Quinoline

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

combined repeated dose and carcinogenicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

no data

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Only few parameters were checked in this study which was focussed on carcinogenicity in the liver and no NOAEL is obtained. Only males are included in the study.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Carcinogenic activity of quinoline on rat liver

Author:

Hirao K, Shinohara Y, Tsuda H, Fukushima S, Takahashi M, Ito N

Year:

1976

Bibliographic source:

Cancer research 36: 329-335

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The principles are similar to the OECD guideline however fewer parameters were evaluated, and no attempt was made to find a NOAEL.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Quinoline

EC Number:

202-051-6

EC Name:

Quinoline

Cas Number:

91-22-5

Molecular formula:

C9H7N

IUPAC Name:

quinoline

Details on test material:

Supplier Nakarai Pure chemicals Co Lt (Japan)
Purity > 99.8% checked by CPG.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Clea Japan Inc
- Age at study initiation: no data
- Weight at study initiation: 160-185 g
- Fasting period before study: no data
- Housing: Individually in screen-bottomed cages
- Diet: semisynthetic basal diet composed of 75% polished rice powder, 10% casein, 4% salt mixture, 10% corn oil, and 1% vitamin mixture.
- Water: no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24°
- Humidity (%): no data
- Air changes (per hr): air-conditioned room no further data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): once a week
- Mixing appropriate amounts with (Type of food): see above
- Storage temperature of food: stoarge in a dark cold room


VEHICLE
none

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

40 weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0.05; 0.1 and 0.25%
Basis:
nominal in diet

No. of animals per sex per dose:

20 males per group

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: none
- Post-exposure recovery period in satellite groups: none
- Section schedule rationale (if not random): no data

Positive control:

none

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: no data, at least at the beginning and at the end of the study

FOOD CONSUMPTION AND COMPOUND INTAKE: no data

FOOD EFFICIENCY: no data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the study
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 6 of the low dose and of the control groups
- Parameters that were examined: Erythrocyte and leukocyte counts, the hematocrit, and the contents of hemoglobin

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at the end of the study
- Animals fasted: No data
- How many animals: 6 of the low dose and of the control groups
- Parameters that were examined: SGOT, SGPT, alkaline phosphatase, cholinesterase, cholesterol, total protein, and blood urea nitrogen

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

Rats treated with a high concentration of quinoline gained their weight slowly. Some animals treated with 0.25% quinoline died of massive intra-abdominal hemorrhage due to rupture of vascular tumors in the liver.
In general, groups treated with quinoline showed increased liver weight. (See table 1 of the ESR 7.7 Hirao 1976)
Changes in the erythrocyte and leukocyte counts, the hematocrit, and the hemoglobin content are summarized in Table 3 of the ESR 7.7 Hirao 1976. These changes in the cell counts and hemoglobin level were not significant.
The levels of SGOT and alkaline phosphatase increased slightly in rats treated with 0.05% quinoline, but the levels of SGPT, cholinesterase, total protein, and blood urea nitrogen did not change markedly.
In the nonneoplastic region of the liver, there appeared a slight to moderate degree of oval cell infiltration and proliferation of the bile ducts and also fatty degeneration of liver parenchymal cells. Occasionally, small foci were seen showing dilated sinusoidal spaces and proliferated endothelial cells with a multilayered arrangement. No cholangiofibrosis, fibrosis, or cirrhotic changes were seen in any groups.

Effect levels

Dose descriptor:

NOAEL

Effect level:

0.05 other: %

Sex:

male

Basis for effect level:

other: Based on the increase of the liver weight and slight increase of SGOT and alkaline phosphatase at this level.

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Effects on the liver are seen at the lowest concentration tested in this study so no NOAEL is obtained.

Executive summary:

A carcinogenicity study on the liver was performed with quinoline administrated to male rats in feed for 40 weeks at doses 0.05; 0.1 and 0.25%.

Some general toxicity endpoints were included in this study (clinical signs, haematology and serum chemistry). No NOAEL is obtained in this study due to increase of the liver weight and slight increase of the SGOT and alkaline phosphatase in the serum at the lowest dose.