2-methylbutyric acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

other: TSCAT submission

Title:

Unnamed

Year:

1992

Report Date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): 2-methylbutyric acid
- Analytical purity: 97.9%
- Impurities (identity and concentrations): valeric acid 1.8%; unidentified 0.3%
- Stability under test conditions: shell life > 6 months
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 - 300 g
- Fasting period before study: overnight
- Diet: standard lab diet ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4 mL/kg bw

Doses:

males: 1.0, 2.0, 4.0 mL/kg bw
females: 0.25, 0.5, 1.0, 2.0, 4.0 mL/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 0 (prior to treatment), 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 value was calculated using the moving average method (Thompson, 1947; Weil, 1983)

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 750 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Using a density of 0.936 kg/L, the calculated LD50 of 1.87 mL/kg bw is equivalent to 1750 mg/kg bw

Mortality:

Most deaths occurred at 1.5 to 2 days. However, three females died at 10 to 14 days. Survivors recovered at one to three days.

Males: 0/5, 3/5 and 5/5 of the low, middle and high dose group died
Females: 0/5, 0/5, 1/5, 2/5, 5/5 of the 0.25, 0.5, 1, 2, 4 mL/kg bw dose group died, respectively

Clinical signs:

Signs of toxicity included sluggishness, lacrimation, unkempt fur, kyphosis (in 2), prostration, a moribund appearance, diarrhea, red to brown discharge on perioral, perinasal and periurogenital fur.

Body weight:

Males: body weight gain at 1.0 mL/kg bw; bodyw eight reduced at 2.0 mL/kg bw
Females: no body weight gain at all dose levels

Gross pathology:

Dead animals: stomach abnormalities (discoloration, brown liquid or gas, gastric collapse); discoloure dlungs; brown to dark red livers, intstines, and kidneys.
Survivors: small stomachs and spleens; rough stomach surfaces, adhesion of the stomach to liver or spleen, enlarged and mottled red kidneys.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 was 1750 mg/kg bw in male and female rats. Necropsy findings in survivors revealed irritation/corrosion of the stomach and intestines.

Executive summary:

Oral toxicity was investigated in a study similar to OECD TG 401. Male and female rats (n=5 per sex per dose) were exposed against different doses of test substance up to 4 mL/kg bw (3744 mg/kg bw by calculation on basis of substance density of 0.936 kg/L). Exposed animals showed signs of toxicity including sluggishness, lacrimation, unkempt fur, kyphosis, prostration, a moribund appearance, diarrhea, red to brown discharge on perioral, perinasal and periurogenital fur. Female rats of all dose groups and male rats at doses >= 2 mL/kg bw did not gain body weight. The following findings were observed at necropsy of dead animals: stomach abnormalities (discoloration, brown liquid or gas, gastric collapse), discoloured lungs, brown to dark red livers, intstines, and kidneys. Necropsy of the surving animals revealed the following effects: small stomachs and spleens; rough stomach surfaces, adhesion of the stomach to liver or spleen, enlarged and mottled red kidneys.Using the moving average method an LD50 value of 1.87 mL/kg bw (corresponding to 1750 mg/kg bw) was calculated for male and female rats.