Isovaleric 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:

other: Basic data given: comparable to guideline studies

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

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:

Isovaleric acid

EC Number:

207-975-3

EC Name:

Isovaleric acid

Cas Number:

503-74-2

Molecular formula:

C5H10O2

IUPAC Name:

3-methylbutanoic acid

Details on test material:

- Name of test material (as cited in study report): Isovaleriansäure; substance No. 77/520

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: males 184 g ; females 162 g (means)
- Fasting period before study: 15-20 hr

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5% and 1-2 drops of Chremophore El.

Details on oral exposure:

VEHICLE
- Concentration in vehicle:6.8 - 50%
- Amount of vehicle (if gavage): dose volume: 10 mL/kg bw
- Justification for choice of vehicle: aqueous solution of 0.5% CMC

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

681, 1000, 1470, 2150, 2610, 3160, 3830, and 5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not needed

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: daily; weighing: on days 0, 2-4, 7, and 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 500 mg/kg bw

Based on:

test mat.

Mortality:

see table below

Clinical signs:

other: Dyspnea, apathy, unkempt fur, and poor condition was seen at 1000 mg/kg bw and above. Cyanosis, atony, unsteady gait was seen at 1470 mg/kg bw and above; narcosis, impaired pain reflexes, trembling, exsiccation and exophthalmia was seen at 2610 mg/kg bw a

Gross pathology:

Dead animals: heart: hyperaemic congesting; glandular stomach: haemorrhage, gastritis; intestine: reddened mucosa, injected vessels.
Surviving animals: forestomach: button formation (in groups 1470-3160 mg/kg bw; wall thickened in animals at 215ß-3160 mg/kg bw. No changes in animals at 681-1000 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of isovaleric acid was approx. 2500 mg/kg bw in male and female rats

Executive summary:

The acute oral toxicity of isovaleric acid was determined in male and female Sprague-Dawley similar to OECD 401 (5 rats/sex; oral gavage; test substance at 681, 1000, 1470, 2150, 2610, 3160, 3830, and 5000 mg/kg bw in 0.5% CMC; observation period 14 days). Signs of toxicity were seen at 1000 mg/kg bw and above in a dose-dependent manner. No deaths occurred at doses up to and including 2150 mg/kg bw, with a steep increase of mortality at higher doses. The LD₅₀was ca. 2500 mg/kg bw for male and female rats. Necropsy revealed lesions in the stomach and intestine that are attributable to the irritating property of the isovaleric acid (BASF, 1980).

The study is considered to be valid and suitable for assessment.