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Diss Factsheets

Administrative data

Description of key information

Guinea pig maximization test (OECD 406); GLP; not skin sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Jul 1996 - Nov 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1992
Deviations:
yes
Remarks:
justification of choice of vehicle not provided, no justification for top dose topical induction and challenge, no use of SLS to induce skin irritation, animal housing conditions slightly divergent
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An in vivo skin sensitisation study was performed after 1 June 2008 for a non-EU regulatory scheme. In accordance with Regulation (EC) No. 1907/2006, the data were included to avoid unnecessary testing.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D Hall Ltd, Burton on Trent, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 5 - 7 weeks
- Weight at study initiation: 345 - 571 g
- Housing: animals held in groups to five in suspended polypropylene cages (six per battery) with open tops, solid floors and stainless steel mesh front panels
- Diet: SQC FD1 (pelleted) diet (Special Diets Services Ltd., Witham, UK), ad libitum
- Water: mains water, ad libitum
- Acclimation period: at least 7 days
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 22
- Humidity (%): 40 - 80
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 10/14
- IN-LIFE DATES: From: 30 Aug 1996 To: 4 Nov 1996
Route:
intradermal and epicutaneous
Vehicle:
other: Alembicol D
Concentration / amount:
intradermal: 1.0%/0.1 mL
epicutaneous: 55%/0.5 mL (= 250 mg test item/animal)
Day(s)/duration:
intradermal: single injection on Day 1, epicutaneous: starting on Day 8, exposure for 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Alembicol D
Concentration / amount:
10% and 20%/0.1 mL
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
20 (controls), 20 (in test groups)
Details on study design:
RANGE FINDING TESTS:
A range finding screening test was done for the intradermal injection phase (induction) and for the topical application phase (induction and challenge) as follows:
1) Intradermal injection phase of induction
Two guinea pigs were used for the incorporation of the test article at a range of 0.1 to 10% m/v in Alembicol D. After 24 h slight erythema were observed in one animal after intraderminal injection of 1, 2.5, 5 and 7.5% (m/v) and in the second animal after injection of 2.5, 5 and 7.5% (m/v) with well defined erythema noted after intradermal injection of 10% (m/v). No dermal reactions were noted 72 h after dermal injection. However, concentrations of 7.5 and 10% (m/v) could not be injected into the model in a manner that was consistent with the test guidelines. Furthermore, it was considered that concentrations of 2.5 and 5% (m/v) together with FCA would not be injectable in the main study. Therefore, the highest injectable concentration was 1%, which was used in the main study.

2) Topical application phase of induction (48 h)
Two guinea pigs were used for the topical application of the test article at a range of 10 to 55% m/m in Alembicol D at least five days after receiving two 0.1 mL intradermal injections of FCA emulsion. 24 h after topical application of the test formulation in a range of 10 to 55% (m/m) one animal showed slight erythema at 25 and 55% and the second animal at 40%. 96 h after topical induction, no dermal reactions were noted. Therefore, the highest concentration of 55% (m/m) was used for the main study.

3) Topical application at challenge (24 h)
Three guinea pigs were used for the topical application of the test article at a range of 5 to 30% m/m in Alembicol D fourteen days after receiving two 0.1 mL intradermal injections of FCA emulsion. 24 h and 48 h after topical application of the test formulation in a concentration range of 5 to 30% (m/m), 1/3 animals showed slight erythema at 30%. No dermal reactions were noted for the other two animals at any concentration or time point investigated. The highest concentration that caused no skin irritation was 20% (m/m) which was used for the main study.
For details, please refer to the attached background material.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: Freund's Complete Adjuvant (FCA) emulsion
Injection 2: 1% m/v test substance in Alembicol D
Injection 3: 1% m/v test substance in FCA emulsion
Epicutaneous: 55% m/m test substance in Alembicol D
- Control group:
Intradermal (3 pairs of injections):
Injection 1: Freund's Complete Adjuvant (FCA) emulsion
Injection 2: Alembicol D
Injection 3: 50% v/v Alembicol D in FCA emulsion
Epicutaneous: Alembicol D
- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: once (each)
- Duration: intradermal induction was performed on Day 1, topical induction was performed on Day 8-10
- Concentrations: intradermal 1%, epicutaneous 55%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (challenge)
- Day(s) of challenge: 22
- Exposure period: 24 h
- Test groups: test substance in Alembicol D and Alembicol D only
- Control group: test substance in Alembicol D and Alembicol D only
- Site: left flank (vehicle) and right flank (test substance)
- Concentrations: 20 and 10%
- Evaluation (hr after challenge): 24 and 48 h after patch removal

