Registration Dossier

Administrative data

Description of key information

Quinoline is considered as harmful by oral and dermal route according to the Dangerous Substance Directive criteria.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study not performed according to GLP but it is similar to the OECD 401 guideline however the substance tested is poorly described.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
Study performed before the GLP creation
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Schering AG, Berlin
- Age at study initiation: no data
- Weight at study initiation: male: 110-130 g; female: 110-125 g
- Fasting period before study: yes for 16 hour
- Housing: 5 animals/ cage
- Diet: Ssniff (pellets)
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: no data

Doses:
0.10; 0.16; 0.25; 0.40 mL/kg bw
No. of animals per sex per dose:
5
Control animals:
other: yes, receiving 40 mL/kg bw of a solution of CMC at 0.5%
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no data
Statistics:
LD50 calculation based on Kärber formula and Weil method.
Preliminary study:
not relevant
Sex:
male/female
Dose descriptor:
LD50
Effect level:
0.24 mL/kg bw
95% CL:
0.18 - 0.32
Mortality:
See the table
Clinical signs:
unkempt fur, hunched posture, paleness of extremities, increased lacrymation, lethargy and ataxia of grade minimal to medium to high.
Body weight:
Body weight gain similar to the control
Gross pathology:
Sacrified animal at the end of the study:
Hyperemia of medium grade, hemorrhagic edema of the lungs of minimal grade, apparent lobular contour of the liver parenchym which was loam-coloured, swelling of the liver parenchym, punctiform hemorrhagic erosion of the glandular stomach mucous membrane, bloody stomach content depending on the dose, petechial bleeding in the non glandular mucous membrane of the stomach, minimal to medium grade hyperemia of the duodenum mucous membrane with bloody gut content depending on the dose.

Animals dead during the study:
Hyperemia of minimal to medium grade, hemorrhagic edema of the lungs of minimal grade, minimal to medium grade hyperemia of the liver with apparent lobular contour and swelling of the parenchym.
Other findings:
none

Dose (mL/kg bw)

Sex

No of animals

No of dead animals

Control

M
F

5
5

0
0

0%

0.10

M
F

5
5

1
0

10%

0.16

M
F

5
5

2
0

20%

0.25

M
F

5
5

3
2

50%

0.40

M
F

5
5

5
4

90%

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of quinoline in the rat is 262 mg/kg bw, It is considered as harmful according to the 67/548/EEC directive and toxic cat 3 according to CLP
Executive summary:

A standard acute oral toxicity method has been performed with quinoline on rat. 5 animals per sex per group were treated by quinoline doses from 0.10 to 0.40 mL/kg bw. In these conditions, the LD50 is 0.24 mL/kg corresponding to 262 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
262 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jun-Jul 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study not performed according to GLP but it is similar to the OECD 402 guideline however the substance tested is poorly described.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr A Ivanovas, Kissleg/Allgäu
- Age at study initiation: no data
- Weight at study initiation: male: 220-270 g, female: 200-245 g
- Fasting period before study: no data
- Housing: individually
- Diet: Ssniff R10 (pellets) ad libitum
- Water (e.g. ad libitum): yes
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: June To: July 1981
Type of coverage:
occlusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: back, area 5 x 7.5 cm
- % coverage: no data
- Type of wrap if used: aluminium foil and "Elastoplast"


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with lukewarm water
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3 mL / kg
- Concentration (if solution): no data
- Constant volume: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): no data
- Lot/batch no. (if required): no data
- Purity: no data
Duration of exposure:
24 h
Doses:
0.82 - 1.0 - 1.21 - 1.47 mL/kg bw
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once a day for observations, at day 1, 7 and 15 for weighing
- Necropsy of survivors performed: yes
Statistics:
Finney method
Preliminary study:
not relevant
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1.26 mL/kg bw
95% CL:
1.15 - 1.39
Mortality:
See table 1
Clinical signs:
Skin effect:
Neither erythem nor oedema was observed.
Clinical signs:
Decrease of motility, abdominal posture of pre-agony.
Body weight:
No effect on body weight gain.
Gross pathology:
No effects in the animal that died in the study.
Animals sacrified at the end of the study:
Dose 1 mL/kg: Pale discoloration of liver and kidneys, bloody aspect of the stomach and intestine content (1 female)
Dose 1.21 mL/kg: Autolysis (1 male), Pale discoloration of liver and kidneys, medium grade hyperemia of the lungs. Bloody aspect of the stomach and small intestine content (2 females)
Dose 1.47 mL/kg: Autolysis (2 males and 5 females), Pale discoloration of liver and kidneys (2 males), medium grade hyperemia of the lungs (2 males). Bloody aspect of the stomach (2 males and 3 females) and small intestine content (2 males).
Other findings:
none

Table 1: Mortality

Time

Control

0.82 mL/kg

1.0 mL/kg

1.21 mL/kg

1.47 mL/kg

Up to 6h

M
F

0/5
0/5

0/5
0/5

0/5
0/5

0/5
0/5

0/5
0/5

6-24h

M
F

0/5
0/5

0/5
0/5

0/5
0/5

0/5
0/5

0/5
0/5

24-48h

M
F

0/5
0/5

0/5
0/5

0/5
1/5

0/5
1/5

4/5
4/5

3-7 d

M
F

0/5
0/5

0/5
0/5

0/5
0/5

1/5
1/5

0/5
1/5

7-14d

M
F

0/5
0/5

0/5
0/5

0/5
0/5

0/5
0/5

0/5
0/5

Total

M
F

0/5
0/5

0/5
0/5

0/5
1/5

1/5
2/5

4/5
5/5

 %    0  0 10   30 90 
Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 of quinoline in rat is 1377 mg/kg. Quinoline is harmful in contact with skin according to the 67/548/EEC directive and according to CLP (cat 4).
Executive summary:

A standard dermal acute toxicity method has been performed with quinoline on rat. 5 animals per sex per group were treated by quinoline doses from 0.82 to 1.47 mL/kg bw. In these conditions, the LD50 is 1.26 mL/kg corresponding to 1377 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 377 mg/kg bw

Additional information

Valid LD50 are available for quinoline for oral and dermal route. Both were determined in rats, males and females. No obvious difference in susceptibility was observed between both. They were chosen as key studies because they were performed according to standard guidelines but they are too old to be compliant with GLP.

The observed clinical signs are: decreased motility, paleness of extremities

The gross pathology findings are mainly hemorrhagic aspect of the digestive tract and hyperemia of the lung.

2 studies are available via inhalation exposure however they are considered unvalid and their results are inconsistent. A new study is not deemed necessary because quinoline vapour pressure is rather low (around 10 Pa at 25°C) and the aerosol creation should not arrive in the handling conditions.


Justification for selection of acute toxicity – oral endpoint
This is the only study considered as valid.

Justification for selection of acute toxicity – dermal endpoint
This is the only study considered as valid.

Justification for classification or non-classification

Quinoline is currently classified as harmful R21/22 according to the 31st ATP of the directive 67/548/EEC. This classification is not to be changed.

The corresponding CLP classification is oral cat 3 and dermal cat 4.