Nicotinamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

SafePharm Laboratories Ltd.

Test type:

acute toxic class 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:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: males weighed 211 to 240g, females 223 to 236g
- Fasting period before study: Overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: Housed in groups of three by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): Approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES
- From: 04 April 2000 To: 04 April 2000

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED
- 10 mL/kg bw

All animals were dosed once only by gavage. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each sex to confirm the survival of the previously dosed animals.

Doses:

2000 mg/kg bw (male/female)

No. of animals per sex per dose:

3 animals per sex and dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Frequency of observations and weighing: Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
- Necropsy of survivors performed: Yes
- Other examinations performed: All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded.

Statistics:

Not applicable.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 500 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:

There were no deaths.

Clinical signs:

other: Hunched posture was noted in all animals during the day of dosing and one day after dosing. Lethargy was also noted in two females during this time.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was estimated to be greater than 2500 mg/kg bw. The test item was considered practically non-toxic.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material following a single oral administration to the Sprague-Dawley CD strain rat. The method followed EU Method B.1 tris and OECD Guideline 423 (Acute Oral Toxicity - Acute Toxic Class Method). Using all available information, 2000 mg/kg bw was selected as the starting dose. A group of three fasted males was treated with the starting dose. This was followed by a group of three fasted animals of the other sex at the same dose level. The test material was administered orally as a solution in distilled water. The animals were observed1, 2 and 4 hours after dosing and then once daily for fourteen days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14. At the end of the observation period all animals were killed by cervical dislocation and subjected to gross necropsy. There were no deaths. Hunched posture was noted in all animals during the day of dosing and one day after dosing. Lethargy was also noted in two females during this time. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test material, in the Sprague-Dawley CD strain rat, was estimated as being greater than 2500 mg/kg bw. The test item was considered practically non-toxic.