Pseudoephedrine

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: Comparable to guideline study with acceptable restrictions (no GLP)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(adopted 1981)

Deviations:

no

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

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: Dr. K. Thomae GMBH, D-7950 BIBERACH, Germany
- Weight at study initiation: 171-199 g
- Age: 8-9 weeks
- Fasting period before study: 16 hours, water still ad libitum
- Housing: 5 animals per cage in stainless steel wire mesh 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:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle (w/v): 10.00, 6.81, 4.64, 3.16
- Amount of vehicle: 10 mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL

Doses:

316, 464, 681, 1000 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 workday. Check for moribund and dead animals twice each each workday and once on holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 3/5 dead animals in the 1000 mg/kg dose group

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 464 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 464 - <= 1 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The results were estimated from the mortality rates. No clear dose-response effect was observed.

Mortality:

Male:
1000 mg/kg bw: 3/5
681 mg/kg bw: 0/5
464 mg/kg bw: 0/5
316 mg/kg bw: 0/5

Female:
1000 mg/kg bw: 1/5
681 mg/kg bw: 1/5
464 mg/kg bw: 2/5
316 mg/kg bw: 0/5

Clinical signs:

other: Male: 1000 mg/kg bw: dyspnea, apathy, excitation, staggering, tremors, twitching, piloerection and a poor general state. 681 mg/kg bw: dyspnea, excitation, staggering and poor general state. Additionally apathy, tremors, twitching and piloerection. 464

Gross pathology:

Necropsy showed general congestive hyperemia. Comparative necropsy of sacrified animals showed no abnormalitites.

Any other information on results incl. tables

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

Dose (mg/kg bw)	1000	681	464	316
Males
Beginning of the test	183	197	193	199
2 days	183	202	203	216
7 days	224	244	246	255
13 days	256	283	276	295
Females
Beginning of the test	180	190	171	177
2 days	175	186	172	186
7 days	198	213	188	200
13 days	212	230	197	210