4,7-dichloroquinoline

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from authoritative database

Data source

Reference

Reference Type:

review article or handbook

Title:

Toxicological Evaluations of the test chemical

Author:

FAO

Year:

2015

Bibliographic source:

Toxicological Evaluations of the test chemical, 2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

90 days repeated dose oral toxicity study was performed to evaluate the toxicological profile of the test chemical

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,7-dichloroquinoline-8-carboxylic acid

EC Number:

402-780-1

EC Name:

3,7-dichloroquinoline-8-carboxylic acid

Cas Number:

84087-01-4

Molecular formula:

C10H5Cl2NO2

IUPAC Name:

3,7-Dichloroquinoline-8-carboxylic acid

Test material form:

solid

Details on test material:

Name of the test chemical: 3,7-Dichloroquinoline-8-carboxylic acid
Common Name: Quinclorac
Molecular Weight: 242.0605 g/mol
Molecular Formula: C10H5Cl2NO2
Substance Type: Organic
Physical State: Solid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Wistar (Chbb=Thom) rats

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: diet

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

0, 1000, 4000 or 12 000 ppm for 3 months. Achieved test chemical intakes were 0, 77, 302 and 930 mg/kg bw per day for males and 0, 87, 358 and 1035 mg/kg bw per day for females, respectively.

Duration of treatment / exposure:

3 months

Frequency of treatment:

daily

Doses / concentrations

Remarks:

0, 1000, 4000 or 12 000 ppm for 3 months. Achieved test chemical intakes were 0, 77, 302 and 930 mg/kg bw per day for males and 0, 87, 358 and 1035 mg/kg bw per day for females, respectively.

No. of animals per sex per dose:

Groups of 10 male and 10 female Wistar (Chbb=Thom) rats

Control animals:

yes, concurrent no treatment

Details on study design:

no data available

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes / No / Not specified :
- Time schedule:
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes / No / Not specified : yes
- Time schedule: Clinical signs were observed regularly

BODY WEIGHT: Yes / No / Not specified : yes
- Time schedule for examinations: body weight were observed regularly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / Not specified : food consumption were observed reegularly
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / Not specified

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / Not specified : yes
- Time schedule for examinations: water consumption were observed regularly

OPHTHALMOSCOPIC EXAMINATION: Yes / No / Not specified : yes
- Time schedule for examinations: Ophthalmoscopy was performed on animals in the control and top-dose groups, pretest and prior to sacrifice.
- Dose groups that were examined:

HAEMATOLOGY: Yes / No / Not specified : yes
- Time schedule for collection of blood: Samples for clinical chemistry and haematology were takenon day 86.
- Anaesthetic used for blood collection: Yes (identity) / No / Not specified
- Animals fasted: Yes / No / Not specified
- How many animals:
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes / No / Not specified : yes
- Time schedule for collection of blood: Samples for clinical chemistry and haematology were taken on day 86.
- Animals fasted: Yes / No / Not specified
- How many animals:
- Parameters checked in table [No.?] were examined.

URINALYSIS: Yes / No / Not specified : yes
- Time schedule for collection of urine: Urine analysis samples were obtained on day 80.
- Metabolism cages used for collection of urine: Yes / No / Not specified
- Animals fasted: Yes / No / Not specified
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: Yes / No / Not specified
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

IMMUNOLOGY: Yes / No / Not specified
- Time schedule for examinations:
- How many animals:
- Dose groups that were examined:
- Parameters checked in table [No.?] were examined.

OTHER:

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see table) / No / Not specified : All animals were subjected to a gross pathological examination followed by a microscopic examination.

HISTOPATHOLOGY: Yes (see table) / No / Not specified: Control and top-dose animals received a full microscopic examination; for the low- and intermediate-dose groups, only lungs, liver, kidneys and gross lesions were examined.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

A initial deficit in body weight in top-dose males was associated with reduced feed consumption and, although statistically significant, was less than 10%. There were no treatment-related adverse effects in the animals of the low dose and mid dose groups

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

There were no treatment-related adverse effects in the animals of the low dose and mid dose groups. There were no treatment-related adverse effects in the animals of the low dose and mid dose groups

Food efficiency:

not specified

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

effects observed, treatment-related

Description (incidence and severity):

A number of water consumption were altered in top-dose animals indicative of potential liver and kidney toxicity. There were no treatment-related adverse effects in the animals of the low dose and mid dose groups

Ophthalmological findings:

no effects observed

Description (incidence and severity):

There were no treatment-related adverse effects in the animals of the low dose and mid dose groups

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Erythrocyte parameters were reduced in top-dose females. There were no treatment-related adverse effects in the animals of the low dose and mid dose groups

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

A number of clinical chemistry parameters were altered in top-dose animals indicative of potential liver and kidney toxicity. Plasma bilirubin was decreased dose relatedly in all male groups (Table 8), but
this is not considered to be adverse in isolation.There were no treatment-related adverse effects in the animals of the low dose and mid dose groups

Urinalysis findings:

no effects observed

Description (incidence and severity):

There were no treatment-related adverse effects in the animals of the low dose and mid dose groups

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

There were no treatment-related adverse effects in the animals of the low dose and mid dose groups

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

The only pathological findings of note were chronic interstitial nephritis and focal urothelial hyperplasia in top-dose males. There were no treatment-related adverse effects in the animals of the low dose and mid dose groups

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

The only pathological findings of note were chronic interstitial nephritis and focal urothelial hyperplasia in top-dose males.There were no treatment-related adverse effects in the animals of the low dose and mid dose groups

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

Dose descriptor:

NOAEL

Effect level:

302 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical biochemistry

clinical signs

food consumption and compound intake

gross pathology

haematology

histopathology: non-neoplastic

mortality

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

The NOAEL was 4000 ppm (equal to 302 mg/kg bw per day), based on a range of clinical chemistry and haematological changes in both sexes and interstitial nephritis and urothelial hyperplasia in males at 12 000 ppm (equal to 930 mg/kg bw per day

Executive summary:

90 days repeated dose oral toxicity study was performed to evaluate the toxicological profile of the test chemical.

Groups of 10 male and 10 female Wistar (Chbb=Thom) rats were given diets containing the test chemical dose of 0, 1000, 4000 or 12 000 ppm for 3 months. Achieved test article intakes were 0, 77, 302 and 930 mg/kg bw per day for males and 0, 87, 358 and 1035 mg/kg bw per day for females, respectively. Clinical signs, body weight, and feed and water consumption were monitored regularly. Samples for clinical chemistry and haematology were taken on day 86. Urine analysis samples were obtained on day 80. Ophthalmoscopy was performed on animals in the control and top-dose groups, pretest and prior to sacrifice. All animals were subjected to a gross pathological examination followed by a microscopic examination. Control and top-dose animals received a full microscopic examination; for the low- and intermediate-dose groups, only lungs, liver, kidneys and gross lesions were examined. and mid-dose groups. Plasma bilirubin was decreased dose relatedly in all male groups (Table 8), but this is not considered to be adverse in isolation. The NOAEL was 4000 ppm (equal to 302 mg/kg bw per day), based on a range of clinical chemistry and haematological changes in both sexes and interstitial nephritis and urothelial hyperplasia in males at 12 000 ppm (equal to 930 mg/kg bw per day