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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A well reported study conducted according to GLP and following a relevant guideline

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
- Name of test material (as cited in study report): 2-Aminobutanol
- Molecular formula (if other than submission substance): C4H11NO
- Physical state: Liquid
- Analytical purity: >98%
- Isomers composition: mix of D and L optical isomers. quantities unspecified.
- Stability under test conditions: 'indefinite'
- Solubility: miscible with water
- pH: 11.1 (0.1M aqueous solution)

Test animals

Details on test animals or test system and environmental conditions:
Purchased from Charles River Breeding Laboratories (Wilmington, MA). Animals were approximately 8-12 weeks of age at study start, weighing between 200 and 300 grams. 15 male and 15 female rats were used. All females were nulliparous and non-pregnant. Animals housed in individual polycarbonate cages, bedding provided (Hardwood Sani-chips). Animals maintained at 68+/-3 degrees F, relative humidity of 30-70%, 10 to 13 complete air changes per hour and a 12 h light/dark cycle. Food and water provided ad libitum.

Administration / exposure

Route of administration:
oral: gavage
unchanged (no vehicle)
Details on oral exposure:
A single dose of test material via intragastric intubation. No vehicle required.
0.8, 1.8 and 2.8 g/kg bw
No. of animals per sex per dose:
5 males and 5 females per dose group
Control animals:
Details on study design:
Animals dosed, then returned to cages and provided with feed and water ad libitum. Clinical observations conducte daily for 14 days. Any animal found dead prior to study termination was necropsied as soon as possible, in no case later than 12 hours after death. Gross necropsy performed on all animals found dead or sacrificed at end of study. Body weights determined on fasted animals at day 0, on day 7 and day 14.
Sacrifice of animals performed using carbon dioxide exposure.
If possible the Litchfield & Wilcoxon Pharmacological calculating system used to calculate LD50.

Results and discussion

Effect levelsopen allclose all
Dose descriptor:
Effect level:
ca. 2 800 mg/kg bw
Dose descriptor:
Effect level:
ca. 1 800 mg/kg bw
Dose descriptor:
Effect level:
ca. 800 mg/kg bw
Dose group 2.8 g/kg bw
9/10 animals died by day 1, remaining animal died on day 2.

Dose Group 1.8 g/kg bw
6 animals died (5 females and 1 male) by day 5 of the study, the remaining 4 males survived until study termination

Dose group 0.8 g/kg bw
No mortalities observed
Clinical signs:
other: Dose group 2.8 g/kg bw Abdominal breathing and lethargy noted at 4 hr observation period. Dose Group 1.8 g/kg bw Lethargy and prostration observed throughout the study Dose group 0.8 g/kg bw No clinical signs observed
Gross pathology:
Dose group 2.8 g/kg bw
No unusual lesions noted in any of the animals at Gross necropsy

Dose Group 1.8 g/kg bw
No unusual lesions noted in any of the animals at Gross necropsy

Dose Group 0.8 g/kg bw
No unusual lesions noted in any of the animals at Gross necropsy

Applicant's summary and conclusion

Interpretation of results:
Migrated information Criteria used for interpretation of results: EU
2-Aminobutanol (D/L) caused 10/10 mortalities at a dose of 2.8 g/kg bw in rats, 6/10 at a dose of 1.8 g/kg bw and 0/10 at a dose of 0.8 g/kg. It was not possible to use the Litchfield and Wilcoxon calculating system to statistically determine the LD50, therefore the LD50 was considered to be approximately 1.8 g/kg bw in rats.

Based on the difference in mortality between the sexes at the 1.8 g/kg bw dose it also appears that female rats may be more sensitive than males to the acute toxicity of 2-Aminobutanol. If the response of each sex is considered separately, the LD50 for males would be greater than 1.8 g/kg bw (approximately 2 g/kg bw), whereas the LD50 females would be between 0.8 and 1.8 g/kg bw. However no attempt was made in the original report to calculate LD50 values for each sex. Regardless of whether an individual sex LD50 is determined, the classification for acute toxicity remains the same.
Executive summary:

30 Sprague Dawley rats were used to determine the acute toxicity potential of 2-Aminobutanol (D/L). The test substance was dosed via gavage on day 0 of the study at doses of either 2.8, 1.8 or 0.8 g/kg bw (these doses were based on a range finding study conducted earlier, reference K-004657 -008). There were 5 males and 5 females per dose group and since there was no vehicle required, a control group was not incorporated into the study. At the top dose of 2.8 g/kg bw all 10 animals died within the first 2 days of the observation period. There were no gross legions noted at necropsy and clinical signs at the 4 hr time point were limited to abdominal breathing and lethargy. At the mid dose of 1.8 g/kg bw, 6 (1 male and 5 female) animals died, the 4 surviving males gained weight throughout the study until sacrifice. Clinical signs noted were limited to prostration and lethargy. No unusual legions were noted at necropsy. In the low dose group of 0.8 g/kg bw there were no mortalities, no clinical signs and no unusual legions seen at necropsy. The LD50 was estimated to be approximately 1.8 g/kg based on the 6/10 deaths at this dose group.