Quinine

Carcinogenicity

Description of key information

The read across substance quinine sulphate is not carcinogenic in this test system.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Link to relevant study records

Reference

Endpoint:

carcinogenicity

Remarks:

other: injected intravaginally

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The 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:

Each mouse was injected intravaginally twice a week with 0.1 ml of the test substance dissolved or suspended in gum tragacanth. Injection was made by Luer-type tuberculin syringe to the end of which was attached a record-needle adaptor. A single, initially sterile, syringe and adaptor was used for each treatment group on each occasion that treatment was given. Mice were examined post mortem between 14th & 20th month of the experiment.

GLP compliance:

not specified

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Age at study initiation: 5-6 week old - Housing: They were housed 5 to a cage in zinc boxes- Diet (e.g. ad libitum): fed Diet 41 B- Water (e.g. ad libitum): ad libitum

Route of administration:

other: injected intravaginally

Vehicle:

other: gum tragacanth

Duration of treatment / exposure:

Number of injections: 80 (twice a week)

Frequency of treatment:

twice a week with 0.1 ml of the test substance dissolved in gum tragacanth (80 injections)

Remarks:

Doses / Concentrations:0.1 ml of 0.3 % Quinine sulphate solutionBasis:nominal conc.

No. of animals per sex per dose:

20 animals for quinine sulphate 0.3%, 30 animals for vehicle control, 30 animals for untreated control and 20 animals for positive control (7,12-dimethylbenz(a)anthracene)

Control animals:

yes

Positive control:

20 animals for positive control with 0.3% 7,12-dimethylbenz(a)anthracene (DMBA)

Observations and examinations performed and frequency:

Post mortem examination for tumour

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see table) HISTOPATHOLOGY: No

Clinical signs:

not examined

Mortality:

not examined

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

see table

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

Neoplasms and Hyperplastic Lesions of Corpus Uteri, Cervix Uteri, Vagina and Perineal Skin:75% of the mice in the positive control group (treatment with DMBA) developed malignant tumours of the vagina and/or perineal skin. No mice developed genital tract tumours after intravaginal injection of quinine sulphate or gum tragacanth. Quinine sulphate is not carcinogenic.Incidence of tumours at other sites:In the post mortem examination between 14th & 20th month of the experiment 6 of 19 animals developed lung adenoma or adenocarcinoma and 2 of the 19 animals developed malignant lymphoma or reticulin cell sarcoma after treatment with quinine sulphate. However, 9 of 20 animals in the untreated control group developed lung adenoma or adenocarcinoma and 3 of the 20 animals developed malignant lymphoma or reticulin cell sarcoma. 6 of 24 animals in the gum tragacanth group developed lung adenoma or adenocarcinoma and 2 of the 24 animals developed malignant lymphoma or reticulin cell sarcoma.

Relevance of carcinogenic effects / potential:

No neoplasms and hyperplastic lesions of Corpus Uteri, Cervix Uteri, Vagina and Perineal Skin in mouse arose in response to quinine sulphate.

Neoplasms and Hyperplastic Lesions of Corpus Uteri, Cervix Uteri, Vagina and Perineal Skin

		Deaths with and without hyperplastic or neoplastic genital lesion* Time of death (months)
Test substance		0-4	4-6	6-8	8-10	10-12	12-14	14-16	16-18	18-20	Total
No treatment	with tumour	-	-	-	-	-	-	-	-	1(A)	1(A)
	without tumour	2	3	-	-	2	1	-	8	13	29
Gum tragacanth (Vehicle control)	with tumour	-	-	-	-	-	-	-	-	-	0
	without tumour	3	-	2	-	1	-	2	5	17	30
DMBA (positive control)	with tumour	-	4(C)	11(C)	-	-	-	-	-	-	15(C)
	without tumour	1	2	2	-	-	-	-	-	-	5
Quinine sulphate	with tumour	-	-	-	-	-	-	-	-	-	0
	without tumour	-	-	-	-	1	-	10	9	-	20

* A-Corpus uteri and uterine horns, B-Cervix uteri, C-Vagina + perineal skin

Conclusions:

The read across substance quinine sulphate is not carcinogenic in this test system.

Executive summary:

In the publication of Boyland et al., 1966 the carcinogenicity of the read across substance quinine sulphate is shown. The experiment was started with 20 female mice 5-6 week old. Each mouse was injected intravaginally twice a week with 0.3 % quinine sulphate. During the monitoring up to 20 month or till the mice died none of the animals developed tumour at the site of the injection. In this study quinine sulphate did not show carcinogenic activity. We conclude that quinine is not carcinogenic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Species:

mouse

Justification for classification or non-classification

From the results if the read across substance quinine sulphate it can be conclude that quinine is not carcinogenic and does not need to be classified.

Additional information

In the publication of Boyland et al., 1966 the carcinogenicity of the read across substance quinine sulphate is shown. The experiment was started with 20 female mice 5-6 week old. Each mouse was injected intravaginally twice a week with 0.3 % quinine sulphate. During the monitoring up to 20 month or till the mice died none of the animals developed tumour at the site of the injection. In this study quinine sulphate did not show carcinogenic activity. We conclude that quinine is not carcinogenic.

Justification for selection of carcinogenicity via dermal route endpoint:
The study is not done according to OECD guideline, but it is a well documented publication.