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EC number: 202-051-6 | CAS number: 91-22-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Carcinogenicity
Administrative data
Description of key information
Quinoline is an hepatocarcinogen in rat and mouse.
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- No data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study has a lot of deficiencies (only one sex, no data on food consumption, fewer animals, a lot of deaths before the end of the study in all groups...), however, the carcinogenic effects obtained are considered valid.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Carcinogenicity study with the same principles than the EU guideline B32 however the main target was the liver.
- GLP compliance:
- not specified
- 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 - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on 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:
- once a day
- Post exposure period:
- none
- Remarks:
- Doses / Concentrations:
0.05%, 0.1% and 0.25%
Basis:
nominal in diet - No. of animals per sex per dose:
- 20 animals per groups (male only)
- 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
- 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 - Statistics:
- no data
- 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 specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- 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:
- See the tables below.
Two kinds of malignant tumor and nodular hyperplasia developed in the livers of rats treated with quinoline. Malignant tumors were hepatocellular carcinomas and hemangiosarcomas. Areas of hepatocellular carcinoma were discrete and not encapsulated, and many showed invasion of surrounding liver tissue. Most of the cords in hepatocellular carcinomas were 2 or more cells thick. The nuclei of tumor cells were prominent and were often multiple, and most tumor cells showed greater cytoplasmic basophilia than did nonneoplastic parenchymal cells. Mitotic figures were frequent in the cells of tumor tissues. Nodular hyperplasia was observed in 6 of 11 rats (54.5%) in Group 1 (0.05% of quinoline) and 4 of 16 rats (25.0%) in Group 2 (0.1% of quinoline), but not in the rats in other groups. Areas of hemangioendotheliomas or hemangiosarcomas were composed of newly formed irregular capillary structures, proliferating endothelial cells, and spindle-shaped mesenchymal cells. Tumor cells of hemangiosarcomas frequently showed mitotic figures and were irregular in size. Vascular spaces, occasionally filled with erythrocytes and hemorrhagic materials, were frequent in neoplastic lesions.
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.
Two of the 16 rats treated with 0.1% quinoline had hemorrhagic metastatic foci in the lungs. These foci showed the same histological pattern as hemangiosarcomas with large irregular nuclei and many mitotic figures. Animals treated with quinoline did not develop primary neoplasms in any organs, including s.c. or retroperitoneal tissues, other than in the liver. Hemoperitoneum or hemothorax were not seen. - Relevance of carcinogenic effects / potential:
- The carcinogenic effect are considered relevant for quinoline.
- Dose descriptor:
- conc. level:
- Effect level:
- 0.05 other: % in diet
- Sex:
- male
- Basis for effect level:
- other: based on liver tumors at each concentration.
- Remarks on result:
- other: Effect type: carcinogenicity (migrated information)
- Conclusions:
- Quinoline produces tumors in the liver of rats treated by oral route in the diet.
- Executive summary:
The effects of prolonged p.o. administration of quinoline on rat liver were examined histologically. Hepatocellular carcinomas and hemangioendotheliomas were observed in the livers of rats fed a basal diet containing 0.05, 0.10, or 0.25% quinoline for about 16 to 40 weeks.
In groups that received low concentrations of quinoline, the incidences of hepatocellular carcinomas were higher and the incidences of hemangioendotheliomas were lower than in the group that received a high concentration of quinoline.
The liver tumors induced by quinoline were classified histologically as hemangioendotheliomas or hemangiosarcomas and trabecular hepatocellular carcinomas. Typical nodular hyperplasias were occasionally seen in the livers of rats treated with quinoline.
