Quinine dihydrochloride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information

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. Quinine dihydrochloride is not genotoxic.

Link to relevant study records

Reference

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.

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

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 30 g

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

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

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not applicable

Negative controls validity:

not specified

Positive controls validity:

valid

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

In the in vitro study published by Sideropoulos et al., 1984 the genotoxicity of quinine dihydrochloride was determined with the Ames test on the two Salmonella typhimurium strains TA 100 and TA 98 with and without metabolic activation. For both strains no mutations were detected up to 50 µg quinine dihydrochloride per plate. Therfore, we can conclude that quinine dihydrochloride is not genotoxic. In the study published by King et al., 1979 the genotoxicity of quinine dihydrochloride was determined with the Ames Test with and without metabolic activation. 2 tester strains of S.typhimurium designated TA98 and TA1538 as well as E.coli were used. Quinine dihydrochloride is not mutagenic to S.typhimurium tester strain TA1535 and E.coli 98 in the presence and absence of S-9 mix, but mutagenic to S.typhimurium tester strain TA98 in the presence of S-9 mix. For TA98 with metabolic activation the number of revertants increase with concentration up to 8.7 µmoles per plate. However, quinine dihydrochloride is not mutagenic without S-9 mix. Salmonella strain TA98 is a frameshift mutant derived from strain TA1538 by introducing an R factor plasmid pKM101. The strain TA98 is more sensitive to some frameshift mutagens as compared with the strain TA1538. Accordingly, quinine dihydrochloride might acts as a frameshift mutagen in Salmonella, indicating that Quinine dihydrochloride might provide genotoxic effects. Nevertheless, the in vivo micronucleus test in NMRI mice of quinine dihydrochloride is also negative. Therefore, we can conclude that quinine dihydrochloride has no mutagenic effects.

Justification for selection of genetic toxicity endpoint
The study is not done according to OECD guideline, but it is a well documented study.

Justification for classification or non-classification

In the publication of Sideropoulos et al., 1984 the result of the Ames test of quinine dihydrochloride was negativ. Furthermore, the in vivo micronucleus test in NMRI mice of quinine dihydrochloride is also negative. Therefore, we can conclude that quinine dihydrochloride has no mutagenic effects and does not need to be classified.