Registration Dossier

Diss Factsheets

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: Guideline study. Good description of methods, exposition system and analytical investigations.

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

Test material

Constituent 1
Reference substance name:
Pseudoephedrine hydrochloride
EC Number:
206-462-1
EC Name:
Pseudoephedrine hydrochloride
Cas Number:
345-78-8
IUPAC Name:
2-(methylamino)-1-phenylpropan-1-ol hydrochloride
Details on test material:
Name: (+)-Pseudoephedrine hydrochloride
Purity: 99-100.5%
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: SPF-Wistar/Chbb :TNOM rats from Dr. K. Thomae GMBH, D-7950 BIBERACH, Germany
- Weight at study initiation: 281 +/- 8 g (males); 193 +/- 6 g (females)
- Housing: 5 animals per cage in stainless steel cages
- Diet: Kliba-Labordiaet, Fa. Klingentalmuehle 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:
other: melange of substance dust and 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 (if not tabulated)
- Particle size distribution:
- 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
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:
Dose-response relationship:
On the basis of the binominal-test (Wittig, H.: Mathematische Statistik, 1974, page 32 -35), according to the tables of the BASF Rechenzentrums .
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
Exp. duration:
4 h
Mortality:
No mortality occurred
Clinical signs:
other: During exposition: nose discharge (reddish), salivation, accelerated respiration After exposition: fur smeared (bloody, near head), accelerated/irregular respiration, respiratory sounds, piloerection All symptoms were reversible within 5 (males) and 8 (fe
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")
Gross pathology:
No abnormalities observed.

Any other information on results incl. tables

Table 1: Body weights of male and female animals before and after administration of 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