Bis[[R-(R*,S*)]-β-hydroxy-α-methylphenethyl)methylammonium] sulphate

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other: Non-GLP, similar to guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment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:

Bis[[R-(R*,S*)]-β-hydroxy-α-methylphenethyl)methylammonium] sulphate

EC Number:

205-154-4

EC Name:

Bis[[R-(R*,S*)]-β-hydroxy-α-methylphenethyl)methylammonium] sulphate

Cas Number:

134-72-5

Molecular formula:

C10H15NO.1/2H2O4S

IUPAC Name:

bis([(1R,2S)-1-hydroxy-1-phenylpropan-2-yl](methyl)azanium) sulfate

Details on test material:

- Name of the test substance used in the study report: (-)-Ephedrin-Sulfat

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 170-186 g, males 171-191 g
- Fasting period before study: 16 hours (water was still available)
- Housing: 5 animals per cage, stainless steel wire mesh cages, Type DK-III (Becker & Co., Castrop-Rauxel
- 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:

- Justification for choice of vehicle: The aqueous formulation corresponds to the physiologial medium.
- Concentrations used (w/v): 0.68, 1, 1.47, 2.15, 3.16, 4.64
- Administration volume (mL/kg): 10

Doses:

68.1, 100, 147, 215, 316, 464 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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. Body weight was determined before the test and at day 7, 9, and 13.
- Necropsy of survivors performed: yes; Withdrawal of food 16 hours before sacrifice with CO2; then necropsy with gross-pathological examination

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

368 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 464 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

189 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was observed within 1 day after exposure.
- No mortality observed in animals exposed to 68.1 or 100 mg/kg bw.
- 4 out of 10 animals died exposed to 147 mg/kg bw (1 male and 3 females).
- 4 out of 10 animals died exposed to 215 mg/kg bw (all females).
- 3 out of 10 animals died exposed to 316 mg/kg bw (1 male and 2 females).
- 6 out of 10 animals died exposed to 464 mg/kg bw (1 male and 5 females).

Clinical signs:

other: - Excitation and piloerection observed in male and female animals exposed to 68.1 mg/kg bw. - Dyspnea, excitation, staggering, piloerection, and a poor general state observed in male and female animals exposed to 100 mg/kg bw. - Dyspnea, apathy (male only

Gross pathology:

- Animals that died: lung: edematous, focal hyperemia.
- Sacrificed animals: no abnormalities detected.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information

Conclusions:

Under the conditions of this test, the LD50 was determined to be 189 mg/kg bw.

Executive summary:

Five Wistar rats per sex per dose were exposed, in a acute oral toxicity study similar to OECD guideline 401, to 68.1, 100, 147.0, 215, 316, and 464 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. Several clinical signs were observed such as dyspnea, apathy, excitation, abnormal position, staggering, tremors, twitching, tonus of the jaws, tonic convulsions, piloerection, exophthalmos, salivation, imbalance, and a poor general state. These effects were absent after 2 days. Upon necropsy edematous lungs and focal hyperemia were observed in animals that died. The LD50 was determined to be 189 and more than 464 mg/kg bw for females en males, respectively.