Registration Dossier

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: Acceptable, well documented publication which meets basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
The toxicologic and pharmacologic properties of amantadine hydrochloride.
Author:
Vernier VG, Harmon JB, Stump JM, Lynes TE, Marvel JP, Smith DH
Year:
1969
Bibliographic source:
Toxicol Appl Pharmacol. 1969, 15(3):642-65.

Materials and methods

Principles of method if other than guideline:
The acute toxicity after oral administration of the test substance was determined in male and female rats (Carworth Farms, CFE) over a 7-14-day observation period. At least 5 dose levels with 10 animals each were studied using narrow dose increments as aqueous solutions at a volume of 10 mL/kg bw. The LD50 and 95% confidence limits were calculated by the method of Miller and Tainter (1944), Proc. Soc. Exptl. Biol. Med. 57, 261-264.
GLP compliance:
no
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1-adamantanamine hydrochloride
- Physical state: white crystalline substance
- Analytical purity: no data

Test animals

Species:
rat
Strain:
other: Carworth Farms CFE
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 113-141 g (males); 87 - 117 g (females)

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: soluble in water (40% w/v).

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:
at least 5 dose levels using narrow dose increments (not specified)
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 7 to 14 days
Statistics:
The LD50 and 95% confidence limits were calculated by the method of Miller and Tainter (1944) Proc. Soc. Exptl. Biol. Med. 57, 261-264.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
890 mg/kg bw
Based on:
test mat.
95% CL:
761 - 1 019
Sex:
male
Dose descriptor:
LD50
Effect level:
1 275 mg/kg bw
Based on:
test mat.
95% CL:
1 095 - 1 455
Sex:
male/female
Dose descriptor:
LD50
Effect level:
890 - 1 275 mg/kg bw
Based on:
test mat.
Mortality:
All death occured 30 min to 24 hours after oral doses.
Clinical signs:
Central nervous system stimulation followed by tremors and brief clonic convulsions.
Death was preceded by signs of respiratory distress and convulsions

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU