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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP study.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 407-470 g (males), 380-466 g (females)
- Housing: Macrolon Type III cages with softwood granules, Type T, coarse I bedding (Fa H. Buntenback, D-5660, Solingen 11. One animal per cage.
- Diet (e.g. ad libitum): Standard experimental animal feed ad libitum, ssniff (G) individual diet, Fa. Ssniff Spezialfutter GmbH.
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 8 days under test conditions prior to substance application. Veterinarian observation of animals before the test start.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 55 +/- 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
- From: 12 November 1985
- To: 6 December 1985.
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Concentration / amount:
0.1 % via intradermal injection and a paste of 50 % (1 g/animal) during the induction phase. 25 % in challenge (provocation) phase.
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
0.1 % via intradermal injection and a paste of 50 % (1 g/animal) during the induction phase. 25 % in challenge (provocation) phase.
No. of animals per dose:
1 dose, 20 animals per dose. 20 animals in a control group.
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 6 intradermal (2 x test substance solution, 2 x test substance solution/FCA (1:1), 2x FCA/physiological saline (1:1) + 2 day epicutaneous exposure.
- Exposure period: 8 days
- Test groups: 1
- Control group: 1
- Site: shoulder region, 6-8 cm region shaved prior.
- Frequency of applications: 1 daily for 6 days, intradermal, starting on the first research day, then 1 epidermal on the 8th research day
- Duration: 8 days total
- Concentrations: Intradermal: 0.1 % in physiological saline (0.9 % NaCl), with Freunds complete adjuvant (FCA, Difco Laboratories, Detroit, MI, USA). Epicutaneous: (48 h exposure via occlusive patch (Acrylastic, P, Beiersdorft and Co. AG, D-2000 Hamburg), on filter paper with plastic foil (2 x 4 cm), 1 g in 0.5 mL in physiologic saline
- Control: same treatment, however only the vehicle was applied rather than the test material.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on research day 22
- Exposure period:: 24 h
- Test groups: 1
- Control group: same treatment as the animals in the test substance group
- Site: left flank for test substance, right flank for control. Flanks were shaved on the 22nd research day (approximately 5 x 5 cm)
- Concentrations:50 %, 50 mg/animal in physiological saline
- Evaluation (hr after challenge): 24 and 48 hours after removal of patch (Leukotest), on the 24th and 25th research days.

RANGE-FINDING STUDIES:
The maximum non-irritating concentrations for the intradermal and epidermal applications in the induction phase, as well as the non-irritating concentrations for the epidermal application in the provocation phase were determined in pilot tests on 2-3 guinea pigs respectively.
Challenge controls:
A challenge control group was included (see details on study design).
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
weak erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: weak erythema.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.1% induction, 25% challenge
No. with + reactions:
9
Total no. in group:
20
Clinical observations:
weak to mild erythema
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1% induction, 25% challenge. No with. + reactions: 9.0. Total no. in groups: 20.0. Clinical observations: weak to mild erythema.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
weak erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: weak erythema .
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.1% induction, 25% challenge
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
weak to mild erythema
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1% induction, 25% challenge. No with. + reactions: 7.0. Total no. in groups: 20.0. Clinical observations: weak to mild erythema .

Two of the control animals displayed weak erythema or edema at 24 and 48 h. Nine animals in the test group displayed weak to mild erythema, and this persisted in 7 of the 9 animals at 48 h. There was no systemic toxicity noted. Statistical analysis indicated that the incidence of positive skin reactions after nicotinamide exposure was not significant (p < 0.01).

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The sensitisation potential of the test material was assessed in a guinea pig maximisation test. Nine of the twenty animals exposed displayed weak signs of erythema at 24 h, 7 of which persisted for 48 h, while two animals in the control group displayed erythema. This was determined to be non-significant in a statistical analysis. The test item is determined to be non-sensitising.
Executive summary:

A study was carried out according to OECD Guideline 406 (Skin Sensitisation). The sensitisation potential of the test material was assessed in a guinea pig maximisation test. Twenty Pirbright White guinea pigs were intradermally administered the test substance with and without adjuvant, followed by one 48 h epidermal exposure to the test substance under an occlusive patch. After 3 weeks the animals were challenged with an epidermal patch of 50 % test material (50 mg) under an occlusive wrap for 24 h. Nine of the twenty animals exposed displayed weak signs of erythema at 24 h, 7 of which persisted for 48 h, while two animals in the control group displayed erythema. This was determined to be non-significant in a statistical analysis. The test item is determined to be non-sensitising.

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

Key study - Guinea pig maximisation test

A study was carried out according to OECD Guideline 406 (Skin Sensitisation). The sensitisation potential of the test material was assessed in a guinea pig maximisation test. Twenty Pirbright White guinea pigs were intradermally administered the test substance with and without adjuvant, followed by one 48 h epidermal exposure to the test substance under an occlusive patch. After 3 weeks the animals were challenged with an epidermal patch of 50 % test material (50 mg) under an occlusive wrap for 24 h. Nine of the twenty animals exposed displayed weak signs of erythema at 24 h, 7 of which persisted for 48 h, while two animals in the control group displayed erythema. This was determined to be non-significant in a statistical analysis. The test item is determined to be non-sensitising.

Supporting study – Buehler test

A study was carried out according to OECD Guideline 406 (Skin Sensitisation). Ten Pirbright White guinea pigs were epidermally administered a 50 % dilution of a 5 % aqueous solution of test substance for 3 days, 6 hours per day, on days 1, 8 and 15, under an occlusive patch. This was followed on day 30 by one 6 h epidermal exposure to the test substance under the same conditions. Five control animals received physiological saline in the same procedure. Skin reactions were assessed at 24 and 48 h after patch removal using a scale of 0 to 4 to rank erythema and edema. None of the animals exposed to the test item displayed signs of sensitisation. The test item is concluded to be non-sensitising in the Buehler test.


Migrated from Short description of key information:
Two studies were carried out according to OECD Guideline 406 (Skin Sensitisation). In the key study sensitisation potential of the test material was assessed in a guinea pig maximisation test. In the supporting study the sensitisation potential was determined according to the Buehler test. Both studies determined the test item to be non-sensitizing.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the data available the substance is not classified and labeled according to Regulation 1272/2008/EEC (CLP) and Directive 67/548/EEC (DSD).