Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1, 1982 to July 26, 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Study was conducted to GLP and was equivalent or similar to OECD 402.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
impurity
Specific details on test material used for the study:
The test material is a UVCB

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Fifty (25 males and 25 females) were selected based upon body weights. Rats were housed individually in stainless steel wire mesh cages in accordance with the 'Guide for the Care and use of Laboratory Animals' of the Institute of Laboratory Resources, National Research Council. Waste material was removed daily. Cages and feeders were sanitized every two weeks. food was provided ad libitum, checked daily and added or replaced as needed Fresh tap water was aslo available ad libitum for the duration of the study.

ENVIRONMENTAL CONDITIONS:

Temperature: 22◦C ± 3◦C
Humidity: 30 to 70%
Light cycle: 12 hours light, 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
Rats were exposed to the test material via oral gavage at a dose volume of 5ml/kg. The vehicle was 0.25% methylcellulose
Doses:
1000, 1600, 2500, 3200 and 4000 mg/kg
No. of animals per sex per dose:
10 (5 Males and 5 females) per dose group
Control animals:
no
Details on study design:
Five groups of 10 rats (5 females, 5 males) were fasted for 18 hours and aministered the test substance at doses of 1000, 1600, 2500, 3200 and 4000 mg/kg by oral gavage. The rats were observed immediatley after dosing and at one, four, and twenty four hours and once daily for fourteen dats for pharmacotoxic, CNS effects and mortality. On the fourteenth day body weights were recorded. The surviving rats were sacrificed by carbon dioxide inhalation and a gross necropsy performed.

Results and discussion

Preliminary study:
In a dose ranging study, four fasted animals, two per sex, were administered the test article at 800, 1600 and 3200 mg/kg orally by gavage. Signs observed were decreased body tone, poor grooming, prostration, ptosis, abnormal stance, piloerection, exophthalamus, diarrhea, salivation, hypersensitivity and chromaturia. None of the rats died at 800, 1600 or 3200 mg/kg.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 610 mg/kg bw
Based on:
test mat.
Mortality:
None of the rats died at 1000 mg/kg, two died at 1600 mg/kg, eight of ten died at 3200 mg/kg and ten of ten died at the 4000 mg/kg level.
Clinical signs:
Clinical signs of toxicity observed during the study included salivation, hypersensitivity, decreased activity, decreased bodytone. diarrhea, piloerection, exophthalmus, abnormal stance and gait, dried exudate around oral cavity, ptosis, poor grooming, chromodacryorrhea, semiprostation and cyanosis.
Body weight:
No effects on body weights were seen
Gross pathology:
Necropsy of those animals dying on study revealed congested lungs, hemorrhajes in the stomach mucosa and thymus/ Discoloured and distended stomach and intestines were also observed. No visible lesions were observed in teh remaining animals at terminal necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the results from the Acute Oral Toxicity Study in rats, the calculated acute oral LD50 for the test substance was determined to be 2610 mg/kg
Executive summary:

In the dose ranging finding study, four fasted animals, two per sex, were administered the test article at 800, 1600 and 3200 mg/kg, orally by gavage. Signs observed were decreased body tone, poor grooming, prostation, ptosis, abnormal stance, piloerection, exophthalmus, diarrhea, salivation, hypersensitivity and chromaturia. All rats survived.

In the acute oral toxicity study, the test substance was administered orally to five groups of ten rats at 1000, 1600, 2500, 3200 and 4000 mg/kg. None of the animals died at 1000 mg/kg, two died at 1600 mg/kg, four of ten died at 2500 mg/kg, eight of ten died at 3200 mg/kg and ten of ten died at 4000 mg/kg.

Clinical signs of toxicity observed during the study inclided salivation, hypersensitivity, decreased activity, decreased body tone, diarrhea, piloerection, exophthalmus, abnormal stance, abnormal gait, dried exudate around the oral cavity, ptosis, poor grooming, semiprostation and cyanosis. Necropsy of those animals dying on the study revelaed congested lungs, discoloured and distended stomach and intestines, hemorrhages in the stomach mucosa and the thymus. No visible lesions were observed in the remaining animals at terminal necropsy.

Based upon the results from the acute oral toxicity study in rats, the calculated acute oral LD50 for the test substance was determined to be 2610 mg/kg.