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Toxicological information

Acute Toxicity: oral

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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:
comparable to guideline study with acceptable restrictions

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)
Deviations:
yes
Remarks:
no males tested; but no differences betweeen males and females noted in preliminary tests
Principles of method if other than guideline:
Method: other: similar to OECD Guide-line 401
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Isobutylamine
EC Number:
201-145-4
EC Name:
Isobutylamine
Cas Number:
78-81-9
Molecular formula:
C4H11N
IUPAC Name:
2-methylpropan-1-amine
Details on test material:
Isobutylamine: no further details reported
- Name of test material (as cited in study report): isobutylamine
- Physical state: liquid
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG
- Age at study initiation: not stated
- Weight at study initiation: mean 172 g (S.D. +/- 3.31 g; range: 160-172 g; n=50)
- Fasting period before study: 16 hours
- Housing: in plastic cages on wood shavings
- Diet: standard diet ALTROMIN 1324 ad libitum
- Water: tap water, ad libitum
- Acclimation period: not stated


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not stated
- Humidity (%): not stated
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): not stated


IN-LIFE DATES:
From: treatment To: end of the14-day observation period

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 5%
- Amount of vehicle (if gavage): variable; 5 to 20 mL/kg
- Justification for choice of vehicle: solubility
- Purity: deionized water


MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

Doses:
250, 400, 630, 800, 1000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: rats were observed daily; body weights were recorded weekly
- Necropsy of survivors performed: yes
- Necropsy of animals that died: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
Probit analysis (according to Lindner and Weber) was used to determine the LD50 value. Company software was also used to calculate the confidence range according to Fieller.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
591 mg/kg bw
95% CL:
491 - 674
Mortality:
Deaths occurred within 3 hours and 10 days after dosing.
Clinical signs:
Symptoms included squatting position, unkempt fur, unsteady gait, abdominal position, apathy, closed lids, and forced breathing.
No symptoms were noted after 48 hours in animals that survived.
Body weight:
Body weights were clearly reduced in 3 and 4 animals at 400 and 630 mg/kg bw during the first week after dosing and normal thereafter.

Gross pathology:
Animals that died: necropsy revealed macroscopically changes of the gastrointestinal blood vessels and red-brownish mucus in the stomach and in the small intestine. The stomach contents showed a pH of 11.1 and were positively tested for blood.
Animals sacrificed: the terminal necropsy of sacrificed animals revealed a pattern of the liver lobules, blue coloring of the diaphragm and the peritoneum, and a dark brown color of the liver and spleen.

Any other information on results incl. tables

No differences were noted between male and female animals in preliminary experiments .

Dose

(mg/kg bw)

Mortalities

per group

250

0/10

400

1/10

630

4/10

800

10/10

1000

10/10

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Isobutylamine, oral LD50, rat, male and female: 591 mg/kg bw
Executive summary:

The oral LD50 of isobutylamine (rat, male and female) was 591 mg/kg bw in a valid non-GLP study (RL=2) that was conducted similar to OECD TG 401 using female rats. As no differences were noted between male and female animals in preliminary experiments, the LD50 is considered to be valid for both male and female rats. Gross pathology of animals that died revealed a high pH of 11.1 in the stomach, and congestion of the stomach blood vessels and teh GI tract (Hoechst, 1979).