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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

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Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Test performed in 2008.
LLNA method (OECD 442 B) was adopted in 2010.
Specific details on test material used for the study:
Test item:
Sponsor's identification: LCE07106
Container: plastic flask (n=1)
Quantity: 184.84 g (container + contents)
Batch n° 0715200018
Production data: 01 June 2007
Date received: 21 December 2007
Form: liquid
Colour: yellow
Storage: Room temperature
Re-test date: 31 May 2009
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (F-69592 L'Arbresle)
- Age at study initiation: 4 weeks old
- Weight at study initiation: between 232 and 283 g
- Housing: The animals were housed either in groups of 2 or 3 in polycarbonate containers, the flooring of which was covered with dust-free cuttings and the top fitted a stainless steel lid with a feeding device and drinking device of 500 ml.
- Food and drink: The drinking water (tap water from public distribution system) and food were supplied freely. Microbiological verification and chemical analysis were conducted every six months by the Institut Européen de l'Environnement de Bordeaux (I.E.E.B).
- Acclimation period: The animals were kept for a minimum acclimatisation period of 5 days, under stabling and nutritional conditions identical to those of the test.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 19 and 22 °C
- Humidity (%): between 45 and 70 %
- Lighting time:12 hours daily
Route:
intradermal and epicutaneous
Concentration / amount:
Day 0
After shearing the scapular zone, three pair of intradermal injections of 0.1 ml were performed on the scapular zone in such a way as an injection on each pair is placed to either side of the spine as follows:
Group 2 (treated):
2 ID: Freund's Complete Adjuvant diluted by 50% in isotonic sodium chloride
2 ID: test item at 0.39%
2 ID: a test mixture with equal volumes v/v
- Freund's Complete Adjuvant at 50% and the test item at 0.78%
Day 6
The scapular zone of all animals in each group was shorn.
Day 7
A topical application under occlusive dressing for 48 hours was performed on the injection sites of each animal.
Group 2 (treated):
0.5 ml of the test item at 100%. After the removal of the patch, the treated areas were rinsed with distilled water.
Day(s)/duration:
The induction phase lasts 7 days
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
12.5 % (Maximal Non Irritant Concentration) and 6.25 % (1/2 MNIC)
Day(s)/duration:
the treatment lasts 24 hours for each concentration
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Negative control group: 5 animals
Treated group: 10 animals
Details on study design:
INDUCTION PHASE
Day 0
After shearing the scapular zone, three pair of intradermal injections of 0.1 ml were performed on the scapular zone in such a way as an injection on each pair is placed to either side of the spine as follows:
Group 1 (negative control):
2 ID: Freund's Complete Adujuvant diluted by 50 % in isotonic sodium chloride
2 ID: isotonic sodium chloride
2 ID: a mixture with equal volumes v/v:
-Freund's Complete Adjuvant at 50 % and isotonic sodium chloride
Group 2 (treated):
2 ID: Freund's Complete Adjuvant diluted by 50% in isotonic sodium chloride
2 ID: test item at 0.39%
2 ID: a test mixture with equal volumes v/v
- Freund's Complete Adjuvant at 50% and the test item at 0.78%
Day 6
The scapular zone of all animals in each group was shorn.
Day 7
A topical application under occlusive dressing for 48 hours was performed on the injection sites of each animal.
Group 1 (negative control):
0.5 ml of distilled water
Group 2 (treated):
0.5 ml of the test item at 100%. After the removal of the patch, the treated areas were rinsed with distilled water.

REST PHASE
The animals of both groups were left for 10 days

CHALLENGE PHASE
Day 20
The experimental procedure of this phase was identical for both groups GROUP 1 (Negative control) and GROUP 2 (treated) submitted to this experimentation: on the previously shorn dorso-lumbar zone, an application on either side of the spine, under occlusive dressing, was performed during 24 hours:
- 1 sample cup containing the test item at 12.5% (MNIC) and at 6.25 % (1/2 MNIC)
Challenge controls:
The Group 1 (negative control) was submitted to the same experimentation as Group 2 (treated group) during the challenge phase.
Positive control substance(s):
yes
Positive control results:
Reference substance: alpha-Hexylcinnamaldehyde / CAS n° 101-86-0
Treated animals number: 10
In conclusion, in view of these results, under these experimental conditions, the substance alpha-Hexylcinnamaldehyde;
must be classified R 43 “may cause sensitization by skin contact” in accordance with the criteria for classification, packaging and labelling of dangerous substances and preparations of the E.E.C. Directives 67/548, 2001/59 and 99/45. This substance must be characterised by the symbol “Xi' and the warming label “Irritant”.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
12.5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No visible modification
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
12.5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No visible modification
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
12.5 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No visible modification
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
12.5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No visible modification
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
6.25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No visible modification
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
6.25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No visible modification
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
6.25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No visible modification
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
6.25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No visible modification
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
In view of these results, under these experimental conditions, the test item LCE07106 must not be classified, in accordance with the criteria for classification, packaging and labelling of dangerous substances and preparations of the E.E.C. Directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required.
In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must not be classified in category 1. No signal word and hazard statement are required.
Executive summary:

SUMMARY AND CONCLUSION OF THE STUDY

The aim of the study was to evaluate the possible allergenic activity of the test item LCE07106 after intradermic injection and topical administration in guinea pigs.

After induction (intradermic injection at 0.39% and topical application at 100%) of 10 Guinea Pigs of treated group with the test item LCE07106 and a 10-day rest phase, the challenge phase, under occlusive dressing for 24 hours, consisted to a single topical application of the test item diluted at 12.5% and at 6.25% in distilled water. The experimental protocol was established according the O.E.C.D. guideline n°406 dated July 17", 1992 and the method B6 of the E.E.C. n°96/54 dated July 30th, 1996.

No macroscopic cutaneous reactions attributable to allergy was recorded during the examination following the removal of the occlusive dressing (challenge phase) from the animals of the treated group with the test item. No cutaneous intolerance reaction was recorded in animals from the negative control group.

In conclusion, in view of these results, under these experimental conditions, the test item LCE07106 must not classified, in accordance with the criteria for classification, packaging and labelling of dangerous substances and preparations of the E.E.C. Directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required. In accordance with the Globally Harmonized System (COM(2007)355 final), the test item must not be classified in category 1. No signal word and hazard statement are required.

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

Skin sensitisation

In view of these results, under these experimental conditions, the test item must not be classified, in accordance with the criteria for classification, packaging and labelling of dangerous substances and preparations of the E.E.C. Directives 67/548, 2001/59 and 99/45. No symbol and risk phrase are required.

In accordance with the Globally Harmonized System (COMC2007)355 final), the test item must not be classified in category 1. No signal word and hazard statement are required.