Registration Dossier

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: Non-GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1976

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
not specified
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Methylbutinol

Test animals

Species:
rat
Strain:
other: Albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: Young
- Weight at study initiation: 200-300 grams
- Fasting period before study: 24 hours
- Housing: common cage
- 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: 4000 mg/kg bw
Doses:
Male/female: 500, 1000, 1250, 1600, 2000, 3200 and 4000 mg/kg bw
No. of animals per sex per dose:
5 male, 5 female per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD0
Effect level:
1 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 410 mg/kg bw
Based on:
test mat.
95% CL:
1.06 - 1.88
Sex:
male
Dose descriptor:
LD100
Effect level:
2 500 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD0
Effect level:
500 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
1 620 mg/kg bw
Based on:
test mat.
95% CL:
1.32 - 2
Sex:
female
Dose descriptor:
LD100
Effect level:
2 500 mg/kg bw
Based on:
test mat.
Mortality:
Males
Group Dose level (mg/kg bw) Survivors Deaths
I 500 5 0
II 1000 5 0
III 1250 3 2
IV 1600 2 3
V 2000 1 4
VI 2500 0 5
VII 3200 0 5
VIII 4000 0 5

Females
Group Dose level (mg/kg bw) Survivors Deaths
I 0.5 5 0
II 1 4 1
III 1 4 1
IV 1.6 3 2
V 2 1 4
VI 2.5 0 5
VII 3.2 0 5
VIII 4 0 5
Clinical signs:
Males:
The animals dosed at 500 mg/kg bw and 1000 mg/kg bw were sluggish with unkempt coats for 36 - 48 hours. Staggering gait, impaired locomotion, labored breathing, and lethargy were noted after intubation at levels ranging from 1250 mg/kg bw to 2500 mg/kg bw. On the second day of observation, complete loss of motor control and ocular hemorrhage commenced. Survivors remained debilitated throughout the observation period.
Complete loss of motor control, labored breathing and lethargy were noted prior to comas and death at 3200 mg/kg bw and 4000 mg/kg bw.

Females:
The animals dosed at 500 mg/kg bw and 1000 mg/kg bw were sluggish with unkempt coats for 36 - 48 hours. Staggering gait, impaired locomotion, labored breathing, and lethargy were noted after intubation at levels ranging from 1250 mg/kg bw to 2500 mg/kg bw. On the second day of observation, complete loss of motor control and ocular hemorrhage commenced. Survivors remained debilitated throughout the observation period.
Complete los s of motor control, labored breathing and lethargy were noted prior to comas and death at 3200 mg/kg bw and 4000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute toxicity study revealed LD50 values of 1410 mg/kg bw for males and 1620 mg/kg bw for females.
Executive summary:

An acute oral toxicity study was carried out according to a method similar or equivalent to EU method B.1 and OECD guideline 401. Male and female rats were administered doses of 500, 1000, 1250, 1600, 2000, 3200 and 4000 mg/kg bw per oral gavage. The resulting LD50 value for males was 1410 mg/kg bw and the LD50 value for females was 1620 mg/kg bw.