OTHER:
Test and control guinea pigs were observed daily for clinical signs of reaction to treatment. The guinea pigs were weighed on Day 1 (day of first induction) and Day 25 (following completion of the challenge phase).
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
yes
Remarks:
20 guinea pigs were treated in a similar manner to the main study animals except for the replacement of 2,4-dinitrochlorobenzene (DNCB, 10 animals) for the test article and the use of corn oil as vehicle (10 animals).
Positive control results:
The following concentrations were used in regards to the positive control DNCB:
intradermal induction: 0.1%
topical induction: 0.5%
first challenge: 0.05 and 0.2%
The dermal reactions after challenge seen in eight of the ten test animals were clearly more marked and more persistent than any control response. For details, please refer to the attached background material.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0% (intradermal) 0% (epicutaneous), challenge: 10% (epicutaneous)
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
slight erythema
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0% (intradermal) 0% (epicutaneous), challenge: 20% (epicutaneous)
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1% (intradermal) 0.5% (epicutaneous), challenge: 0.05% (epicutaneous)
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
slight erythema in 6 animals, well defined erythema in 2 animals with scabbing (multiple foci of eschar) observed in one animal
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1% (intradermal) 0.5% (epicutaneous), challenge: 0.2% (epicutaneous)
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
slight erythema in 4 animals, well defined erythema in 3 animals with scabbing (multiple foci of eschar) observed in 2 animals and moderate erythema in one animal together with scabbing (multiple foci of eschar)
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1% (intradermal) 55% (epicutaneous), challenge: 10% (epicutaneous)
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
slight erythema
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1% (intradermal) 55% (epicutaneous), challenge: 20% (epicutaneous)
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
slight erythema
Remarks on result:
other: scabbing (multiple foci of eschar) in one animal without erythema
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0% (intradermal) 0% (epicutaneous), challenge: 10% (epicutaneous)
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
slight erythema
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0% (intradermal) 0% (epicutaneous), challenge: 20% (epicutaneous)
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1% (intradermal) 0.5% (epicutaneous), challenge: 0.05% (epicutaneous)
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
slight erythema together with desquamation in 3 animals, well defined erythema in one animal and moderate erythema in 2 animals both together with scabbing (multiple foci of eschar)
Remarks on result:
other: desquamation in 2 animals without erythema
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1% (intradermal) 0.5% (epicutaneous), challenge: 0.2% (epicutaneous)
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
slight erythema in 3 animals together with desquamation, well defined erythema in 2 animals together with scabbing in one animal and moderate erythema in 3 animals together with scabbing
Remarks on result:
other: desquamation 2 animals without erythema
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1% (intradermal) 55% (epicutaneous), challenge: 10% (epicutaneous)
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1% (intradermal) 55% (epicutaneous), challenge: 20% (epicutaneous)
No. with + reactions:
0
Total no. in group:
20

General examination in the main study:

