Ephedrine

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other: Non-GLP, similar to guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment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

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

According to BASF-internal standard: Five Sprague-Dawley rats per sex per dose were exposed once by oral gavage to the test substance in 5% aquaous CMC solution. After an observation period of 14 days, animals were necropsied.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ephedrine

EC Number:

206-080-5

EC Name:

Ephedrine

Cas Number:

299-42-3

Molecular formula:

C10H15NO

IUPAC Name:

2-(methylamino)-1-phenylpropan-1-ol

Details on test material:

- Name of test material (as cited in study report): (-)-ephedrin, wasserhaltig

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Willi Gassner, Sulzfeld
- Age at study initiation: ± 12 weeks
- Weight at study initiation: animals had comparable weights (mean ± 10 g)
- Fasting period before study: 16 hours
- Housing: 5 animals per cage, V-II-A steel wire mesh cages (Becker & Co., Castrop-Rauxel)
- Diet: Herilan, MRH-Haltung; H. Eggermann KG, 3260 Rinteln, ad libitum
- Water: ad libitum demineralized water on workdays, and ad libitum tap water on free days
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26
- Humidity (%): 45 - 75
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5% aqueous solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2.15, 3.16, 4.64, 6.81, 10% (w/v)
- Amount of vehicle: 10 mL/kg

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
- Frequency weighing: Weighing per group: 1st weighing before exposure, 2nd weighing on the 2nd - 4th day after exposure, 3rd weighing on the 7th day after exposure, and the 4th weighing on the 13th day after exposure.
- Frequency of observations: Recording of signs and symptomps was performed less than 15 min, 15 min, 30 min, 1 h, 2 h, 4 h and 5 h after exposure and after that daily. 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 died as soon as possible.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 681 mg/kg bw

Based on:

test mat.

Mortality:

- No mortality observed in animals exposed to 215 mg/kg.
- 1 out of 10 animals died exposed to 316 mg/kg within 1 day (male rat).
- 1 out of 10 animals died exposed to 464 mg/kg within 7 days (male rat)
- 6 out of 10 animals died exposed to 681 mg/kg within 1 day (3 male and 3 female rats)
- 9 out of 10 animals died exposed to 1000 mg/kg within 1 day (5 male and 4 female rats)

Clinical signs:

other: - Dyspnea, agitation, rough fur and a poor general state were observed in animals exposed to 215 mg/kg. - Dyspnea, apathy, agitation, staggering, spastic gait, rough fur, exsiccosis, salivation and a poor general state observed in animals exposed to 316 m

Gross pathology:

- Animals that died: acute hyperaemia of the heart, multiple spots in the lungs which were almost always observed in combination with blood and partial emphysema
- Sacrified 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. 681 mg/kg bw.

Executive summary:

Five Sprague-Dawley 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 0.5% aqueous carboxymetyl cellulose solution, via oral gavage. After an observation period of 14 days the surviving animals were necropsied. Several clinical signs were observed such as dyspnea, apathy, agitation, lying in an abnormal position, staggering, atony, trembling, twitching, rough fur, exsiccosis, salivation, blood in saliva, difficulty breathing, and a poor general state. Acute hyperemia of the heart and lung effects were observed in animals that died. No abnormalities were detect in sacrificed animals. The LD50 was determined to be ca. 681 mg/kg bw.