Pseudoephedrine 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other: Non-GLP, OECD guideline study, available as unpublished report.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:

1987

Report date:

1987

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:

no

Test material

Test material information

Constituent 1

Reference substance name:

Pseudoephedrine hydrochloride

EC Number:

206-462-1

EC Name:

Pseudoephedrine hydrochloride

Cas Number:

345-78-8

Molecular formula:

C10H15NO.ClH

IUPAC Name:

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

Details on test material:

- Name of the test substance used in the study report: (+)-Pseudoephedrine hydrochloride
- Appearance: white chrystals

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, Germany
- Weight at study initiation: 281 ± 7.8 g (males); 193 ± 5.62 g (females)
- Age at study initiation: ca. 8 - 9 weeks
- Housing: 5 animals per cage in stainless steel cages (Type D III)
- Diet: Kliba-Labordiat Ratte/Maus A 343 10 mm pellet, Fa. Klingentalmuhle AG, CH-4303 Kaiseraugst, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: at least 1 week

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

Administration / exposure

Route of administration:

inhalation: dust

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 (Glas-Steel-Construction, BASF AG) (animals were sitting in a tube with the snout rising into the inhalation chamber.
- Exposure chamber volume: 55 L
- Source and rate of air: Compressed air (1500 L/h), air for dilution (1500 L/h)
- System of generating particulates/aerosols: A Dust-Air-mixture was generated with a rotating brush generator (TH - Karlsruhe/BASF). Adjustment of concentration was performed by means of variable rotation of the rotating brush generator and by variable piston setting.
- Method of particle size determination: At least 30 minutes after beginning of the study, an air sample of 30 L was taken and the particles sizes were analysed by means of a Stack Sampler Mark III (Andersen ) and gravimetrical determination.
- Temperature, humidity, pressure in air chamber: 19-25°C, excess pressure (outlet air was 10% less than inlet air)

TEST ATMOSPHERE
- Brief description of analytical method used: air sample was taken from the breathing zone with a vacuum pump and filtered (MN 85/90 8f; d = 4,7 cm). A sample of one liter air (1.25 m/s) was taken every hour. The amount of dust was determined by gravimetrical analysis of the filter weight before and after sample taking.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 5.7 µm/2.6
- Rationale for the selection of the starting concentration: The concentration was chosen based on the results of the acute oral toxicity study.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

2 mg/L

No. of animals per sex per dose:

5

Control animals:

other: historical controls

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 workday. Check for moribund and dead animals at least once daily. Weighing was performed before study begin and after 7 and 14 days.
- Necropsy of survivors performed: yes

Statistics:

Calculation of particle size distribution was performed on the basis of mathematical methods for particle measurements (Silverman, L.: Particle Size Analysis in Industrial Hygiene, 1971, S. 235 - 259) in the Department of Toxicology (BASF AG).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred

Clinical signs:

other: During exposure: Nose discharge (reddish), salivation and, accelerated respiration. After exposure: Fur smeared (bloody, near head), accelerated/irregular respiration, respiratory sounds, piloerection. All symptoms were reversible within 5 (males) and 8 (

Body weight:

No difference between the weight gain of the test group and the historical control in the males. The weight gain of the females was delayed during the first week, but adjusted to a normal weigt gain during the second week post exposure (details see table 1 "Any other information on results incl. tables")

Gross pathology:

No abnormalities observed.

Any other information on results incl. tables

Table 1: Body weights of male and female animals before and after exposure to the test substance.

	Test group (2 mg/L)	Historical control
Males
Beginning of the test	281	248
7 days	305	285
14 days	341	317
Females
Beginning of the test	193	177
7 days	198	196
14 days	212	210

 

Applicant's summary and conclusion

Conclusions:

Under the conditions of the performed acute toxicity test the LC50 for inhalation was determined to be >2 mg/L air.

Executive summary:

In a OECD Guideline 403 acute inhalation toxicity study, five Wistar rats per sex were exposed to 2 mg/L air dust aerosol of the test substance. After an 14 day observation period surviving animals were necropsied. During exposure nose discharge (reddish), salivation and, accelerated respiration were observed. After exposure smeared fur (bloody, near head), accelerated/irregular respiration, respiratory sounds and, piloerection was observed. All symptoms were reversible within 5 (males) and 8 (females) days. The LC50 was determined to be >2 mg/L air.