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Description of key information

The results obtained, in these experimental conditions (K1 study, 442B), enable to conclude that test item Socogel Part I does not have to be classified as a skin sensitizer, in accordance with Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.

No signal word or hazard statement is required

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The experiment was performed between 24 January 2018 and 13 March 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 442B (Skin Sensitization: Local Lymph Node Assay: BrdU-ELISA)
Version / remarks:
22 July 2010
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: test method B.51 of the council regulation No.640/2012
Version / remarks:
dated 06 July 2012
Deviations:
no
GLP compliance:
yes
Remarks:
27 Avril 2017
Type of study:
mouse local lymph node assay (LLNA): BrdU-ELISA
Specific details on test material used for the study:
- Name of test material (as cited in study report): Socogel Part I
- Physical state: colorless to yellowish liquid
- Analytical purity: not applicable; considered as 100 % for the study
Species:
mouse
Strain:
CBA:J
Sex:
female
Details on test animals and environmental conditions:
Supplied by Elevage Janvier Labs (F-53941 Le Genest Saint Isle).
Randomly allocated to cages.
Nulliparous and non-pregnant.
After an acclimatisation period of at least five days under stabling and nutritional conditions identical to those of the test, the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.
At the start of the main study the animals were 8 weeks old.
Housed in suspended solid-floor polypropylene cages furnished with softwood wood flakes.
Temperature and relative humidity were controlled to remain within target ranges of 19°C to 25°C and 30% to 70%, respectively.
The drinking water (tap water from public distribution system) and food (ENVIGO 2016) were supplied ad libitum. Microbiological and chemical analyses of the water were carried out once every six months.
The standard study plan related to this study was approved by the registered Ethics Committee No. 76.
The study was performed in accordance with the guidelines regarding the care and use of animals for experimental procedures:
- the European Communities Council Directive 2010/63/UE of 22 September 2010
- the French Decree No. 2013-118 of 01 February 2013.
Vehicle:
dimethylformamide
Concentration:
0, 25%, 50, 100%
No. of animals per dose:
4 animals
Details on study design:
Preliminary study: Mouse was treated by daily application of 25 μL of the test item undiluted (100%) to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). The mouse was observed daily from Day 1. Any signs of toxicity or excessive local irritation noted during this period were recorded. Ear thickness was recorded on Day 1, Day 3 and on Day 6. The bodyweight of the mouse was recorded on Day 1 (prior to dosing) and Day 6.
Main study:
Groups of four mice daily treated with the test item undiluted (100%) and diluted at 50% and 25% in DMF on the dorsal surface of each ear for three consecutive days (Days 1, 2 and 3).
Test item formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette.
Clinical observations and mortality observed daily on Days 1, 2, 3, 4, 5 and 6.
Bodyweights each mouse was recorded on Day 1 (prior to dosing) and Day 6 (prior to termination).
Ear thickness measurements and recording of local reactions were performed in order to assess any possible irritant effect of the test item.

