Cyclohexanol, 1-[2-amino-1-(4-methoxyphenyl)ethyl]-, hydrochloride (1:1)

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

Venlafaxin 2nd intermediate (amino-hexanol)

IUPAC Name:

Venlafaxin 2nd intermediate (amino-hexanol)

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system 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 levels

Effect levels 1

Sex:

female

Dose descriptor:

LD100

Effect level:

ca. 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD0

Effect level:

ca. 200 mg/kg bw

Based on:

test mat.

Effect levels 3

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:

other: 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

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.