Registration Dossier

Administrative data

Description of key information

An OECD test n°406 is available with the registered substance.

After induction (intradermic injection and topical application) of 21 Guinea Pigs (female) of treated group with the pure test product and a 17 days rest phase, the challenge phase, under occlusive dressing for 24 hours, consisted to a single topical application of the test product at 100% and diluted at 50%, according to the experimental protocol established from the O.E.C.D. guideline n°406.
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 product.
No cutaneous intolerance reaction was recorded in animals from the negative control group.
In conclusion, under these experimental conditions, the test item must not be classified.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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:
other: GLP study, OECD guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
2001-04-18
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
In 2001, guinea pig maximisation test was as much considered as the LLNA test to evaluate the skin sensitization potiential of a substance
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
32 albinos guinea pigs of Dunkin-Hartley strain, supplied by Elevage St Antoine (F-22740 Pleudaniel)
were exposed to the test product after a 5-day acclimatisation period. For the main study, the animals
weighted between 300 g and 352 g at the beginning of the test.
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
25%
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%

No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100%
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
50 %
No. of animals per dose:
Number of animals in test group: 21 females
Number of animals in negative control group: 11 females
Details on study design:
Preliminary studies
Maximum Non Necrotizing Concentration (M.N.N.C.) determination:
2 females guinea pigs identified C5536 and C5537 were used.
The test product was injected by intradermal route at the following concentrations: pure (100%), 50%,
25%, 12.5%, 6.25% and 3.125% diluted in a physiological saline solution.
Pre-Maximum Non Irritant Concentration (M.N.I.C.) determination:
2 females guinea pigs identified C5536 and C5537 were used.
The product was applied under an occlusive dressing during 24 hours, at the following concentrations
pure (100%) and diluted at 50%, 25% and 12.5% in a physiological saline solution.
Maximum Non Irritant Concentration (M.N.I.C.) determination:
3 females guinea pigs identified C5538 to C5540 were used.
After induction by intradermal injection with physiological saline solution and by topical application
with distilled water and a 17 days rest phase, the challenge phase under occlusive dressing for 24
hours consists in a single topical application of the test product at the following concentrations pure
(100 and diluted at 50%, 25% and 12.5% in distilled water.

Main study
GROUP 1 (negative control) : 11 females guinea pigs identified C5580 to C5590;
GROUP 2 (treated) : 21 females guinea pigs identified C5612 to C5632;
Note: The results of the 3 latest positive group (Reference substance : neomycin sulfate Test 3 and
benzocaïne Test 4 and 5) carried out as method sensibility, were presented in appendix.
The environmental parameters were:
- Temperature : between 20 °C and 24 °C
- Relative humidity : between 42% and 67%
2.2 - Chronological development
# Preliminary studies
06/14/01 Arrival of animals.
06/18/01 to 07/18/01 Preliminary tests: pre MNIC, MNNC, and MNIC determinations.
# Main study
06/21/01 Arrival of animals.
Induction phase
06/26/01 1st induction:
- 2 intradermal injections of the product diluted at 25% in a physiological
saline solution.
- 2 intradermal injections of Freund’s Complete Adjuvant diluted at 50% in a
physiological saline solution.
- 2 intradermal injections of a mixture with equal volumes - Freund’s
Complete Adjuvant at 50% and the product diluted at 25% in a physiological
saline solution.
06/26/01 Weighing of animals.
07/04/01 2nd induction: topical application, on the same zone, with the product at
100%, 24 hours after brushing with 0.5 ml of a solution of Sodium lauryl
sulfate at 10%.
07/06/01 to 07/23/01 Rest phase: 17 days
07/23/01 Challenge phase: topical application under occlusive dressing at the
following concentrations100% and 50%.
07/25/01 24-hours reading time.
07/26/01 48-hours reading time and weighing.
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
21
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 21.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
21
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 21.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
21
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 21.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
21
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 21.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
21
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 21.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
21
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 21.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
21
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 21.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test group
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
21
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50 %. No with. + reactions: 0.0. Total no. in groups: 21.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
11
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 11.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
11
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 11.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
11
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 11.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
11
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 11.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
11
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 11.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
11
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 11.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
11
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 11.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
11
Remarks on result:
no indication of skin sensitisation
Remarks:
Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 11.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
75%
Remarks on result:
positive indication of skin sensitisation

Maximum concentration not causing irritating effects in preliminary test: 100 %

Signs of irritation during induction:
none

Application of sodium laurylsulfate at 10 % at day 7

Evidence of sensitisation of each challenge concentration:
No evidence

Interpretation of results:
not sensitising
Remarks:
Migrated information not classified Criteria used for interpretation of results: EU
Conclusions:
In view of these results, under these experimental conditions, the product LCA01006, in accordance
with the criteria for classification, packaging and labelling of dangerous substances of the E.E.C.
Directives 67/548 and 93/21, must not be classified “R43 may cause sensitisation by skin contact”.
Executive summary:

After induction (intradermic injection and topical application) of 21 Guinea Pigs (female) of treated group with the pure test product LCA01006 and a 17 days rest phase, the challenge phase, under occlusive dressing for 24 hours, consisted to a single topical application of the test product at 100% and diluted at 50%, according to the experimental protocol established from the O.E.C.D. guideline n°406 dated July 17th,1992 and the method B.6 of the directive 92/69/EEC dated December 29th,1992.

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 product LCA01006.

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 product LCA01006, in accordance with the criteria for classification, packaging and labelling of dangerous substances of the E.E.C. Directives 67/548 and 93/21, must not be classified.

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

According to the results of the OECD test n°406, and the criteria for classification, packaging and labelling of dangerous substances of the CLP regulation n°1272/2008/EC, the test item must not be classified as a skin sensitizer.