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Toxicological information

Repeated dose toxicity: oral

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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.