No clinical observations of ill health or toxicity were noted during the study for either the main study or positive control groups. Body weight increases, between Day 1 and 25, were recorded for all animals.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 12 72/2008.
Conclusions:
The study is in accordance to OECD TG 406, was conducted under GLP and is considered valid and reliable. Under the conditions chosen, the test substance did not exhibit a skin sensitisation potential. According to criteria of the CLP Regulation (EU) No. 1272/2008, no classification of the test item in regards to skin sensitisation is required.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 Nov - 02 Dec 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1992
Deviations:
yes
Remarks:
justification of choice of vehicle not provided, no justification for top dose topical induction and challenge, no use of SLS to induce skin irritation, temperature of animal housing slightly divergent
GLP compliance:
yes (incl. QA statement)
Remarks:
Ministerium für Arbeit, Gesundheit und Soziales Des Landes Nordrhein-Westfalen, Düsseldorf, Germany
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An in vivo skin sensitisation study was performed after 1 June 2008 for a non-EU regulatory scheme. In accordance with Regulation (EC) No. 1907/2006, the data were included to avoid unnecessary testing.
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratory Animal Breeders, Kißlegg, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 5 - 6 weeks
- Weight at study initiation: 355 - 423 g
- Housing: in groups of two to five per cage (Noryl cages)
- Diet: PROVIMI KLIBA 3420 - Maintenance Diet for Guinea Pigs, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: 08 Nov 2011 To: 02 Dec 2011
Route:
intradermal and epicutaneous
Vehicle:
polyethylene glycol
Concentration / amount:
intradermal: 5.0%/0.1 mL (= 20 mg test item/animal)
epicutaneous: 50%/0.5 mL (= 250 mg test item/animal)
Day(s)/duration:
intradermal: single injection on Day 1, epicutaneous: starting on Day 8, exposure for 48 h
Adequacy of induction:
other: After the first induction the animals in the control group and the test item group showed strong effects up to encrustation at the injection sites
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
50%/0.5 mL (= 250 mg test item/animal)
Day(s)/duration:
24 h
Adequacy of challenge:
not specified
No. of animals per dose:
10 (controls), 20 (in test group)
Details on study design:
RANGE FINDING TESTS
A. INDUCTION EXPOSURE
For intradermal induction: One guinea pig was given intradermal injections two, in each case, with 0.1 mL of the following test item concentrations: 0%, 1%, 2.5% and 5%. The injection sites were evaluated after 24 and 48 h.
For topical induction: Three concentrations (12%, 25% and 50%) and the vehicle were tested on four guinea pigs. The patches moistened with 0.5 mL of the test item formulations or the vehicle were applied to each animal under occlusive conditions for 24 h. At the end of the exposure period, the remaining test item was removed with physiological saline. No later than 21 h after removing the patches the treated areas were shorn in the zone of the challenge area. The skin reactions were evaluated 48 h and 72 h after the start of the application. No skin reactions were recorded both 48 h and 72 h after topical application of the test formulations (0-50%).

B. CHALLENGE EXPOSURE
One week prior to the challenge, the challenge concentration was determined on 2 guinea pigs in the main study which were treated in the same manner as the control animals during the inductions. Four patches each loaded with 0.5 mL test item formulations (12%, 25% and 50%) or the vehicle were applied to each animal under occlusive conditions for 24 h. At the end of the exposure period, the remaining test item was removed with physiological saline. No later than 21 h after removing the patches the treated areas were shorn in the zone of the challenge area. The skin reactions were evaluated 48 and 72 h after start of the application. No skin reactions were recorded both 48 h and 72 h after application of the test formulations (0-50%). Based on these results, the following concentrations were selected for the main study: Intradermal induction: 5%, topical induction: 50% and challenge: 50%. For details on the results, please refer to the attached background material.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) Freund's Complete Adjuvant (FCA)/sterile physicological saline solution
Injection 2: 5% test substance in polyethylene glycol 400
Injection 3: 5% test substance in a 1:1 mixture of (v/v) FCA/polyethylene glycol 400
Epicutaneous: 50% test substance in polyethylene glycol 400
- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/sterile physicological saline solution
Injection 2: polyethylene glycol 400
Injection 3: polyethylene glycol 400 in a 1:1 mixture (v/v) FCA
Epicutaneous: polyethylene glycol 400
- Site: dorsal region (intradermal + epicutaneous)
- Frequency of applications: once (each)
- Duration: intradermal induction was performed on Day 1, topical induction was performed on Day 8-10
- Concentrations: intradermal 5%, epicutaneous 50%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (challenge)
- Day(s) of challenge: challenge was performed three weeks after intradermal induction on Day 22
- Exposure period: 24 h
- Test groups: test substance and vehicle only
- Control group: test substance and vehicle only
- Site: right flank (test substance caudal, vehicle cranial)
- Concentrations: 50%
- Evaluation (hr after challenge): 48 and 72 h

