Registration Dossier

Administrative data

Description of key information

Not sensitising (OECD 406, GLP, K, rel.1)

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
Study period:
20 March to 27 April 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to OECD Guideline 406 with deviations: age at study initiation, housing and feeding conditions not reported. These deviations do not affect the quality of the study and are not considered to be relevant.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
age at study initiation, housing and feeding conditions not reported
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
13 December 2005
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
At the time of study completion (2006), the LLNA OECD test method was not adopted.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL- Source and lot/batch No.of test material: MANE FILS SA / 713060- Physical state: Colourless liquid- Date received: 13 March 2006- Expiration date of the lot/batch: February 2007- Purity test date: February 2006- Test item was considered at 100% for the study.STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: Room temperature
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Centre de production Animale (F-45160 Olivet)- Weight at study initiation: 348-498 g- Housing: No data- Diet: No data- Water: No data- Acclimation period: 5 daysENVIRONMENTAL CONDITIONS- Temperature: 20-23 °C- Humidity: 28-53 %IN-LIFE DATES: 20 March to 27 April 2006
Route:
intradermal
Vehicle:
olive oil
Concentration / amount:
intradermic injection at 3.125%
Day(s)/duration:
8 days
Adequacy of induction:
other: no necrosis has been observed, at the concentration of 3.125%, the first induction has been carried out by intradermal injection at the same concentration
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
topical application at 100%
Day(s)/duration:
3 days
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
topical application at 100 and 50%
Day(s)/duration:
3 days
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
3 males and 2 females for negative control group5 males and 5 females for treated group
Details on study design:
PRELIMINARY TESTS: Maximum Non Necrotizing Concentration (M.N.N.C.) determination: 2 male guinea pigs were used. The test item was injected by intradermal route at the following concentrations: 100%, diluted at 50%, 25%, 12.5%, 6.25% and 3.125% in olive oil. No necrosis has been observed, at the concentration of 3.125%, the first induction has been carried out by intradermal injection at the same concentration.Pre-Maximum Non Irritant Concentration (Pre -M.N.I.C.) determination: 2 male guinea pigs were used. The test item was applied under an occlusive dressing during 24 hours, at the following concentrations 100%, diluted at 50%, 25% and 12.5% in paraffin oil. 24 hours after the removal of the occlusive dressings, no cutaneous reaction was recorded. In view of these results, the concentration selected was 100% for the 2nd induction of the main study and the MNIC determination began at this concentration of 100%.Maximum Non Irritant Concentration (M.N.I.C.) determination: 3 female guinea pigs were used. After induction by intradermal injection with olive oil and by topical application with paraffin oil and a 17-day rest phase, the challenge phase under occlusive dressing for 24 hours consists in a single topical application of the test item at the following concentrations: 100%, diluted at 50%, 25% and 12.5% in paraffin oil. 24 hours after removal of the occlusive dressings, no cutaneous reaction was recorded. In view of this result, the concentrations selected were 100% (MNIC) and 50% (1/2 MNIC) for the challenge phase. MAIN STUDY A. INDUCTION EXPOSURE (INTRADERMAL - 1st induction: Day 0) - No. of exposures: One - 2 intradermal injections of the test item at 3.125%; 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 test item at 6.25%. - Exposure period: Day 0-6 - Duration: 7 days - Concentrations: 3.125% in olive oil B. INDUCTION EXPOSURE (TOPICAL - 2nd induction: Day 7) - No. of exposures: One - Topical application, on the same zone, with the test item at 100%, 24 hours after brushing with 0.5 mL of a solution of Sodium lauryl sulfate at 10%. - Duration: 3 days - Concentrations: 100% C. REST PHASE: 17 days D. CHALLENGE EXPOSURE - No. of exposures: One - Day(s) of challenge: Day 27 - Exposure period: 24 h - Challenge phase (Groups 1 & 2): topical application under occlusive dressing at the following concentrations: 100% & 50%. - Evaluation: 24 and 48 h after challenge
Positive control substance(s):
yes
Remarks:
a-Hexylcinnamaldehyde
Positive control results:
α-Hexylcinnamaldehyde induced skin sensitisation indicating the validity of the study.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100 and 50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100 and 50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 and 50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 and 50%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
None
Remarks on result:
no indication of skin sensitisation

Sensitising potential assessment: 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.

Weight evolution: No abnormality was recorded in the weight growth of both groups.

Mortality: No mortality occurred during this study.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, test substance is not classified as sensitiser according to the criteria of the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In a Magnusson & Kligman maximisation study (GPMT) performed according to OECD Guideline 406 and in compliance with GLP, Guinea pigs were treated as follows:

After induction (intradermic injection at 3.125% and topical application at 100%) of 10 Guinea Pigs of treated group with the test substance and a 17 -day rest phase, the challenge phase, under occlusive dressing for 24 hours, consisted to a single topical application of the test item at 100% and diluted at 50% in paraffin oil. The test concentrations for the main study were determined from a preliminary study.

 

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.

 

The sensitivity of the guinea-pig was checked with known sensitiser i.e., α-Hexylcinnamaldehyde indicating the validity of the study. 

Under the test conditions, test substance is not classified as sensitiser according to the criteria of the annex VI of the Regulation EC No. 1272 /2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for skin sensitisation endpoint.

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

A key study was identified (Phycher, 2006). In this dermal sensitisation study performed according to the OECD guideline No. 406 and in compliance with GLP, the test material was tested in ten Guinea Pigs (5 males and 5 females) using the Magnusson and Kligman method (10 treated animals + 5 controls). The preliminary study determined the concentration to be used for the induction and challenge phases of the main study. The test material diluted in olive oil at 3.125% was administered by injection for intradermal induction. On Day 7, topical induction was performed with the test material as supplied, 24h after brushing with 0.5 mL of sodium lauryl sulfate at 10%. For the challenge, on Day 27, the test material was tested at 50 diluted in paraffin oil and at 100%.

The historical positive control α-Hexylcinnamaldehyde produced skin sensitisation. The test system was therefore considered to be valid.

In both groups, no clinical signs and no deaths were noted during the study. The body weight gain of the treated animals was similar to that of the control animals. After the challenge application, no cutaneous reaction was noted. The overall sensitisation rate was 0%.

Under the test conditions, the test material is not a skin sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Based on the available data no additional self-classification is proposed according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

No data was available for respiratory sensitisation. However, this substance is not a skin sensitizer, therefore according to Figure R.7.3 -2 of the Chapter R.7 (V 4.1 - October 2015) the chemical is not considered as a respiratory sensitizer.