Amantadine hydrochloride

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

American Hospital Formulary Service- Drug Information

Author:

McEvoy, G.K. (ed.)

Year:

2005

Bibliographic source:

Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2005 (Plus Supplements)., p. 592

Reference 2

Reference Type:

publication

Title:

Effects of Amantadine Hydrochloride on Cleavage and Embryonic Development in the Rat and Rabbit.

Author:

Lamar JK, Calhoun FJ, and Darr AG

Year:

1970

Bibliographic source:

Abstracts of Papers for the Ninth Annual Meeting of the Society of Toxicology, Atlanta, Georgia March 15-19, 1970

Materials and methods

Principles of method if other than guideline:

Teratogenicity studies were performed in rats (0, 37, 50, and 100 mg/kg bw) by administering the drug orally on days 7-14 of gestation. Autopsy was done just before expected parturition. Resorption and number of pups per litter were determined. Gross examination of rat pups were performed and malformations were recorded.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amantadine hydrochloride

EC Number:

211-560-2

EC Name:

Amantadine hydrochloride

Cas Number:

665-66-7

Molecular formula:

C10H17N.ClH

IUPAC Name:

adamantan-1-amine hydrochloride

Details on test material:

- Name of test material (as cited in study report): Amantadine hydrochloride

Test animals

Species:

rat

Strain:

other: Virgin Holtzman rats

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

No data

Duration of treatment / exposure:

days 7-14 of gestation

Frequency of treatment:

daily

Duration of test:

Autopsy was just before expected parturition.

Doses / concentrations

Remarks:

Doses / Concentrations:
37, 50, and 100 mg/kg bw
Basis:
no data

No. of animals per sex per dose:

No data

Control animals:

yes

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes

POST-MORTEM EXAMINATIONS: Yes

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of resorptions
- Number of pups per litter

Fetal examinations:

- Gross examination of rat pups were performed and malformations were recorded.

Results and discussion

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
- Increases in resorption and decreases in the number of pups per litter were noted at 50 and 100 mg/kg bw.
- Gross examination of rat pups revealed no malformations at 37 mg/kg bw, whereas at 50 and 100 mg/kg bw malformations such as edema, malrotated hindlimbs, missing tail, stunting, and brachygnatha occured.
- Examination of cleared and alizarin stained skeletal preparations of fetuses revealed cases of absent ribs and absence of the lumbar and sacral portions of the spinal colunn in the 50 and 100 mg/kg bw groups.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

No further data available

Applicant's summary and conclusion

Conclusions:

In rats the test substance seems to be teratogenic.
Thereby, teratogenicity occured at 50 mg/kg bw/day (about 12 times the usual human dose).