(1R)-2-{[2-(4-aminophenyl)ethyl]amino}-1-phenylethanol hydrochloride

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: Study conducted to GLP and OECD/EC guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(1R)-2-{[2-(4-aminophenyl)ethyl]amino}-1-phenylethanol hydrochloride

EC Number:

700-425-8

Cas Number:

521284-22-0

Molecular formula:

C16H21ClN2O

IUPAC Name:

(1R)-2-{[2-(4-aminophenyl)ethyl]amino}-1-phenylethanol hydrochloride

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8-11 Weeks
- Weight at study initiation: 155-187g
- Fasting period before study: 16-19 hours
- Housing: IVC cages, type III H, polysulphone; Altromin saw fibre bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 degrees C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10x /hr
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- water
- Amount of vehicle (if gavage): 10mL/kg bodyweight

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

Doses:

2000, 300, 50 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: day 1 (prior to dosing) and days 8 & 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

200 mg/kg bw

Mortality:

100% mortality was observed at 2000 and 300 mg/kg 1-2 minutes post dosing, 0% mortality at 50 mg/kg

Clinical signs:

clonic convulsions and opisthotonos were associated with all mortalities along with lateral recumbency, kyphosis and half eyelid closure in the high dose group.

Clonic convulsions, opisthotonos, prone position, piloerection were seen at up to 30 minutes post-dose in 2 of the 6 animals treated at 50 mg/kg, with much reduced clinical signs (such as slight piloerection, prone position) seen in the other 4 animals. nosigns of toxicity were seen from 1d until the end of the observation period in any of the animals.

Body weight:

Body weight gain was normal for the surviving animals in this study.

Gross pathology:

No significant findings for animals dosed at 50 mg/kg.
Animals dosed at 2000 mg/kg had residual test item in the stomach.
Animals dosed at 300 mg/kg had stomachs filled with liquid and bloody spots in the brain.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose after single oral administration to female rats observed over 14 days was:
LD50 cut off (rat) = 200 mg/kg body weight.