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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 Jan 1991 - 27 Feb 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1981)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health and Social Security of the Government of the United Kingdom
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Chales River (UK) Ltd., Manston, Kent, U. K.- Age at study initiation: approximately 5-8 weeks- Weight at study initiation: 26-30 g (males), 20-24 g (females)- Fasting period before study: 2-4 hours prior to gavage and 2 hours after gavage- Housing: in groups of 5 by sex in solid-floor polypropylene cages with sawdust bedding- Diet (ad libitum): Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U. K.- Water (ad libitum)- Acclimation period: at least 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 17-24- Humidity (%): 34-84- Air changes (per hr): 15- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 0.83 ml/kg bw for the high dose groupDOSAGE PREPARATION: The volumes for each dose group were determined according to the specific gravity of the test material and the animals' fasted body weight at the time of dosing.
Doses:
500, 707, and 1000 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: 0.5, 1, 2, and 4 hours post-dosing, and subsequently once daily until study termination- Frequency of weighing: on days 0, 7 and 14, or at death- Necropsy of survivors performed: yes- Other examinations performed: careful examination of gastro-intestinal tract for signs of corrosion

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
472 mg/kg bw
Based on:
test mat.
95% CL:
234 - 953
Remarks on result:
other: Deaths are supposed to be contributed to irritation or corrosion of gastro-intestinal tract rather than systemic toxicity.
Sex:
male
Dose descriptor:
LD50
Effect level:
149 mg/kg bw
Based on:
test mat.
95% CL:
5 - 4 757
Sex:
female
Dose descriptor:
LD50
Effect level:
841 mg/kg bw
Based on:
test mat.
95% CL:
707 - 1 000
Mortality:
All animals treated at a dose level of 1000 mg/kg bw died the day of dosing or one or two days after dosing. One male and one female were killed in extremis on day 3. All males treated at a dose level of 707 mg/kg bw died. The deaths occured between one and four days after dosing. Four males died at a dose level of 500 mg/kg bw. Two of these animals died within 30 min of dosing and the other two animals died one or three days after dosing. Three females treated at a dose level of 500 mg/kg bw died one day after dosing.
Clinical signs:
Common signs of toxicity noted in all dose groups were hunched posture, lethargy, ptosis, laboured respiration, ataxia, and piloerection. Additional signs of loss of righting reflex were noted in animals treated with 707 and 1000 mg/kg bw. Isolated signs of toxicity noted were distended abdomen in animals treated with 500 mg/kg bw and decreased respiratory rate, dehydration, pallor of the extremities, and hypothermia in animals treated with 1000 mg/kg bw. All surviving animals appeared normal nine days after treatment and for the remainder of the study period.
Body weight:
Surviving animals showed little or no gain in body weight during the study except for one male treated with 500 mg/kg bw and one female treated with 707 mg/kg bw. These animals showed a loss in body weight during the first week of the study.
Gross pathology:
Abnormalities generally seen at necropsy of animals that died during the study were haemorrhagic or abnormally red lungs, dark liver or patchy pallor of the liver and dark kidneys. Commonly noted effects on the gastro-intestinal tract were haemorrhage of the small intestines and gastric mucosa. Haemorrhage of the large intestine was noted in one male treated with 500 mg/kg bw and one male and two females treated with 1000 mg/kg bw; sloughing of the non-glandular epithelium was noted in three males treated with 500 mg/kg bw and one male and two females treated with 1000 mg/kg bw. No abnormalities were in one male and two females treated with 500 mg/kg bw and all females treated with 707 mg/kg bw that were killed at the ned of the study. A necropsy was not performed on one male that died after a dose of 707 mg/kg bw. This omission was due to an oversight but was considered not to affect the purpose or integrity of the study.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS Category 4 (H302) according to Regulation (EC) No 1272/2008