(R*,S*)-(±)-α-[1-(methylamino)ethyl]benzyl alcohol hydrochloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP non-guideline study, available as unpublished report, limitations in design and/or reporting but otherwise adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(R*,S*)-(±)-α-[1-(methylamino)ethyl]benzyl alcohol hydrochloride

EC Number:

205-153-9

EC Name:

(R*,S*)-(±)-α-[1-(methylamino)ethyl]benzyl alcohol hydrochloride

Cas Number:

134-71-4

Molecular formula:

C10 H15 N O .Cl H

IUPAC Name:

(1-hydroxy-1-phenylpropan-2-yl)(methyl)azanium chloride

Details on test material:

- Name of the test substance used in the study report: DL-Ephedrin-HCl
- Test substance No.: 86/12

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, D-7950 Biberach, FRG
- Weight at study initiation: mean group weight females 179 - 190 g, males 179 - 199 g
- Fasting period before study: 16 h
- Housing: 5 animals per cage, stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, FRG)
- Diet: ad libitum, Kliba-Labordiaet, Fa. Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland
- Water: ad libitum, tap water
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -24
- Humidity (%): 30 - 70
- Air: fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

- The aqueous formulation corresponds to the physiologial medium.
- Form of administration: solution
- Administration volume (mL/kg): 10

Doses:

215, 316, 464, 681, 1000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Signs and symptoms: Recording of signs and symptoms several times on the day of administration (at least once each working day). A check for moribund and dead animals was made twice each working day and once on public holidays.
- Necropsy of survivors performed: yes
- Pathology: Withdrawal of food 16 hours before sacrifice with CO2; then necropsy with gross-pathological examination. Necropsy of all animals that die as soon as possible.

Statistics:

Test for homogeneity: Chi-square

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

827 mg/kg bw

Based on:

test mat.

95% CL:

586 - 1 371

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 316 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

527 mg/kg bw

Based on:

test mat.

95% CL:

412 - 698

Mortality:

- No mortality observed in animals exposed to 215 mg/kg.
- 3 out of 10 animals died exposed to 316 mg/kg, within 1 day, all were female.
- 4 out of 10 animals died exposed to 464 mg/kg, within 1 day, all were female.
- 6 out of 10 animals died exposed to 681 mg/kg, within 1 day, 5 were female and 1 male.
- 9 out of 10 animals died exposed to 1000 mg/kg, within 1 day, 5 were female and 4 male.

Gross pathology:

- Animals that died: general congestive hyperemia, liver grey-brown broadened lobular periphery in some animals.
- Sacrificed animals: no abnormalities observed

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information

Conclusions:

Under the conditions of this test, the LD50 was determined to be ca. 316 and 827 mg/kg bw for female and male rats, respectively.

Executive summary:

Five Wistar rats per sex per dose were exposed in a study similar to OECD 401 to 215, 316, 464, 681 or 1000 mg/kg bw of the test substance dissolved in water via oral gavage. After an observation period of 14 days the surviving animals were necropsied. Animals that died showed general congestive hyperemia and a grey-brown broadened lobular periphery liver in some animals. No abnormalities were detected in sacrificed animals. The LD50 was determined to be ca. 316 and 827 mg/kg bw for female and male rats, respectively.