Reference
Table 1 Changes in body and liver weights of rats treated with quinoline (mean± SD)
Concentration in diet % |
Nb of ratsa |
Mean survival (weeks) |
Body weight (g) |
Liver weight |
||
initial |
Final |
g |
% body weight |
|||
0.05 |
11 |
36.5 ± 5.0 |
168.0 ± 6.9 |
556.0 ± 64.0 |
21.3 ± 8.4 |
3.8 ± 1.4 |
0.1 |
16 |
27.3 ± 6.0 |
179.3 ± 8.0 |
451 ± 52.9 |
19.1 ± 5.2 |
4.2 ± 1.0 |
0.25 |
19 |
20.0 ± 3.8 |
178.3 ± 10.4 |
330.4 ± 62.6 |
16.1 ± 3.4 |
4.9 ± 1.0 |
control |
6 |
40.0 ± 0.0 |
178.8 ± 8.2 |
677.5 ± 64.5 |
12.3 ± 1.3 |
1.8 ± 0.0 |
arats dying within 16 weeks were not included
Table 2 Histological changes in the liver of rats treated with quinoline
Concentration in diet % |
Nb of ratsa |
Liver change |
Nb of tumor (%) |
||||
Oval cells |
Bile duct proliferation |
Fatty change |
Nodular hyperplasia |
Hepatocellular carcinoma |
Hemangioendothelioma |
||
0.05 |
11 |
± |
± |
++ |
6 (54.5) |
3 (27.2) |
6 (54.5) |
0.1 |
16 |
+ |
+ |
++ |
4 (25.0) |
3 (18.7) |
12 (75.0) |
0.25 |
19 |
++ |
+ |
+ |
0 |
0 |
18 (95.0) |
control |
6 |
- |
- |
- |
0 |
0 |
0 |
arats dying within 16 weeks were not included
Table 3 Blood analysis in rats treated with quinoline for 40 weeks (mean± SD)
Concentration in diet % |
Nb of ratsa |
RBC (x 10 000) |
WBC (x 100) |
Ht (%) |
Hb (g/dl) |
SGOT (Karmen unit) |
SGPT (Karmen unit) |
ALP (King Armstrong units) |
Ch-E (ΔpH) |
TP (g/dl) |
BUN (mg/dl) |
0.05 |
6 |
621.7± 127.7 |
81.3± 20.6 |
43.2± 9.0 |
13.1± 2.6 |
141.8± 39.5 |
40.7± 19.4 |
13.8± 3.4 |
0.2± 0.0 |
8.0± 0.5 |
11.5± 0.8 |
control |
6 |
686.8± 39.7 |
93.8± 26.0 |
46.6± 1.5 |
15.4± 0.7 |
96.8± 7.2 |
35.2± 4.3 |
10.2± 2.9 |
0.1± 0.0 |
7.7± 0.5 |
10.0± 3.5 |
RBC: red blood cell
WBC: white blood cell
Ht hematocrit
Hb haemoglobin
ALP alkaline phosphatise
BUN blood urea nitrogen
Ch-E cholinesterase
TP total protein
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- T25
- 6.11 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Several studies are available and give consistent results. None was conducted according to the standard guidelines.
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
Justification for classification or non-classification
Quinoline is currently classified as carcinogen cat 2 R45 according to the 31st ATP of the directive 67/548/EEC. This classification is not to be changed as no human data is available.
The corresponding CLP classification is carc cat 1B.
Additional information
No chronic studies and no inhalation studies of animals exposed to quinoline have been identified. The studies described below were designed to investigate the carcinogenic effects of quinoline following oral exposure, but none exposed animals for more than 40 weeks, because of early onset of tumors and early mortality.
However, the results of the available studies are consistent. Further evidences can also be obtained from the genotoxicity/mutagenicity studies: quinoline is genotoxic and mutagen in vitro and in vivo after metabolic activation. The target organ is the liver.
Quinoline is also mitogen.
From the carcinogenicity studies, it can be concluded that liver tumors and lymphomas were observed in rat and mouse (both female and male) following oral exposure. The concentrations in the diet used in these studies were between 0.05 and 0.25%. The exposure duration was between 4 and 40 weeks and the minimal duration to obtain the tumorigen activity was 12 weeks.
Male rats are more susceptible than females and the tumor profile is not identical: liver tumors are observed in male while females show lymphomas. A negative correlation between liver tumors and lymphomas has already been observed for other chemicals.
Guinea pigs and hamsters did not have tumors after a 30-week exposure to 0.2% of quinoline in diet while up to 73.3% and 80% of rat and mouse, in the same conditions had tumors, respectively.
The liver tumors were malignant (hepatocellular carcinoma). Hemangioendotheliomas (benign and malignant), which are vascular neoplasms were also observed only in the liver and are uncommon in rats and mice. A lot of early deaths observed in the studies were due to hemorrhage caused by the rupture of these tumors.
Some studies were performed to demonstrate the tumor initiator activity of quinoline in mouse following dermal application. All were consistent and showed that quinoline was indeed a tumor initiator.
The neonatal mouse model has also been applied to quinoline: the ip injection of this chemical at days 1, 8 and 15 of life induces lymphomas and liver tumors in the mouse sacrified at 52 weeks.
Starting dose T25: calculated on the basis of Hirao study showing 9/11 animals with tumors (3 with hepatocarcinomas and 6 with hemangioendotheliomas) at 0.05% (=20 mg/kg/d according to the default value given in the REACH guidance), T25 = 20*25%/(9/11) = 6.11 mg/kg/day.
There is no raw data about each animal, so the worst case assumption is considered: no animal displays both hepatocarcinoma and hemangioendothelioma, the tumour incidence may then be overestimated.
Justification for selection of carcinogenicity via oral route endpoint:
The Hirao'study is the only study which includes a dose-response evaluation.
Justification for selection of carcinogenicity via dermal route endpoint:
3 studies are available by dermal route, all were designed to evaluate the initiator properties of quinoline. They cannot be used for the risk assessment.
Carcinogenicity: via oral route (target organ): cardiovascular / hematological: lymph nodes; digestive: liver
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