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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment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

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

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.: B002JG2
- Physical state: colorloss crystals/white crystalline powder
- Storage: in the dark

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, 7950 Biberach
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: males 265 ± 6.8 g, females 207 ± 9.1 g
- Housing: 5 animals per cage, type DK III cages (Firma Becker), without bedding
- Diet: ad libitum, Kliba rat/mouse laboratory diet (Klingentalmühle AG, CH-4303 Kaiseraugst)
- Water: ad libitum

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:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass and steel structure)
- Exposure chamber volume: 55 L
- Method of holding animals in test chamber: the animals were in placed in tubes and with their snouts in the inhalation chamber
- Source and rate of air: 1500 L/h
- Due to appropriate measures, the supply air adjusted itself to the same temperature that was found in the centrally air-conditioned laboratories. The exposure apparatus was in the air-conditioned rooms so that the temperature inside it was 19 - 25°C . There were no deviations from this specification that would have had any adverse effects on the test results.
- System of generating particulates/aerosols: a dust aerosol was generated by means of a dosing-wheel dust generator (Gericke/BASF).The concentration adjustment was achieved by variable rotation of the dosing wheel.
- By means of an exhaust air system the pressure ratios in the inhalation system were adjusted in such a way that the amount of exhaust air was about 10% lower (excess pressure). This ensured that the mixture of test substance and air was not diluted with laboratory air in the breathing zones of the animals.
- Method of particle size determination: a sample was taken after 30 min of exposure. A pre-weighed glass fibre disk and particle filter were placed in the impactor (Stack Sampler Mark III, Andersen). A 9 L sample was taken by means of pump. The contents of the preimpactor as well as on the walls of the impactor and the probed deposited were determined.

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric determination of the concentration of the inhalation atmosphere, with a Mettler HL52. The pre-weighed filter was placed in a filtration device. By means of a vacuum air pump a sample of the airborne concentration was taken. The filters were weighed afterwards. The dust concentration was calculated form the difference between the clean and used filter.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

2.2 mg/L

No. of animals per sex per dose:

5

Control animals:

other: air control

Details on study design:

- Duration of observation period following administration: 14 days
- The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings were recorded several times during exposure and at least once on each workday in the observation period. A check for dead animals was made daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

The dose-response relationship was analysed by means of the binomialtest (Wittig, H.: Mathematishe Statistik 1974, Page 32-35).
The calculation of the particle size distribution was determined in accordance to mathematical evaluation methods for particle measurements (Silverman, L.: Particle Size Analysis in Industrial Hygiene, 1971, p. 235-259)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.2 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

1 out of 10 animals died on day 1.

Clinical signs:

other: - During exposure: attempts to escape, reddish nasal secretion, accelerated breathing, salivation. - After exposure: reddished crusted orbital margins (blood test positive), accelerated breathing up to thoracic respiration, urine-smeared anogenital region

Body weight:

- Mean body weight male animals: 265 g at study start, 309 g after 14 days
- Mean body weight female animals: 207 g at study start, 239 g after 14 days

Gross pathology:

- Animal that died: acute hemorrhagic pneumonia
- Sacrificed animals: no effects observed

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Conclusions:

Under the conditions of this test, the LC50 was determined to be >2.2 mg/L.

Executive summary:

Five Wistar rats per sex were exposed in a study performed according to OECD 403 study to 2.2 mg/L air dust aerosol of the substance. After an observation period of 14 days surviving animals were necropsied. Several clinical signs were observed during and after exposure, but all surviving animals were without symptoms after the 13th observation day. Only 1 animal died after exposure. The LC50 was determined to be >2.2 mg/L air.