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Description of key information

Isobutylamine was tested for acute oral toxicity in Wistar rats and Sprague-Dawley rats. Both non GLP studies were conducted with a method similar or comparable to the OECD 401 guideline.

In the first study (Hoechst 1979) the Oral LD50 in female Wistar rats was determined to be 591 mg/kg and in the second study publised (The acute Oral toxcity of isomeric Monobutylamines in the adult male and female rat; Toxicology and appied Pharmacology 63, 150 -152 (1982)), the Oral LD50 in male and female Sprague-Dawley rats was found to be 228 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
data were published in 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
no guideline followed
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Isobutylamine (>98%) was purchased from Tidom Chemical Inc., Hauppauge, New York
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Massachusetts.
- Age at study initiation: adult rats; all animals testes were from the same age.
- Fasting period before study: 18 hours
- Housing: two animals per cage
- Diet: Rodent Laboratory Chow (Ralston Purina Co., St. Louis, Mo.)
- Water: Tab water was available ad libitum
- Acclimation period: 2 weeks
- Weight: males 194.7 ± 20.5 g and females 156 ± 16.8 g

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 to 26°C
- Humidity (%): 22 to 49%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): A 12 hours light-dark schedule was maintained with the light cycle beginning at 7:00 AM

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100, 200, 300, 400, 500 and 600 mg/kg body wt
- Amount of vehicle (if gavage): constant 4 ml volume

MAXIMUM DOSE VOLUME APPLIED: 600 mg/kg body

CLASS METHOD
- Rationale for the selection of the starting dose: in a range-finding study, rats were treated in groups of two males and two females with various amoutns of the test compound.
Doses:
100, 200, 300, 400, 500 and 600 mg/kg body wt
No. of animals per sex per dose:
24 dosage groups, each group consisting of 10 male and 10 female rats
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not specified
- Necropsy of survivors performed: no
- Other examinations performed: signs of toxicity included sedation, ataxia, nasal discharge, gasping, salivation and , at higher doses, convulsions and death
- Gross pathological examination of animals that died following treatment
Statistics:
Data for male and females were compared statistically for each compound by the χ2 contigency table analysis (Snedecor and Cochran, 1967).
The LD50 value was calculated by the probit method of D.J. Finney (1971, Probit Analysis, 3rd ed., Cambridge Univ. Press, Cambridge)
Preliminary study:
In a range-finding study, rats were treated in groups of two males and two females with various amount of the test compount.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
224.4 mg/kg bw
95% CL:
>= 136.3 - <= 303.1
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
231.8 mg/kg bw
95% CL:
>= 106.1 - <= 345.9
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
227.9 mg/kg bw
95% CL:
>= 161.5 - <= 289.5
Mortality:
At the dose levels tested, death generally occurred within 1 to 3 hr after adminisation of the test substance.
Clinical signs:
sedation, ataxia, nasal discharge, gasping, salivation and, at higher doses convulstions and death
Body weight:
males 194.7 ± 20.5 g and females 156 ± 16.8 g at the initiation of the toxicity experiment
Gross pathology:
pulmonary edema
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The single-dose LD50 value was of 224.4 mg/kg body wt for the males and 231.8 mg/kg body wt for females rates; for males + females, it results in a LD50 value of 227.9 mg/kg body wt. The study is comparable to a study guideline with acceptable deviations. Therefore, it can be used for GHS classification.
Executive summary:

This paper reports the acute oral toxicity of the test substance in male and female rats. The test substance was administrated by gavage to all rats with the corresponding dosage groups. The solution of the test substance were preapred in corn oil such that doses of 100, 200, 300, 400, 500 and 600 mg/kg body weight.

The single-dose LD50 value was of 224.4 mg/kg body wt for the males and 231.8 mg/kg body wt for females rates; for males + females, it results in a LD50 value of 227.9 mg/kg body wt.

The study is comparable to a study guideline with acceptable deviations. Therefore, it can be used for GHS classification.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
228 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the above stated assessment of the acute oral toxicity, isobutylamine does have to be classified as Acute Toxicity Oral Category 3 (H301 Toxic if swallowed) according to CLP (Regulation (EC) No 1272/2008 Of the European parliament and of the Council.

Although the acute toxicity of the substance is related to corrosive properties, there is sufficient evidence that the substance maybe harmful by acute exposure and is therefore also classified as acute dermal toxicity Category 3 (H311 Toxic in contact with skin) and acute inhalation toxicity Category 3 (H331 Toxic if inhaled).

The substance may also cause respiratory irritation following inhalation exposure and is therefore also classified as STOT SE Category 3.