Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

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

Test animals

Species:
rabbit
Strain:
other: White Russian (albino)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Males 14 - 16 months; Females 9 - 15 months
- Weight at study initiation: Males 2.38 - 2.95 kg; Females 2.48 - 2.93 kg
- Fasting period before study: 16 hours before treatment
- Housing: Stainless steel cages with grating floor, type ASTA, size: 48.5x40x36.5 cm (LxBxH), supplied by ASTA Pharma AG, 0-4800 Bielefeld, Germany
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: The animals were kept at least 5 days under test conditions before substance application after hair clipping. Veterinary supervision of the animals was done before start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 - 22.5
- Humidity (%): 40 - 70 for a short period down to 35 %; this deviation was without any influence on the results of the study
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 6 a.m. to 6 p.m. artificial lighting, 6 p.m. - 6 a.m. natural light-dark-rhythm

IN-LIFE DATES:
- From: 14 Aug. 1990
- To: 29 Aug. 1990

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Shorn skin between shoulder and sacral region
- % coverage: 100 %
- Type of wrap if used: Occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washing with tapwater
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
Males 2000 mg/kg bw; Females 2000 mg/kg bw
No. of animals per sex per dose:
5 Males; 5 Females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were continuously observed for the first 4 to 6 hours after application and then once daily. The nature of the toxicity as well as the onset, the intensity, and the duration of the signs were recorded. Mortality was checked twice daily (a.m. and p.m.), on Saturdays, Sundays, on national and business holidays only once daily. The body weights were recorded at the beginning and also 7 and 14 days after application.
- Necropsy of survivors performed: A gross necropsy was performed on all animals. Macroscopical examination included external appearance, body orifices, body cavities (thoracic and abdominal), and their contents.
Statistics:
Not applicable.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
The only sign of toxicity was a slight reddening of the application site detected immediately after removal of the patches. The finding was present in some animals up to the end of the observation period. Clinical symptoms are shown in table 1.
Body weight:
The individual body weights are listed in table 3.
Gross pathology:
At necropsy no abnormal findings, except the a.m. slight reddening at the application site, were recorded.

Any other information on results incl. tables

Table 1: Male animal clinical symptoms

Dose  Symptoms No. Animals
2000 mg/kg bw Slight reddening of the application site 5/5

Table 2: Female animals clinical symptoms

Dose  Symptoms No. Animals
2000 mg/kg bw Slight reddening of the application site 5/5

Table 3: Male and female body weights

Dose (mg/kg bw)  Dermal Animal No.  Day 0  Day 7  Day 14 

Male Animals 

Body weights (kg)
2000 2203 2.44 2.45 2.45
2215 2.56 2.56 2.56
2205 2.38 2.34 2.34
2217 2.47 2.47 2.47
2263 2.95 2.89 2.89
Female Animals 
2000 2286 2.48 2.5 2.5
2294 2.49 2.47 2.47
2288 2.86 2.84 2.89
2290 2.54 2.55 2.51
2238 2.93 2.94 2.96

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Nicotinamide was tested for acute toxicity after single dermal application to rabbits. The LD50 values for male as well as female rabbits were above 2000 mg/kg bw (limit test).
Executive summary:

A study according to EU Method B.3 and OECD Guideline 402 (Acute Dermal Toxicity) was carried out. Nicotinamide was tested for acute toxicity after single dermal application to rabbits. The test substance, available as a white, crystalline powder, was moistened with water and placed on the shorn dorsal skin of 5 male and 5 female animals under occlusive conditions for 24 hours. The dose was 2000 mg/kg bw (limit concentration). The only sign of toxicity was a slight reddening of the application site detected immediately after removal of the patches. The finding was present in some animals up to the end of the observation period. Deaths did not occur. At necropsy no abnormal findings, except the slight reddening at the application site, were recorded. The LD 50 values for male as well as female rabbits were above 2000 mg/kg bw (limit test). Nicotinamide was considered practically non-toxic.