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Toxicological information

Skin sensitisation

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Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material: Nicotinamide

In vivo test system

Test animals

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.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
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.
Challengeopen allclose all
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

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
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 .

Any other information on results incl. tables

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).

Applicant's summary and conclusion

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.