OTHER:
The animals were observed for clinical signs at least once daily throughout the entire study period. Body weights were recorded on Day1 before the first induction and at the end of the study.
Challenge controls:
The control group is actually a challenge control
Positive control substance(s):
yes
Remarks:
The GPMT was checked for reliability in a separate study with female guinea pigs using alpha hexyl cinnamic aldehyde formulated in polyethylen glycol 400.
Positive control results:
The following concentrations were used in regards to the positive control alpha hexyl cinnamic aldehyde (HCA) in a reliability test:
intradermal induction: 5%
topical induction: 25%
first challenge: 12%
second challenge: 6%

After the first challenge 100% of the test item animals and 60% of the control animals exhibited dermal reactions in the challenge treatment and after the second challenge 60% of the test item animals. There was no reddening of the skin to be observed in control group animals.
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0% (intradermal) 0% (epicutaneous), challenge: 50% (epicutaneous)
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5% (intradermal) 50% (epicutaneous), challenge: 50% (epicutaneous)
No. with + reactions:
0
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0% (intradermal) 0% (epicutaneous), challenge: 50% (epicutaneous)
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
5% (intradermal) 50% (epicutaneous), challenge: 50% (epicutaneous)
No. with + reactions:
0
Total no. in group:
20
Key result
Group:
positive control
Dose level:
5% (intradermal), 25% (topical induction), first challenge: 12%, second challenge: 6%
Remarks on result:
other: reliability study: 60% of the HCA-treated animals exhibited dermal reactions after the second challenge

General examination:

Appearance and behaviour of the test item group were not different from the control group.
At the end of the study, the mean body weight of the treatment group animals was in the same range than that of the control group animals.

After the intradermal induction, the animals in the control group showed after 48 hours:
• red wheal
• white wheal with red surrounding

The animals in the test item group showed after 48 hours:
• red wheal
• white wheal with red surrounding
• encrustation

At Day 8, encrustation was recorded at the injection sites in the control group and wheals and encrustation in the test item group.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 12 72/2008.
Conclusions:
The study is in accordance to OECD TG 406, was conducted under GLP and is considered valid and reliable. Under the conditions chosen, the test substance did not exhibit a skin sensitisation potential. According to criteria of the CLP Regulation (EU) No. 1272/2008, no classification of the test item in regards to skin sensitisation is required.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

To evaluate skin sensitising properties of the test substance, data on two skin sensitisation studies according to or similar to OECD guideline 406 are available.

 

In the key study, skin sensitising properties of the test substance were evaluated in guinea pigs similar to the Guinea Pig Maximization Test (OECD 406) in compliance with GLP (M-424556-01-2). The highest concentrations tested in a dose-range finding test were selected for the main study: 5 and 50% (w/w) were chosen for intradermal and epicutaneous induction, respectively, and 50% for the challenge phase. No skin irritation was noted at the highest concentration tested. The test group comprised 20 female Hartley guinea pigs. A control group of 10 female animals was included in the study. On Day 1, 3 pairs of intradermal injections were made in the interscapular region of all animals:

  • Freund's complete adjuvant (FCA) diluted 1:1 with sterile physiological saline (both groups),
  • test substance at a concentration of 5% in polyethylene glycol 400 (treated group) or vehicle alone (control group),
  • 5% test substance in an equal mixture of FCA/ polyethylene glycol 400 (treated group) or in a 1:1 mixture of FCA/ polyethylene glycol 400 (control group).

