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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to recommended guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Husbandry
Animal health: Only animals in acceptable health condition were used for the test. It was certified by the veterinarian.
Number of animal room: 243/al
Housing: 3 animals I cage
Cage type: Ill. type polypropylene/polycarbonate
Bedding: laboratory bedding
Lighting period: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30-70%

Water Supply
The animals received tap water as for human consumption, ad libitum, from 500 ml bottle.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Doses:
The acute toxic class method was started at the dose level of 2000 mg/kg in female animals (n=3).
The test was continued at the dose level of 200 mg/kg in female animals (n=3) and then the test was repeated at the same dose level in male animals (n=3).
No. of animals per sex per dose:
3
Control animals:
no
Statistics:
No statistical analysis was performed.

Results and discussion

Preliminary study:
The acute toxic class method was started at the dose level of 2000 mg/kg in female animals (n=3): all animals died.
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD100
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD0
Effect level:
ca. 200 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD0
Effect level:
ca. 200 mg/kg bw
Based on:
test mat.
Mortality:
All treated animals died after the treatment at the dose level of 2000 mg/kg. Death of animals occurred 4 hours, 10 minutes and 62 minutes after the application, respectively. Decreased activity, tremor, convulsions, ventral position and severe dyspnoea were observed immediately before the death.
Clinical signs:
In dose group of 2000 mg/kg the following clinical symptoms were observed: decreased activity (3/3), tremor (2/3) on the head, convulsions (2/3) on the upper part of the body, ventral position (2/3), squatting position (3/3), piloerection (2/3), dyspnoea (3/3). The onset of symptoms was 5-10 minutes after the application. In dose group of 200 mg/kg, female animals were symptom-free during the entire observation period. Male rats showed slight activity decrease (3/3), squatting position (2/3), piloerection (3/3) 1-2 hours after the treatment with the same dose and became symptom-free on the next day.
Body weight:
The mean body weight and body weight gain changed in a similar manner that expected of untreated animals of the same age and strain.
Gross pathology:
Dead animals
In the female dose group of 2000 mg/kg, point-like haemorrhages (No.: 4697,4720) and reddish mottled colour (No.:4726) were observed in the lungs. The liver was dark red in animal No.: 4720 and congestive in another one (No.:4726). In animal No.: 4720 hyperaemic (reddish) mucous membrane was found in the stomach and the wall of the intestines was edematous. This lately alteration was noticed in animal No.: 4726, too.

Surviving animals
In the male dose group of 200 mg/kg, pulmonary emphysema (No.: 4602,4618) and pinprick-sized (No.: 4599) haemorrhages were found in the lungs. In the female dose group of 200 mg/kg, pulmonary emphysema (No.: 4692,4754) and pinprick-sized haemorrhages (No.: 4740) were detected in the lungs. Besides, pale liver (No.: 4754) and a slight hydrometra (No.: 4740) occurred in this group.
In summary, macroscopic alterations related to the toxic effect of the test item were not found either in the dead or in the surviving animals.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 value of the test item Venlafaxin 2nd Intermediate was estimated between 200 mg/kg and 2000 mg/kg body weight.