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:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(only limited information on test procedure and test material identity are given, and no test material purity is stated in the study report)
Principles of method if other than guideline:
Only limited information on procedure and results is given in the study report. The test material was administered by stomach intubation to Wistar-derived male rats.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 3-4 weeks
- Weight at study initiation: 90-120 g
- Fasting period before study: none
- Diet: appropriate diet ad libitum (not further specified)
- Water: ad libitum (not further specified)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 16 mL/kg
Doses:
0.5, 1, 2, 4, 8, and 16 mL/kg bw, equivalent to 475, 950, 1900, 3800, 7600, and 15200 mg/kg bw (calculated based on a density of 0.95 g/cm³)
No. of animals per sex per dose:
5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The LD50 along with the 95% confidence limits was calculated by the moving average method based on a 14 day observation period.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
12 825 mg/kg bw
Based on:
test mat.
95% CL:
>= 551 - <= 3 192
Remarks on result:
other: (equivalent to 13.5 mL/kg bw (95% CL 5.38 - 33.6 mL/kg bw); calculated based on a density of 0.95 g/cm³)
Sex:
male
Dose descriptor:
LD0
Effect level:
475 mg/kg bw
Based on:
test mat.
Remarks on result:
other: (equivalent to 0.5 mL/kg bw; calculated based on a density of 0.95 g/cm³)
Mortality:
- 16 mL/kg bw: 3/5 (all animals died 30-35 min after dosing)
- 8 mLl/kg bw: 1/5 (animal died on day 7 post-dosing)
- 4 mL/kg bw: 2/5 (animals died 20 min after dosing and on day 1); repeated for confirmatory purpose: deaths 2/5 on days 0 and 1
- 2 mL/kg bw: 2/5 (deaths occured 15 and 20 min after dosing)
- 1 ml/kg bw: 1/5 (animal died 30 min after dosing)
- 0.5 mL/kg bw: 0/5
Clinical signs:
- 16 mL/kg bw: Sluggish (survivers) at 35 min; salivation
- 8 mL/kg bw: Diarrhoea at day 1
- 4 mL/kg bw: Salivation; repeated for confirmatory purpose: Unsteady gait; salivation 5 min after dosing; survivors recovered after 1 day.
- 2 mL/kg bw: Unsteady gait; salivation at 8 min
- 1 mL/kg bw: Salivation (the animal that died)
- 0.5 ml/kg bw: no clinical signs were observed during the study period.
Body weight:
Mean body weight changes seen throughout the study period were:
- 16 mL/kg bw: 64 g (21 and 107 g)
- 8 mL/kg bw: 107 g (94 to 123 g)
- 4 mL/kg bw: 112 g (100 to 126 g); repeated for confirmatory purpose: 125 g (121 to 134 g)
- 2 mL/kg bw: 120 g ( 112 to 125 g)
- 1 mL/kg bw: 123 g (119 to 132 g)
- 0.5 mL/kg bw: 102 g (71 to 125 g)
No further details are given in the study report.
Gross pathology:
In victims, the stomach was gas-filled, the glandular portions were injected, and the intestines were injected or contained blood.
In survivors, nothing remarkable was observed.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was tested for acute oral toxicity according to a test protocol that is comparable to the appropriate OECD test guideline, but without GLP compliance. The test material was administered by stomach intubation to 5 male rats each dose group. The LD50 was determined to be 12825 mg/kg bw. The predominant clinical signs detected were salivation, unsteady gait, sluggishness, and diarrhoea. No deaths and no clinical signs throughout the study period were observed at 425 mg/kg bw. Based on this data, classification for acute oral toxicity according to EC/1272/2008 is not warranted.