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Description of key information

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:
11 September 2000 - 16 October 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
(adopted 1992)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The present in vivo study was conducted in the year 2001. In vivo skin sensitisation studies that were carried out or initiated before 10 May 2017, and that meet the requirements set out in Article 13(3), first subparagraph, and Article 13(4) shall be considered appropriate to address the standard information requirement.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Darley Oaks, Newchurch, Burton-on-Trent, Staffordshire
- Age at study initiation: young adult (less than one year old)
- Weight at study initiation: 354-440 g
- Housing: 2 per cage (dose ranging study), 5 per cage (main study)
- Diet: Guinea Pig Diet FD1, supplied by Special Diets Services Ltd, 1 Stepfield, Witham, Essex, CM8 3AD, ad libitum. Each cage was also offered a supplement of hay and organically grown cabbage approximately twice weekly.
- Water: domestic mains quality water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-20
- Humidity (%): 55 ± 15
- Air changes (per hr): at least 15
- Photoperiod: 12 hrs dark / 12 hrs light
Route:
intradermal and epicutaneous
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5%
Concentration / amount:
Main study:
-Intradermal induction: 15% test substance
-Topical induction: 40% test substance
-Challenge: 40% test substance
Route:
epicutaneous, occlusive
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5%
Concentration / amount:
Main study:
-Intradermal induction: 15% test substance
-Topical induction: 40% test substance
-Challenge: 40% test substance
No. of animals per dose:
Dose ranging study: 2 animals for each intradermal induction, topical induction, and challenge procedure
Main study:
-Control group: 5 animals
-Test group: 10 animals
Details on study design:
RANGE FINDING TESTS:
Dose ranging for induction:
Intradermal induction: 0.1 mL of a 1, 5, 15, 30% solution of the test substance
Topical applications: 0.1 mL of a 5, 15, 30, 40% solution of the test substance

Dose ranging for challenge:
Intradermal induction: 0.1 mL of a 50% aqueous FCA, 0.5% CMC (vehicle), vehicle/50% aqueous FCA
Topical induction:
6 days after induction: 0.5 mL of a 10% SLS solution, one day later 0.5 mL of a 0.5% CMC solution

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: intradermal and topical
- Exposure period: intradermal injections, topical induction for 48 h
- Test group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: 30% test substance solution in vehicle (1:1)
Injection 3: 30% test substance solution in 50% FCA (1:1)
Final concentration of test article was therefore 15%.
Topical application: 40% test substance solution
1 day prior to treatment the clipped area was treated with 0.5 ml of 10% sodium lauryl sulphate (SLS).
- Control group: same procedure as test group but without test material
- Site: area across the scapular region
- Frequency of applications: day 0 (intradermal induction), day 8 (topical challenge)
- Duration: topical application: 24 h

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 13 days after topical induction.
- Exposure period: 24 h
- Test groups: test substance and vehicle
- Control group: test substance and vehicle
- Site: flanks of the animal
- Concentrations: 40%
- Evaluation (hr after challenge): 24 and 48 h
Challenge controls:
The control group is actually a challenge control.
Positive control results:
The sensitivity of the Dunkin-Hartley strain of guinea pig to a mild to moderate sensitizer, 2-mercaptobenzothiazole (MBT), is checked at 6 month intervals. In the most recent positive control test MBT was administered at induction at concentrations of 5% (injection) and 25% (topical) w/v in maize oil. Challenge was carried out at a concentration of 25% MBT in maize oil.
Results:
Vehicle control: 0/10 animals showed a positive reaction.
Positive control: 20/20 animals showed a positive reaction.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0% induction, 40% epicutaneous challenge
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0% induction, 40% epicutaneous challenge. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0% induction, 40% epicutaneous challenge
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0% induction, 40% epicutaneous challenge. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
15% intradermal induction, 40% epicutaneous challenge
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 15% intradermal induction, 40% epicutaneous challenge. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
15% intradermal induction, 40% epicutaneous challenge
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 15% intradermal induction, 40% epicutaneous challenge. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
other: The sensitivity of the Dunkin-Hartley strain of guinea pig to a mild to moderate sensitizer, 2-mercaptobenzothiazole (MBT), is checked at 6 month intervals.
Group:
positive control
Dose level:
concentrations of 5% (injection) and 25% (topical) w/v in maize oil
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Based on the result of this study, the test article is not considered a skin sensitizer in guinea pigs.
Executive summary:

The delayed contact hypersensitivity of the test material was investigated by means of a Magnusson-Kligman Maximization Test in guinea pigs following OECD guideline 406. The Magnusson-Kligman Maximization Test comprises 2 procedures: an induction and a challenge procedure. The induction procedure consisted of exposure to the test material via 2 routes, intradermal injection and topical application. The animals were also exposed to an adjuvant material via intradermal injection. This was followed by a challenge exposure to the test material via topical application. Two groups of animals were used in the study, a Test and a Control Group. The Test Group contained 10 animals and the Control Group contained 5. During the induction procedure, the Test Group was exposed to 15% test material via intradermal injection and 40% test material via topical application (the maximum practicable concentration). The Control Group was exposed to vehicle, 0.5% carboxymethylcellulose (CMC), only during this procedure. Following challenge with 40% test material, no positive responses were noted in any of the Test or Control Group animals. Based on the results of this study and under the conditions chosen, the test article is considered not to be a sensitizer in guinea pigs.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
Migrated from Short description of key information:
Based on the result of Magnusson-Kligman Maximisation Test in Guinea Pigs, the substance is not considered a skin sensitizer in guinea pigs.

Justification for selection of skin sensitisation endpoint:
key study

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

No positive responses were noted in any of the Test or Control Group animals of the skin sensitisation test according to OECD 406.

According to the criteria of Regulation (EC) No.: 1272/2008, the substance is not classified as skin or respiratory sensitizer. Also, according to the criteria specified by Directive 67/548/EEC the substance is not classified with regard sensitisation.

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