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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

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 levelsopen allclose all
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
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 464 mg/kg bw
Based on:
test mat.
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:
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 mg/kg bw: males were excited.
316 mg/kg bw: no findings

Female:
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 mg/kg bw: dyspnea, excitation, staggering and poor general state.
316 mg/kg bw: no findings
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

 

Applicant's summary and conclusion