Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study methodology followed was equivalent or similar to EU Method B.1 and in accordance with the Principles of GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
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): Methyl proxitol
- Physical state: clear, colourless liquid
- Analytical purity: not specified in the report
- Impurities (identity and concentrations): not specified in the report
- Composition of test material, percentage of components: sec. methyl mono proxitol - 97.7%, prim. methyl mono proxitol - 2.06%, unknowns - 0.01%, propylene oxide - < 0.01%, methanol - 0.12%, water - 0.09%, acidity (as acetic acid) - 0.001%
- Isomers composition: not specified in the report
- Purity test date: not specified in the report
- Lot/batch No.: Indent 9200/9075
- Expiration date of the lot/batch:
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions: stable as per infra-red spectra
- Storage condition of test material: stored in the dark at ambient temperature

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 180-250 g (male) and 110-170 g (female)
- Fasting period before study: overnight fasting (18 hours)
- Housing: 2-3 rats/cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not specified in the report

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): not specified in the report
- Air changes (per hr): not specified in the report
- Photoperiod (hrs dark / hrs light): 12 hours light:dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test material was administered undiluted.
Doses:
2500, 3150, 3970 and 5000 mg/kg
No. of animals per sex per dose:
5 males + 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: initial, day 7 and day 14
- Necropsy of survivors performed: yes
Statistics:
probit analysis

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
4 277 mg/kg bw
95% CL:
3 478 - 5 572
Sex:
male
Dose descriptor:
LD50
Effect level:
3 739 mg/kg bw
95% CL:
2 573 - 7 986
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 016 mg/kg bw
95% CL:
3 503 - 4 915
Mortality:
Refer to Table 1 for further details.
Clinical signs:
Refer to Tables 2 and 3 for further details, rats in all the dose groups were overtly affected, the commonest clinical signs being gait abnormalities, chromodacryorrhoea and piloerection. The majority of the rats that died were comatose prior to death - in some cases they were unconscious for 48 hours or more before death. Four rats from the 3970 mg/kg dose group and one male from the 5000 mg/kg dose group were comatose for part or all of day 2 but recovered
Body weight:
All surviving animals had gained weight relative to their day 0 body weights by the end of the 14-day observation period
Gross pathology:
Refer to Tables 2 and 3 for further details
Other findings:
- Organ weights: no data
- Histopathology: no data
- Potential target organs: no data

Any other information on results incl. tables

Table 1: Mortality Table

Dose (mg/kg)        Cummulative mortality (14 days)
   Male  Female  Total
 2500 1/5  0/5  1/10 
 3150 1/5  0/5  1/10 
 3970 3/5  2/5  5/10 
 5000 4/5  4/5  8/10 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, the LD50 for methyl proxitol to rats (combined) was 4016 mg/kg (3503-4915 mg/kg), for females was 4277 mg/kg (3478-5572 mg/kg) and for males was 3739 mg/kg (2573-7986 mg/kg)
Executive summary:

The acute oral toxicity of methyl proxitol was evaluated in groups of rats (5 males + 5 females) at doses of 2500, 3150, 3970 and 5000 mg/kg. Mortality was observed in all the dose groups. Rats in all the dose groups were overtly affected, the commonest clinical signs being gait abnormalities, chromodacryorrhoea and piloerection. The majority of the rats that died were comatose prior to death - in some cases they were unconscious for 48 hours or more before death. Four rats from the 3970 mg/kg dose group and one male from the 5000 mg/kg dose group were comatose for part or all of day 2 but recovered. All surviving animals had gained weight relative to their day 0 body weights by the end of the 14-day observation period. Based on the results of the study, the LD50 for methyl proxitol to rats (combined) was 4016 mg/kg (3503-4915 mg/kg), for females was 4277 mg/kg (3478-5572 mg/kg) and for males was 3739 mg/kg (2573-7986 mg/kg)