Nicotinamide

Acute Toxicity: dermal

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Nicotinamide

EC Number:

202-713-4

EC Name:

Nicotinamide

Cas Number:

98-92-0

Molecular formula:

C6H6N2O

IUPAC Name:

nicotinamide

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 or test system 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 levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: 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.

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.