One week after the intradermal induction, the test areas of the animals were shorn. The test sites were then topically treated with either the test item (50%) or the vehicle alone (0.5 mL polyethylene glycol 400). After a 48-h exposure period, the remaining test substance was removed with sterile physiological saline. The challenge was performed three weeks after the intradermal induction on Day 22. The test sites of the animals were shorn and 50% of the test substance paste was placed on the right flank (caudal) of the animal for 24 h. A patch loaded with 0.5 mL vehicle only was also placed on the right flank (crania) as control. At the end of the exposure period, the remaining test substance was removed with physiological saline. After the first induction, control animals and animals treated with the test substance showed strong effects, including red wheals, white wheals and encrustation at the injections sites. No skin irritation was noted at the test site following the topical induction. No skin effects were observed 48 and 72 h after the challenge with 50% test substance, neither in in the control nor in the tested animals. No clinical signs were recorded until the end of the observation period and body weight gain was comparable among the groups. A concurrent positive control group together with a vehicle control group was similarly treated as described above except for the replacement of alpha hexyl cinnamic aldehyde (HCA) for the test article. HCA caused a 100% positive response in the positive control animals after the first challenge, while 60% of the vehicle control animals showed skin irritation effects. After the second challenge 60% of the HCA-treated animals exhibited dermal reactions and none of the vehicle control animals. The sensitivity as well as the reliability of the experimental technique is thus confirmed by this study. Taken together, the test substance did not induce skin sensitisation in guinea pigs under the experimental conditions chosen.

A second study also investigated the potential of the test item to cause skin sensitisation similar to OECD guideline 406 in compliance with GLP (supporting study M-027406-01-1). The test group comprised 20 female Dunkin-Hartley guinea pigs. 20 female guinea pigs were included in the control group. Concentrations used for induction and challenge were based on the results of a range-finding test. The concentrations did not cause mild irritation, but were the maximum concentrations technically possible. On Day 1, 3 pairs of intradermal injections were made in the interscapular region of all animals:

  • Freund's complete adjuvant (FCA) emulsion (both groups),
  • test substance at a concentration of 1% (m/v) in Alembicol D (treated group) or vehicle alone (control group),
  • 1% test substance in FCA emulsion (treated group) or in a 1:1 mixture of FCA/ Alembicol D (control group).

On Day 7, the test areas were clipped and on Day 8 0.5 mL of 55% (m/m) test substance in Alembicol D or vehicle alone (control group) were applied on the previously shaved test areas. An occlusive dressing held the patches in place for 48 h. On Day 21, both flanks of the animals were clipped and subsequently shaved on Day 22. On the same day, 12 mm Finn chamber loaded with approximately 0.1 mL vehicle were applied to the left flank of the animals . Finn chambers containing the test formulation for challenge (10 or 20% (m/m) in Alembicol D) were applied to the right flank of each animal. The chambers were removed after the exposure period of 24 h. The treated areas of skin were washed with arachis oil. Dermal responses were assessed 24 and 48 h after removal of the chamber. After intradermal injection, slight or well-defined erythema were noted for the test and control animals. No erythema was apparent in the test group after topical induction with 55% of the test item. However, slight to well-defined erythema was observed in the control animals. After challenge with 20% test item, 3/20 treated animals showed slight erythema after 24 h and no skin reaction was apparent after 48 h. After challenge with 10% test item, 2/20 treated animals showed slight erythema after 24 h and no skin reaction was apparent after 48 h. Slight erythema was also observed in the control animals after challenge with 10% of the test item in 1/20 animals after 24 h and in 1/20 control animals after 48 h. However, the dermal reactions seen in the test animals were not clearly stronger than those in the control group. Furthermore, no clinical observations of ill health or toxicity were noted during the study for either the main study or positive control groups. All animals gained body weight between Day 1 and 25. A concurrent positive control group of 10 female guinea pigs together with a respective vehicle control group (10 animals) were treated according to the same protocol as described above with 2,4-dinitrochlorobenzene (DNCB) and corn oil, respectively. The concentration used for the positive control were as follows: 0.1% m/v DNCB in corn oil and/or adjuvant for intradermal injection, 0.5% m/v DNCB in corn oil for topical induction and 0.2 and 0.05% m/v DNCB in corn oil for challenge application. DNCB caused a positive response in 8/10 test animals following the challenge application. This is indicative for skin sensitization and confirmed the sensitivity of the test model. Taken together, the test substance did not induce skin sensitisation in guinea pigs under the experimental conditions chosen.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The studies were performed according to GLP and are considered valid and reliable. Under the conditions tested, the test item did not induce skin sensitization in guinea pigs. Therefore, CLP/EU GHS criteria are not met and no classification is required according to Regulation (EC) No 1272/2008.