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Skin sensitisation

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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: adequat conducted study according to current guidelines under GLP with good documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
A Buehler test was conducted as this study was required for registration purpose outside of the REACH legislation and thus to avoid additional animal testing in the LLNA.
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: 234g and 275g
- Housing: housed in groups of 2 in polycarbonate containers. The flooring of the cages was covered with dust-free wood shavings and the top fitted a stainless steel lid containing with a feeding device and drinking device of 500 mL
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum acclimatization period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° C ± 3° C
- Humidity (%):from 30 % to 70 %,
- Air changes (per hr):at least 10 cycles per hour
- Photoperiod (hrs dark / hrs light):12 hrs day / 12 hrs darkness
Route:
epicutaneous, occlusive
Vehicle:
other: unchanged or diluted with liquid paraffin
Concentration / amount:
Induction phase: 100% test item
1st Challenge: 50% test item (maximal non irritant concentration)
2st Challenge: 10% test item
Route:
epicutaneous, occlusive
Vehicle:
other: unchanged or diluted with liquid paraffin
Concentration / amount:
Induction phase: 100% test item
1st Challenge: 50% test item (maximal non irritant concentration)
2st Challenge: 10% test item
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: Maximum Non Irritant Concentration (M.N.I.C.) determination, Three guinea pigs were treated with the test item placed onto the selected treatment sites and covered with an occlusive dressing (25mm x 25mm gauze patches hydrophilic Codex of 8-layer Gazin® from
Lohmann & Rauscher held in contact with the skin by means of 50 mm wide hypoallergenic micropore™ adhesive tape from 3M and Blenderm™ from 3M) for a period of 6 hours at 4 different concentrations: 100% diluted at 75% (v/v), 50% (v/v) and 25% (v/v) in liquid paraffin.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 local applications were performed at D0, D6 and D13 during 6 hours under occlusive dressing (25mm x 25mm gauze patches hydrophilic Codex of 8-layer Gazin
- Exposure period:6h
- Test groups: yes, treated group received 0.5 mL of the test item at 100%, third induction with 75% testitem diluted in liquid paraffin.
- Control group: liquid paraffin
- Frequency of applications:D0, D6 and D13
- Duration: 14d + 14d rest phase
- Concentrations: 100% and 75%

1st CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6h
- Test groups: 0.5 mL of the test item at 50% (v/v) (MNIC = maximal non irritant concentration) diluted in liquid paraffin
- Control group:liquid paraffin
- Concentrations: 50%
- Evaluation (hr after challenge): 24h, 48h, 72h

2st CHALLENGE EXPOSURE
- No. of exposures: 1
- Exposure period: 6h
- Test groups: 0.5 mL of the test item at 10% diluted in liquid paraffin
- Control group: liquid paraffin
- Concentrations: 10%
- Evaluation (hr after challenge): 24h, 48h, 72h
Positive control substance(s):
yes
Remarks:
α-Hexylcinnamaldehyde
Positive control results:
The results of the 3 last positive groups (Reference substance: α-Hexylcinnamaldehyde CAS n°
101-86-0 - Tests n°12-14) carried out as method sensibility, are presented in appendix 2 (Attached background material).
Reading:
other: positive control
Group:
positive control
Remarks on result:
other: The results of the 3 last positive groups (Reference substance: α-Hexylcinnamaldehyde CAS n° 101-86-0 - Tests n°12-14) carried out as method sensibility, are presented in appendix 2 (Attached background material).
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: other: 1 st challenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 50%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: slight to moderate erythema.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: other: 1 st Challenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 50%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: slight to moderate erythema.
Reading:
1st reading
Hours after challenge:
72
Group:
negative control
Dose level:
50%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: other: 1st challenge. . Hours after challenge: 72.0. Group: negative control. Dose level: 50%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: slight to moderate erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: other: 1 st challenge. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: slight to moderate erythema.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: other: 1 st challenge. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: slight to moderate erythema.
Reading:
1st reading
Hours after challenge:
72
Group:
test chemical
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: other: 1st challenge. . Hours after challenge: 72.0. Group: test group. Dose level: 50%. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: slight to moderate erythema.
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: other: 2nd challenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: other: 2nd challenge. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: slight to moderate erythema.
Reading:
rechallenge
Hours after challenge:
72
Group:
negative control
Dose level:
10%
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: other: 2nd challenge. . Hours after challenge: 72.0. Group: negative control. Dose level: 10%. No with. + reactions: 3.0. Total no. in groups: 10.0. Clinical observations: slight to moderate erythema.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: other: 2nd challenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
slight erythema
Remarks on result:
other: Reading: other: 2nd challenge. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 4.0. Total no. in groups: 20.0. Clinical observations: slight erythema.
Reading:
rechallenge
Hours after challenge:
72
Group:
test chemical
Dose level:
10%
No. with + reactions:
6
Total no. in group:
20
Clinical observations:
slight to moderate erythema
Remarks on result:
other: Reading: other: 2nd challenge. . Hours after challenge: 72.0. Group: test group. Dose level: 10%. No with. + reactions: 6.0. Total no. in groups: 20.0. Clinical observations: slight to moderate erythema.

Maximal Non Irritant Concentration MNIC 50%

Interpretation of results:
GHS criteria not met
Conclusions:
In conclusion, in view of these results, under these experimental conditions, the test item Amines, tri- C8-10-alkyl must not be classified as a skin sensitiser.
Executive summary:

The aim of the study was to evaluate the possible allergenic activity of the test item Amines, tri-C8- 10-alkyl after topical administration in guinea pigs (BASF SE, 2013, 32H0674/12X410) . After induction of 20 guinea pigs by 3 topical applications with the test item Amines, tri-C8-10-alkyl applied as supplied (100%) for the inductions No.1 & No.2 and diluted at 75% in liquid paraffin for the induction No.3 under occlusive dressing and a 13-day rest phase, the challenge phase, under occlusive dressing for 6 hours, consisted a single topical application of the test item diluted at 50% in liquid paraffin and of a negative control (liquid paraffin). The experimental protocol was established from the O.E.C.D. guideline n°406 dated July 17th, 1992, and the method B.6 of the Council regulation No. 440/2008. In the treatment group (treatment dose of 50%), it was recorded a slight to moderate erythema in 100% (20/20) of the animals from the treated group, 24, 48 and 72 hours after the challenge phase, on the treated area. A slight to moderate oedema was noted in 65% (13/20), in 55% (11/20) and in 50% (10/20) of the animals from the treated group, 24, 48 and 72 hours respectively after the challenge phase, on the treated area. In the control group (associated with the treatment dose of 50%), it was recorded a slight to moderate erythema in 100% (10/10), of the animals from the treated group, 24, 48 and 72 hours after the challenge phase, on the treated area. A slight oedema was noted in 70% (7/10), in 60% (6/10) and in 60% (6/10) of the animals from the treated group, 24, 48 and 72 hours respectively after the challenge phase, on the treated area. In the treatment group (liquid paraffin), no cutaneous reaction attributable to allergy was recorded in animals from the treated group after the challenge phase, on the control area. In the control group, no cutaneous reaction attributable to allergy was recorded in animals from the control group after the challenge phase, on the control area. In view to confirm or infirm these results, a new challenge phase was performed with the test item diluted at 10% in liquid paraffin and with liquid paraffin as control (vehicle), after a rest phase of 6 days. In the treatment group (treatment dose of 10%), it was recorded a slight to moderate erythema in 20% (4/20) and 30% (6/20) of the animals from the treated group, 48 and 72 hours after the challenge phase, on the treated area respectively. In the control group (associated with the treatment dose of 10%), it was recorded a slight to moderate erythema in 30% (3/10), of the animals from the treated group, 48 and 72 hours after the challenge phase, on the treated area. Only reactions in the test group animals that exceeded the most severe reactions seen in the control group animals were attributed to skin sensitization. So, no sensitization reaction was noted in animals from the treated group, 24, 48 and 72 hours after the challenge phase, on the area challenged with the test item at 10%. No cutaneous reaction was recorded in animals from the treated and control groups after the challenge phase, on the treated area with liquid paraffin (vehicle). In conclusion, in view of these results, under these experimental conditions, the test item Amines, tri- C8-10-alkyl must not be classified as a skin sensitiser, 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

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

There are valid study data available to assess the sensitising potential Amines, tri-C8- 10-alkyl. No valid information for Amines, tri-C8- 10-alkyl on respiratory sensitisation is available.

