Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983-07-07 to 1983-07-27
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP compliance claim, no International Test Guidelines quoted (but all parameters are closely comparable to a guideline method) and the purity of the test substance is not reported.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A preliminary study was conducted using single oral doses of 1.0 and 5.0 g/kg in two male and two female rats at each dose level. The preliminary rats were observed for clinical signs and mortality over a period of five days.
On the basis of the results of the preliminary study, the main study was conducted at dose levels 0 (control), 1.6, 2.5, 4.0, and 5.0 g/kg bodyweight. Five rats of each sex were used at each dose level. Following a single oral dose, the rats were observed for clinical signs and mortality over a period of fourteen days. Bodyweights were recorded on days 1, 8, and 15. All surviving animals were sacrificed at day 15, and a macroscopic post mortem examination was conducted on all rats at death.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3-Methyl-3-methoxybutyl acetate
- Physical state: transparent, colourless liquid
- Storage condition of test material: Ambient temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hacking and Churchill Limited, Huntingdon, Cambridgeshire, England
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 90 - 131 g
- Fasting period before study: Overnight
- Housing: Metal cages with wire mesh floors
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Minimun period of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25-29
- Mean Relative Humidity (%): 57
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not applicable - test material was dosed as supplied.

MAXIMUM DOSE VOLUME APPLIED: 5.2 mL/Kg (specific gravity = 0.96 g/mL)
Doses:
0 (control=distilled water), 1.6, 2.5, 4.0, and 5.0 g/kg in main study
1.0 and 5.0 g/kg in preliminary study
No. of animals per sex per dose:
5/sex/group in the main study
2/sex/group in preliminary study
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days (5 days for preliminary study)
- Frequency of observations and weighing: observations were taken regularly on day 1, and at least twice daily on subsequent days. Bodyweights were recorded on days 1, 8, and 15, and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of:
Finney (1971) Probit Analysis (3rd Edition) Cambridge University Press.

Results and discussion

Preliminary study:
The results of the preliminary study indicated that the acute median lethal oral dose (LD50) to rats of 3-methyl-3-methoxybutyl acetate was between 1.0 and 5.0 g/kg bodyweight.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 600 mg/kg bw
Based on:
test mat.
95% CL:
4 200 - 5 000
Sex:
male
Dose descriptor:
LD50
Effect level:
4 700 mg/kg bw
Based on:
test mat.
95% CL:
4 100 - 5 400
Sex:
female
Dose descriptor:
LD50
Effect level:
4 500 mg/kg bw
Based on:
test mat.
95% CL:
3 900 - 5 100
Mortality:
Mortailties occurred amongst rats treated at 4.0 and 5.0 g/kg bodyweight within 22 to 71 hours of dosing.
3 males and 3 females dosed at 5.0 g/kg were found dead at the first observation of day 2; a further male from this group was found dead at the first observation on day 3 and a further female at the second observation of day 3. One female rat dosed at 4.0 g/kg was found dead at the first observation of day 4.
Clinical signs:
Abnormal body carriage (hunched posture), lethargy, decreased respiratory rate, increased salivation and ataxia was observed amongst treated rats.
Ptosis was seen in all rats treated at 2.5 g/kg and above.
Comatose-like condition was seen amongst rats treated at 4.0 and 5.0 g/kg.
Increased lacrimation was seen in four rats at 4.0 g/kg.
Pilo-erection only was observed in control animals.
Body weight:
Poor weight gain was recorded in the occasional male rat at 2.5 g/kg and above and the occasional treated female rat on Day 8. Bodyweight gains were normal on Day 15.
Gross pathology:
Terminal autospy findings were normal.

Any other information on results incl. tables

Dose (g/kg) Mortality ratio(No.ofdeaths)/(No.dosed) Time of death
after dosing
Males Females Combined
 1.0   0/2   0/2   0/4   - 
 5.0   2/2   2/2   4/4   <22 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute median lethal oral dose and their 95% confidence limits to rats of MMB-Ac were estimated to be:
Males and females combined: 4.6 (4.2 to 5.0) g/kg bodyweight
Males Only: 4.7 (4.1 to 5.4) g/kg bodyweight
Females Only: 4.5 (3.9 to 5.1) g/kg bodyweight