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Description of key information

Acute oral toxicity:


LD50 >5000mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
3 Mar 1988 to 17 March 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
25 April 1984
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
24 February 1987
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: KFM-Han. Wistar-[rat]
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf / Switzerland
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: Males: 210 - 225 g, Females: 171 - 200 g
- Fasting period before study: 12 - 18 hours
- Housing: Groups of 5 in Makrolon type-3 cages with standard softwood bedding
- Diet: ad libitum, Pelleted standard Kliba 343, rat naintenance diet, Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland
- Water: ad libitum, tap water
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality/viability: 4 times during test day 1 and daily during days 2-15. Body weights: on test days 1 (pre-administration), 8 and 15. Clinical signs and symptoms were examined 4 times during day 1 and daily during days 2-15.
- Necropsy of survivors performed: yes
Statistics:
The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
other: Symptoms of sedation, hunched posture and ruffled fur was observed in all test animals within the first 24 hours following application. No clinical signs were noted at later observation time points.
Gross pathology:
No macroscopic organ changes were observed.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 5 000 mg/kg bw

Additional information




Acute oral toxicity:


In an acute oral toxicity study in Wistar rats according to OECD Guideline 401 and GLP, the test substance was administered via gavage in polyethylene glycol at 5000 mg/kg bw to 5 males and 5 females. No mortality was found over the course of 15 days, the expected body weight gain was observed. Clinical signs included sedation, hunched posture and ruffled fur in the first 24 hours following application. No macroscopic changes were reported following necropsy at the end of the study period. Therefore, the LD50 in rats was determined as >5000 mg/kg bw.


These findings are supported by a non-GLP OECD guideline 401 study in Wistar rats (no RSS included in IULCID, but can be provided if requested), in which the test substance was administered at 1000 or 5000 mg/kg bw in 2% CMC as gavage to 5 males and 5 females per dose group. No mortality was observed in the course of 14 days and the expected body weight gain was recorded. Clinical signs observed were ruffled fur at 1000 mg/kg bw and ruffled fur as well as dyspnea at 5000 mg/kg bw. All clinical signs were resolved within 3 days following substance application. Gross pathology reported mottled lungs in 3/5 males in the 1000 mg/kg bw group, the other rats showed no macroscopic organ changes. Therefore, the LD50 in rats was determined as >5000 mg/kg bw under the conditions tested.


In an acute oral toxicity study in NMRI mice according to OECD guideline 401 and GLP, the test substance was administered via gavage in polyethylene glycol at doses of 1000 or 5000 mg/kg bw to 5 males and 5 females per dose. No mortality was observed over the course of 14 days, the expected body weight gain was recorded. No clinical signs were observed at 1000 mg/kg bw, in the 5000 mg/kg bw group dyspnea and ruffled fur were observed within the first 4 days following application. No gross organ changes were recorded at necropsy at the end of the study period. Therefore, the LD50 in mice was determined at >5000 mg/kg bw.




Justification for classification or non-classification

Based on the data available and laying down the criteria specified in Regulation (EC) 1272/2008, no classification for acute toxicity is warranted.