Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is not done according to OECD guideline, but it is a well documented study.

Data source

Reference
Reference Type:
publication
Title:
Mutagenicity studies with x-ray-contrast Media, analgesics, antipyretics, antirheumatics and some other pharmaceutical drugs in Bacterial, Drosphila and Mammalian test systems.
Author:
King, M. T., Beikirch, H., Eckhardt, K., Gocke, E. and Wild, D.
Year:
1979
Bibliographic source:
Mutat Res. 66(1):33-43

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test was performed according to the method of Schmid, 1976 with male and female NMRI mice, weighing about 30 g. Usually, 4 mice were used for each of 3 doses and controls. Doses were selected on the basis of previous toxicity experiments ranging from non-toxic to approximate lethal doses. Test compound was administered either i.p. or by gavage as solutions. They were given twice at 24 h apart; 6 h after the second dose the animals were killed by cervical dislocation. Bone-marrow smears were then prepared and stained with May-Gruenwald and Giemsa stains. A total of 1000 polychromatic erythrocytes were analyzed for each animal. For calculating the significance of results the tables of Kastenbaum and Bowman (Kastenbaum et al., 1976) were used. For positive control experiments various mutagens were administered, and representative data have been reported (Wild, 1978).
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): Quinine dihydrochloride
- other: obtained from EGA-Chemie GmbH and Co. KG, Stemhelm/Albuch, Germany

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 30 g

Administration / exposure

Route of administration:
other: intraperitoneal application and oral application (gavage)
Duration of treatment / exposure:
6 h after second dose
Frequency of treatment:
twice at 24 h apart
Doses / concentrations
Remarks:
Doses / Concentrations:
0.5 mmoles/kg
Basis:
nominal conc.
No. of animals per sex per dose:
4 mice (female and male)
Control animals:
yes

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls valid:
not applicable
Negative controls valid:
not specified
Positive controls valid:
yes

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The result of the micronucleus test in NMRI mice was negative after intraperitoneal and oral application. Thus, quinine dihydrochloride can be considered not genotoxic.
Executive summary:

In the study published by King et al., 1979 the genotoxicity of quinine dihydrochloride was determined with the mirconucleus test in NMRI mice. Quinine hydrochloride was given twice at 24 h apart (0.5 mmoles/kg). The micronucleus test in NMRI mice were negative. Thus, Quinine dihydrochloride can be considered as not genotoxic.