On day 5, 0.5 mL (5 mg/mouse) of BrdU (10 mg/mL) solution was injected by intra-peritoneal route. The Brdu solution was prepared by weighing 202.3 mg of 5-bromo-2'-deoxyuridine (SIGMA – Batch No. HMBF5970V) in a glass sample bottle and adding 20.23 mL of physiological saline.
On Day 6 (end of the test), the animals were euthanized with sodium pentobarbital (Dolethal®).
The draining auricular lymph nodes from the four mice were excised. From each mouse, a single-cell suspension of lymph node cells (LNC) excised bilaterally was prepared by gentle mechanical disaggregation through a disposable plastic pestle to crush the lymph nodes. BrdU was measured by ELISA using a commercial kit
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
No
Positive control results:
Three groups, each of four animals, were treated with 50 μL (25 μL per ear) of α- Hexylcinnamaldehyde, as a solution in acetone/olive oil (4:1, v/v) at concentrations of 5%, 10% and 25% (v/v). A further control group of four animals was treated with acetone/olive oil (4:1, v/v) alone.
At 25%, the SI is 1.85. The global EC 1.6 is 14.58%. In conclusion, in view of these results, under these experimental conditions, the substance a-Hexylcinnamaldehyde in accordance with the Regulation (EC) No. 1272/2008 has to be classified in category 1 “Skin sensitisation”.
The signal word “Warning” and hazard statement H317 “May cause an allergic skin reaction” are required.
Key result
Parameter:
SI
Value:
1.01
Variability:
+-0.09
Test group / Remarks:
25% concentration
Key result
Parameter:
SI
Value:
1.17
Variability:
+-0.13
Test group / Remarks:
50% concentration
Key result
Parameter:
SI
Value:
0.93
Variability:
+-0.1
Test group / Remarks:
100% concentration
Key result
Parameter:
other: EC1.6
Remarks on result:
not determinable
Remarks:
No SI superior to 1.6
Cellular proliferation data / Observations:
The Stimulation Index (SI) calculated by individual approach was 1.01, 1.17 and 0.93 for the treated groups at 25%, 50% and 100%, respectively.
Therefore, the EC1.6 cannot be determined due to the absence of SI value higher than 1.6.

No mortality and no signs of systemic toxicity were noted in the test and control animals during the test.

Bodyweight changes of the test animals between Day 1 and Day 6 were comparable to those observed in the corresponding control group animals over the same period.

Dryness of the skin was noted in all animals treated at 100% on day 6.

No increase in ear thickness and in ear weight was noted in animals treated at 25%, 50% and 100%.

Therefore, the test item has to be considered as not excessively irritant at these concentrations.

Interpretation of results:
GHS criteria not met
Conclusions:
EC1.6 cannot be determined due to the absence of SI value higher than 1.6.
The results obtained, in these experimental conditions, enable to conclude that test item Socogel Part I does not have to be classified as a skin sensitizer, in accordance with Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.
No signal word or hazard statement is required.
Executive summary:

The test was performed to assess the skin sensitisation potential of test item Socogel Part I in the CBA/J strain mouse following topical applications to the dorsal surface of the ear. The basic principle underlying the LLNA:BrdU is that sensitizers induce proliferation of lymphocytes in the lymph nodes draining the site of test item application.

Three groups of four animals were treated for three consecutive days (D1, D2, D3) with 50 μL (25 μL per ear) of the test item at 100% and diluted at concentrations of 50% and 25% in N,N-dimethylformamide (DMF). A further group of four animals was treated with DMF.

On D5, 0.5 mL of BrdU solution (10 mg/mL) was injected by the intraperitoneal route.

On D6, the proliferation of lymphocytes in the draining auricular lymph nodes was determined by the measurement of BrdU content in DNA of lymphocyte using an ELISA kit.

The experimental protocol was established in accordance with O.E.C.D. Test Guideline No.442-B of 22 July 2010 and test method B.51 of the council regulation No.640/2012 dated 06 July 2012.

No mortality and no signs of systemic toxicity were noted in the test and control animals during the test.

Dryness of the skin was noted in all animals treated at 100% on day 6.

No increase in ear thickness and in ear weight was noted in animals treated at 25%, 50% and 100%.

Therefore, the test item has to be considered as not excessively irritant at these concentrations.

The Stimulation Index (SI) calculated by individual approach was 1.01, 1.17 and 0.93 for the treated groups at 25%, 50% and 100%, respectively.

Therefore, the EC1.6 cannot be determined due to the absence of SI value higher than 1.6.

The results obtained, in these experimental conditions, enable to conclude that test item Socogel Part I does not have to be classified as a skin sensitizer, in accordance with Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.

No signal word or hazard statement is required.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

EC1.6 cannot be determined due to the absence of SI value higher than 1.6.

The results obtained, in these experimental conditions, enable to conclude that test item Socogel Part I does not have to be classified as a skin sensitizer, in accordance with Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures.

No signal word or hazard statement is required.