was added to the study
Key result
Parameter:
SI
Value:
3
Test group / Remarks:
25% substance concentration
Key result
Parameter:
SI
Value:
7.5
Test group / Remarks:
50% substance concentration
Key result
Parameter:
SI
Value:
8.8
Test group / Remarks:
100% substance concentration
Cellular proliferation data / Observations:
These results indicate that the test substance could elicit a SI ≥ 3. The data showed a dose-response and an EC3 value (the estimated test substance concentration that will give a SI =3) of 25% was determined since the mean SI value of the animals treated at 25% was 3.0.
Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
These results indicate that the test substance could elicit a SI ≥ 3. The data showed a dose-response and an EC3 value (the estimated test substance concentration that will give a SI =3) of 25% was determined since the mean SI value of the animals treated at 25% was 3.0 .Based on these results and according to the recommendations made in the test guidelines (including all amendments), GR-88-0778 would be regarded as skin sensitizer (Cat. 1B).
Executive summary:

Assessment of Contact Hypersensitivity to GR-88-0778 in the Mouse (Local Lymph Node Assay). The study was carried out based on the guidelines described in: OECD, Section 4, Health Effects, No.429 (2010), EC, No 440/2008; B42: "Skin Sensitization: Local Lymph Node Assay" EPA, OPPTS 870.2600 (2003) “Skin Sensitization”. Test substance concentrations selected for the main study were based on the results of a pre-screen test. In the main study, three experimental groups of five female CBA/J mice were treated with test substance concentrations of 25, 50 or 100% w/w on three consecutive days, by open application on the ears. Five vehicle control animals were similarly treated, but with vehicle alone (Acetone/Olive oil (4:1 v/v)). Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised and pooled for each animal. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of Disintegrations Per Minute (DPM) and a stimulation index (SI) was subsequently calculated for each group. Very slight irritation of the ears was shown by the animals treated at 50% and 100% on Days 3 and/ or 4. Scaliness was noted for the animals treated at 100% on Day 6. This was considered not to have a toxicologically significant effect on the activity of the nodes. The auricular lymph nodes of the animals of the control group and animals treated at 25% were considered normal in size. The nodes of the animals treated at 50% and 100% were considered enlarged. 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 substance concentrations 25, 50 and 100% were 1504, 3792 and 4436 DPM, respectively. The mean DPM/animal value for the vehicle control group was 505 DPM. The SI values calculated for the substance concentrations 25, 50 and 100% were 3.0, 7.5 and 8.8, respectively. These results indicate that the test substance could elicit a SI ≥ 3. The data showed a dose-response and an EC3 value (the estimated test substance concentration that will give a SI =3) of 25% was determined since the mean SI value of the animals treated at 25% was 3.0. The six-month reliability check with Alpha-hexylcinnamaldehyde indicates that the Local Lymph Node Assay as performed at WIL Research Europe is an appropriate model for testing for contact hypersensitivity. Based on these results and according to the recommendations made in the test guidelines (including all amendments), GR-88-0778 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

Based on the data available and key results described in this summary, the substance has shown some skin sensitisation potency and should therefore be classified as Skin sensitizer Category 1B according to the (EC) No 1272/2008 Regulation (CLP).