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Toxicological information

Acute Toxicity: oral

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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 guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
SafePharm Laboratories Ltd.
Test type:
acute toxic class 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:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 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:
There were no deaths.
Clinical signs:
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.
Body weight:
All animals showed an expected gain in bodyweight during the study.
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.