Quinine

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

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.

Data source

Reference

Reference Type:

publication

Title:

Toxicity studies with quinine hydrochloride.

Author:

Colley, J. C., Edwards, J. A., Heywood, R. and Purser, D.

Year:

1989

Bibliographic source:

Toxicology. 54:219-226

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In this study the effects of quinine hydrochloride on neo-natal development was assessed in Sprague-Dawley rats. Twenty-five time-mated rats were allocated to each of the 4 groups to receive dosages of 0, 50, 100 and 200 mg/kg per day. The compound was administered by oral gavage during days 6-15 of gestation. Aqueous solutions for administration were prepared freshly each day. The animals were observed daily and were weighed at intervals of up to 4 days. Food and water consumption were recorded. On day 20 of gestation, all animals were killed and litter parameters recorded. Half of the foetuses from each litter were preserved for visceral examination by serial sectioning and half for staining with alizarin red and subsequent skeletal examination. Structural changes among offspring were classified in order of severity and/or rarity, as malformations, anomalies and variants. Litter data were analysed statistically using non-parametric methods.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Test material form:

not specified

Details on test material:

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

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Water (e.g. ad libitum): Aqueous solutions for administration were prepared freshly each day- Diet (e.g. ad libitum): Spratt's Laboratory Animal Diet No. 2ENVIRONMENTAL CONDITIONS- Temperature (°C): 20°C (+- 2°C)- Humidity (%): 50 % (+- 5%).- Photoperiod (hrs dark / hrs light): 12-h light/dark schedule

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:DIET PREPARATION- Rate of preparation of diet (frequency): The compound was administered by oral gavage during days 6-15 of gestation. Aqueous solutionsfor administration were prepared freshly each day.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

oral gavage during days 6-15 of gestation

Frequency of treatment:

each day

Duration of test:

After 20 days of gestation animals were killed and examined

No. of animals per sex per dose:

Twenty-five time-mated rats were allocated to each of the 4 groups to receive dosages of 0, 50, 100 and 200 mg/kg per day.

Control animals:

yes

Examinations

Maternal examinations:

The animals were observed daily and were weighed at intervals of up to 4 days. Food and water consumption were recorded.

Fetal examinations:

- Skeletal examinations: Yes: [half per litter] - Visceral examinations: Yes: [half per litter]

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yesDetails on maternal toxic effects:Among parent animals, treatment at 100 mg/kg per day and to a greater extent at 200 mg/kg per day, was associated with clinical signs of salivation and localized fur loss. There was markedly increased water consumption. A slight reduction in weight gain during the dosing period was recorded. These findings of maternal toxicity did not affect the incidence of malformations or in utero survival as indicated by litter size and pre- and post-implantation losses.

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

ca. 100 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects. Remark: Up to 100 mg/kg per day. Slight effects on the foetuses were observed at the high dosage of 200 mg/kg per day. Details on embryotoxic / teratogenic effects:Effects among offspring that were observed were confined to the group receiving 200 mg/kg per day and comprised a slight but significant (p < 0.05) reduction in litter and mean foetal weights and slightly increased incidence of visceral and skeletal anomalies. There was also a significantly increased incidence of foetuses with variant sternebrae at 200 mg/kg per day which is an indication of slight skeletal immaturity and was probably correlated with the lower mean foetal weight at this dosage. Slight differences in abnormality data at 50 and 100 mg/kg per day were considered to be unrelated to treatment and within this investigation, 100 mg/kg per day was regarded at the no-effect level for pre-natal development.

Effect levels (fetuses)

Dose descriptor:

NOEL

Effect level:

ca. 100 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

changes in litter size and weights

skeletal malformations

visceral malformations

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The no effect level of the read across substance quinine hydrochloride for prenatal development is 100 mg/kg per day. According to this, the no-effect level of quinine is 89.9 mg/kg bw. Furthermore, it could be concluded that quinine is not teratogenic.

Executive summary:

In this study published by Colley et al., 1989 the rat embryo toxicity of quinine hydrochloride was tested after oral application. In this study, pregnant rats received daily oral doses of quinine hydrochloride at dose levels of 0, 50, 100 and 200 mg/kg from the 6th to 15th day of gestation. In the rat embryo toxicity study there was no effect on the incidence of gross foetal changes at the dosages investigated. Slight effects on the foetuses were observed at the high dosage of 200 mg/kg per day. The no effect level of quinine hydrochloride for pre-natal development is 100 mg/kg per day. In contrast, clear effects on the parent females were observed at both 100 and 200 mg/kg per day. From this study it could be concluded that quinine hydrochloride is not teratogenic even at doses that cause marked maternal effects.