Nicotinic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Nicotinic acid

EC Number:

200-441-0

EC Name:

Nicotinic acid

Cas Number:

59-67-6

Molecular formula:

C6H5NO2

IUPAC Name:

nicotinic acid

Test material form:

solid: crystalline

Details on test material:

- Name of test material: Nicotinic acid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Mean body weight: 104.1 +/- 1.9 g (males) and 95.8 +/- 1.1 g (females)
- Housed in groups of five in screen-bottomed stainless steel cages, in a well-ventilated room, maintained at 23 +/1 1 degree C
- Stock diet and tap water were provided.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

as 33% suspension in 0.5% aqueous solution of carboxymethyl cellulose

Details on oral exposure:

- Formulation: 33 % (w/v) aqueous solution, by oral gavage
- Volumes: 10.0 mL/kg to 20.7 mL/kg.

Doses:

3.30, 3.96, 4.75, 5.71 and 6.83 g/kg body weight.

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

The test substance was given by gavage as a 33 % (w/v) suspension in a 0.5 % aqueous solution of carboxy methyl cellulose (CMC) to groups of ten males and ten females in single doses of 10.0, 12.0, 14.4, 17.3 or 20.7 ml/kg body weight. After treatment, the rats received stock diet and tap water ad libitum. They were observed for signs of intoxication during a 14-day period, after which autopsies were carried out on the survivors.

Statistics:

The LD50 values were calculated according to the method of Weil (Biometrics 8 (1952): 249-263) for males and females separately, both after 24 hours and after 14 days.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

5 210 mg/kg bw

Based on:

test mat.

95% CL:

> 4 740 - < 5 730

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

4 500 mg/kg bw

Based on:

test mat.

95% CL:

> 4 170 - < 4 860

Mortality:

At 24 hours after dosing, 1 male and 2 females in the 2.88 g/kg group had expired, as did 4 each (male and female) in the 3.44 g/kg group, and 5 males and 7 females from the 4.16 g/kg dose group. After 14 days, no additional animals died in the 2.88 g/kg group. However, the total number of deaths at 14 days in the two higher groups were: 5 males and 4 females in the 3.44 g/kg group and 8 males and 8 females in the 4.16 g/kg group.

Clinical signs:

other: Within one hour after dosing, the rats showed sluggishness and signs of ataxia. Later on coma was frequently observed. Most of the deaths occurred between 1 and 20 hours after dosing. Three males and three females, however, succumbed between day 2 and 4

Gross pathology:

Macroscopic examination of the survivors at autopsy did not reveal any treatment—related gross alterations.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

An acute oral toxicity test, similar to OECD 401 guideline, was undertaken on nicotinic acid. Male and female Wistar rats were given solutions of the test substance suspended in CMC at concentrations ranging from 3.30-6.83 g/kg bw, and observed for 14 days. The LD50 was found to be 5.21 g/kg bw in males and 4.50 g/kg bw in females.

Executive summary:

A study similar or equivalent to OECD Guideline 401 (Acute toxicity oral) was carried out. Male and female Wistar rats were given solutions of the test substance suspended in CMC at concentrations ranging from 3.30-6.83 g/kg bw, and observed for 14 days. The LD50 was found to be 5210 mg/kg bw in males and 4500 mg/kg bw in females. The test item was considered to be practically non-toxic.