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Description of key information

The oral LD50 of the test substance was determined to be 690 mg/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:
1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: CM 193 from 29.12.1987
- Purity test date: 20.01.1988

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the dark at 22°C under ventilation hood
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, Kastengrund, SPF-Zucht
- Age at study initiation: females: ca 7 weeks; males: ca. 9 weeks
- Weight at study initiation: females: 171-184 g; males: 171-196 g
- Fasting period before study: 16 h before and 3-4 h after dose adminstration
- Housing: Type 4 macrolon cage on wooden chips in groups of 5 animals/cage
- Diet (e.g. ad libitum): Altromin 1324, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
- Application volume: 10 ml/kg bw
Doses:
- Males: 500 mg/kg bw
- Females: 600, 670, 710 and 800 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs: daily; bodyweight: weekly
- Necropsy of survivors performed: yes
Statistics:
The LD50 values were calculated by PROBIT analysis.
Key result
Dose descriptor:
LD50
Effect level:
690 mg/kg bw
Mortality:
- Males: 500 mg/kg bw: 0/5
- Females: 600 mg/kg bw: 0/5; 670 mg/kg bw: 2/5; 710 mg/kg bw: 3/5; 800 mg/kg bw: 5/5
Deaths occurred up to Day 5 following administration.
Clinical signs:
In both sexes: hunched posture, drawn flanks, decreased spontaneous activity, irregular breathing, stomach or flank position, crawling forward in crouching position, reduced or absent righting and paw pinch reflexes.
In some animals: rough fur and noisy breathing.
Female animals also showed high leg / irregular gait, diarrhea, wide stance, spasmodic breathing, red crusty nose, half- to entirely closed eyelids and clear tearing.
All clinical signs were reversible within 8 days after administration.
Body weight:
There was no effect on bodyweights.
Gross pathology:
In females that died in the course of the study: small spleen, dark spots in the lungs, gastrintestinal tract filled with test substance, small intestine filled with red-brown mass (confirmed to contain blood), small intestine filled with light yellow mass, bladder filled with dark liquid (confirmed to contain blood).
Animals sacrificed at test end showed no macroscopic signs.
Conclusions:
Under the study conditions, the LD50 (rat) of the test substance was determined to be 690 mg/kg bw.
Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance (94% purity) according to OECD Guideline 401, in compliance with GLP. Groups of 5 male and 5 female Wistar rats received doses of 500 mg/kg bw (males) or 600, 670, 710 and 800 mg/kg bw (females) diluted in sesame oil by oral gavage at 10 ml/kg bw. Mortality and clinical signs were assessed daily for 14 days. Bodyweights were recorded weekly. Gross macroscopy was conducted on animals dying during the study or sacrificed at the end of the study. There was no mortality in males and 0/5, 2/5, 3/5 and 5/5 deaths in females at 600, 670, 710 and 800 mg/kg bw, respectively. Clinical signs in both sexes included hunched posture, drawn flanks, decreased spontaneous activity, irregular breathing, stomach or flank position, crawling forward in crouching position, reduced or absent righting and paw pinch reflexes. Some animals showed rough fur and noisy breathing. Female animals also demonstrated high leg / irregular gait, diarrhea, wide stance, spasmodic breathing, red crusty nose, half- to entirely closed eyelids and clear tearing. All clinical signs were reversible within 8 days after administration. There was no effect on bodyweights. In females that died in the course of the study, small spleen, dark spots in the lungs, gastrintestinal tract filled with test substance, small intestine filled with red-brown mass (confirmed to contain blood), small intestine filled with light yellow mass, bladder filled with dark liquid (confirmed to contain blood) were seen. Animals sacrificed at test end showed no macroscopic signs. Under the study conditions, the LD50 of the test substance in rat was determined to be 690 mg/kg bw (Hofmann and Jung, 1988).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
690 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A study was conducted to determine the acute oral toxicity of the test substance (94% purity) according to OECD Guideline 401, in compliance with GLP. Groups of 5 male and 5 female Wistar rats received doses of 500 mg/kg bw (males) or 600, 670, 710 and 800 mg/kg bw (females) diluted in sesame oil by oral gavage at 10 ml/kg bw. Mortality and clinical signs were assessed daily for 14 days. Bodyweights were recorded weekly. Gross macroscopy was conducted on animals dying during the study or sacrificed at the end of the study. There was no mortality in males and 0/5, 2/5, 3/5 and 5/5 deaths in females at 600, 670, 710 and 800 mg/kg bw, respectively. Clinical signs in both sexes included hunched posture, drawn flanks, decreased spontaneous activity, irregular breathing, stomach or flank position, crawling forward in crouching position, reduced or absent righting and paw pinch reflexes. Some animals showed rough fur and noisy breathing. Female animals also demonstrated high leg / irregular gait, diarrhea, wide stance, spasmodic breathing, red crusty nose, half- to entirely closed eyelids and clear tearing. All clinical signs were reversible within 8 days after administration. There was no effect on bodyweights. In females that died in the course of the study, small spleen, dark spots in the lungs, gastrintestinal tract filled with test substance, small intestine filled with red-brown mass (confirmed to contain blood), small intestine filled with light yellow mass, bladder filled with dark liquid (confirmed to contain blood) were seen. Animals sacrificed at test end showed no macroscopic signs. Under the study conditions, the LD50 of the test substance in rat was determined to be 690 mg/kg bw (Hofmann and Jung, 1988).

Justification for classification or non-classification

Based on the LD50 value from the acute oral toxicity study, the test substance is considered to be moderately toxic via oral route and is classified as Category 4, H302: harmful if swallowed according to CLP criteria (EC 1272/2008).