Guideline conform studies:

The possible allergenic activity of the test item Amines, tri-C8- 10-alkyl after topical administration in guinea pigs was investigated according to OECD 406 (Bühler) (BASF SE, 2013, 32H0674/12X410) . After induction of 20 guinea pigs by 3 topical applications with the test item Amines, tri-C8-10-alkyl applied as supplied (100%) for the inductions No.1 & No.2 and diluted at 75% in liquid paraffin for the induction No.3 under occlusive dressing and a 13-day rest phase, the challenge phase, under occlusive dressing for 6 hours, consisted a single topical application of the test item diluted at 50% in liquid paraffin and of a negative control (liquid paraffin). The experimental protocol was established from the O.E.C.D. guideline n°406 dated July 17th, 1992, and the method B.6 of the Council regulation No. 440/2008. In the treatment group (treatment dose of 50%), it was recorded a slight to moderate erythema in 100% (20/20) of the animals from the treated group, 24, 48 and 72 hours after the challenge phase, on the treated area. A slight to moderate oedema was noted in 65% (13/20), in 55% (11/20) and in 50% (10/20) of the animals from the treated group, 24, 48 and 72 hours respectively after the challenge phase, on the treated area. In the control group (associated with the treatment dose of 50%), it was recorded a slight to moderate erythema in 100% (10/10), of the animals from the treated group, 24, 48 and 72 hours after the challenge phase, on the treated area. A slight oedema was noted in 70% (7/10), in 60% (6/10) and in 60% (6/10) of the animals from the treated group, 24, 48 and 72 hours respectively after the challenge phase, on the treated area. In the treatment group (liquid paraffin), no cutaneous reaction attributable to allergy was recorded in animals from the treated group after the challenge phase, on the control area. In the control group, no cutaneous reaction attributable to allergy was recorded in animals from the control group after the challenge phase, on the control area. In view to confirm or infirm these results, a new challenge phase was performed with the test item diluted at 10% in liquid paraffin and with liquid paraffin as control (vehicle), after a rest phase of 6 days. In the treatment group (treatment dose of 10%), it was recorded a slight to moderate erythema in 20% (4/20) and 30% (6/20) of the animals from the treated group, 48 and 72 hours after the challenge phase, on the treated area respectively. In the control group (associated with the treatment dose of 10%), it was recorded a slight to moderate erythema in 30% (3/10), of the animals from the treated group, 48 and 72 hours after the challenge phase, on the treated area. Only reactions in the test group animals that exceeded the most severe reactions seen in the control group animals were attributed to skin sensitization. So, no sensitization reaction was noted in animals from the treated group, 24, 48 and 72 hours after the challenge phase, on the area challenged with the test item at 10%. No cutaneous reaction was recorded in animals from the treated and control groups after the challenge phase, on the treated area with liquid paraffin (vehicle). In conclusion, in view of these results, under these experimental conditions, the test item Amines, tri- C8-10-alkyl must not be classified as a skin sensitiser, 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

Key study assignment:

As there a only one reliable and relevant study investigating the dermal sensitisation of Amines, tri- C8-10-alkyl this study is integrated as key study.

 

Skin sensitisation assessment:

The only available study for skin sensitisation indication no skin sensitising effect based on a guinea pig (Bühler) test. Therefore the substance is expected to be not skin sensitising.


Migrated from Short description of key information:
Skin sensitisation:
- in vivo skin sensitisation, guinea pig, Bühler, OECD 406: negative for skin sensitisation (slight delayed irritations in test and control group) (BASF SE, 2013, 32H0674/12X410)

Justification for selection of skin sensitisation endpoint:
most reliable and relevant study available

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Migrated from Short description of key information:
Respiratory sensitisation:
- No data available

Justification for classification or non-classification

According to GHS and DSD substances shall be classified as skin sensitiser if there are positive results from appropriate animal test. As there are no positive results from a animal the substance is considered to be not sensitising it needs not to be classified according to GHS (Regulation (EU) 1272/2008) as sensitising to skin and also not to be classified according to DPD (67/548/EEC).

 

Labelling for sensitisation:

GHS: no label

DSD: no label

 

Respiratory sensitisation:

No data available