Pseudoephedrine hydrochloride

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: Non-GLP, comparable to guideline study. Available as unpublished report. Restrictions in design and/or reporting but otherwise adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(adopted 1981)

Deviations:

no

Principles of method if other than guideline:

According to BASF-internal standard: Five Wistar rats per sex per dose were exposed once by oral gavage to the test substance in water. After an observation period of 14 days, animals were necropsied.

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: (+)- pseudoephedrin-hydrochlorid

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: Mean weight of different test groups 171-199 g
- Fasting period before study: 16 hours
- Housing: 5 animals per cage in stainless steel wire mesh cages type DK-III (Becker & Co., Castrop-Rauxel, FRG)
- 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)
- Air changes (per hr): Fully air-conditioned rooms

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

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 workday and once on holidays.
- Necropsy of survivors performed: yes

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: 0/5, 0/5, and 3/5 dead animals in the 464, 681 and 1000 mg/kg dose group, respectively

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 464 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2/5, 1/5, and 1/5 dead animals in the 464, 681 and 1000 mg/kg dose group, respectively

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2/10, 1/10, and 4/10 dead animals in the 464, 681 and 1000 mg/kg dose group, respectively

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 and 681 mg/kg bw: dyspnea, apathy, excitation, staggering, tremors, twitching, piloerection and a poor general state. Clinical signs were absent within two days. 464 mg/kg bw: males were excited. Clinical sign was absent within two days. 316 mg

Gross pathology:

Necropsy of animals that died showed general congestive hyperemia. 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

Interpretation of results:

harmful

Remarks:

Migrated information

Conclusions:

Under the conditions of the performed test the LD50 was determined to be ca 1000 mg/kg bw for male animals and 464 mg/kg/bw for female animals.

Executive summary:

Five Wistar rats per sex per dose were exposed to 316, 464, 681 or 1000 mg/kg bw of the test substance dissolved in water via oral gavage. After an observation period of 14 days the surviving animals were necropsied. No dose response relationship was observed regarding mortality. Only males (3/5) of the high dose died within the observation period. 0, 2, 1, and 1 out of 5 female animals died of the 316, 464, 681, and 1000 mg/kg bw dose group, respectively. Dyspnea, apathy, excitation, staggering, tremors, twitching, piloerection and a poor general state were observed in both male and female animals. In the surviving animals these clinical signs were absent within two days. Animals that died showed general congestive hyperemia. No abnormalities were detected in sacrificed animals. The LD50 was determined to be ca. 1000 mg/kg bw for male animals and ca. 464 mg/kg/bw for female animals. The LD50 for male and female rats combined was determined to be ca. 1000 mg/kg bw.