Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
other: Data sheet (in fiscal 2010): prepared by Hazard-Data Evaluation Committee of National Institute of Technology and Evaluation based on the GLP study report obtained by Japanese Ministry of Economy, Trade and Industry.
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
- Molecular weight: 145.16
- Molecular formula: C9H7NO
- Appearance: Solid

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
- Age at study initiation of dosing: 9 weeks old
- Recovery: 0, 400 mg/kg/day

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: methylcellulose solution
Details on oral exposure:
- Male: 42 days
- Female: 42 - 46 days (from 14 days before mating to day 4 of lactation)
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (actual dose received)
Dose / conc.:
100 mg/kg bw/day (actual dose received)
Dose / conc.:
200 mg/kg bw/day (actual dose received)
Dose / conc.:
400 mg/kg bw/day (actual dose received)
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Male: Salivation (400 mg/kg/day)
Female: Salivation (400 mg/kg/day), Ptosis (400 mg/kg/day), Lacrimation (400 mg/kg/day), Soiled periurogenital fur (400 mg/kg/day)
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Male: Decrease in the body weight gain (400 mg/kg/day, tendency), Increase in the body weight gain (Recovery 400 mg/kg/day)
Female: Decrease in the body weight and body weight gain (400 mg/kg/day), Decrease in the body weight (Recovery 400 mg/kg/day, tendency), Increase in the body weight gain (Recovery 400 mg/kg/day, tendency)
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Female: Decrease in the food consumption (400 mg/kg/day)
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Female: Increase in the MCV and Plt (400 mg/kg/day), Decrease in the RBC (400 mg/kg/day, tendency), Increase in the RET (400 mg/kg/day, tendency)
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Female: Decrease in the ALP (400 mg/kg/day), Decrease in the ALT (400 mg/kg/day), Increase in Cl (400 mg/kg/day), Decrease in the Alb (400 mg/kg/day), Decrease in the A/G (400 mg/kg/day, ten
dency), Increase in the T-Cho and Ca (Recovery 400 mg/kg/day), Decrease in Cl and gamma-GTP (Recovery 400 mg/kg/day)
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
Male: Decrease in K (200 and 400 mg/kg/day), Protein positive (400 mg/kg/day)
Behaviour (functional findings):
effects observed, non-treatment-related
Description (incidence and severity):
Male: Salivation (200 and 400 mg/kg/day)
Female: Salivation (200 and 400 mg/kg/day), Decrease in the numbers of supported rearing (200 and 400 mg/kg/day), Decrease in the numbers of unsupported rearing (400 mg/kg/day)
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Male: Increase in the liver weight (Relative) (Recovery 400 mg/kg/day), Increase in the kidney weight (Absolute) (Recovery 400 mg/kg/day)
Female: Decrease in the thymus weight (Absolute and Relative) (400 mg/kg/day), Increase in the liver weight (Relative) (Recovery 400 mg/kg/day)
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Female: White mottle in the stomach (400 mg/kg/day), Red mottle in the large intestine (400 mg/kg/day)
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Female: Decrease in the incidence of vacuolar degeneration of hepatocyte (400 mg/kg/day), Erosion,
ulcer, polymorphonuclear cell infiltration and squamous hyperplasia in the forestomach (400 mg/kg/
day), Ulcer, polymorphonuclear cell infiltration and
regenerative epithelium in the glandular stomach, cecum and colon (400 mg/kg/day), Increased
extramedullary hematopoiesis in the spleen (400 mg/kg/day), Increased pigment deposition in the spl
een (Recovery 400 mg/kg/day), Atrophy of the thymus (400 mg/kg/day)
Histopathological findings: neoplastic:
no effects observed
Other effects:
not examined

Effect levels

open allclose all
Key result
Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
Key result
Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
body weight and weight gain
food consumption and compound intake
other: gastrointestinal disorder

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
For males, the NOAEL was considered to be 200 mg/kg/day, because the tendency of suppression of body weight gain was observed in the 400 mg/kg group.
For females (dams) the NOAEL was considered to be 200 mg/kg/day, because the suppression of body weight gain, lower food consumption and gastrointestinal disorder were observed in the 400 mg/kg group.
Executive summary:

Quinolin-8-ol was studied for oral toxicity in rats according to the OECD Test Guideline 422 at doses of 0, 100, 200, and 400 mg/kg. In the repeated dose oral toxicity test, salivation was observed in the 200 and 400 mg/kg groups of both sexes. However, salivation was not considered to be the treatment-related toxic effect, because it was the slight and transitory change. On functional observation battery (FOB)

test, lower numbers of supported rearing were observed in female in the 200 and 400 mg/kg groups, but it was not considered to be treatment-related suppression on CNS because there were no effects

in other parameters. Body weight gain in males receiving 400 mg/kg tended to be lower than those in the control group. Body weight gain and food consumption in females receiving 400 mg/kg were lower

than those in the control group. On urinalysis of males, low potassium excretion was noted in the 200 and 400 mg/kg groups, the number of protein-positives was increased in the 400 mg/kg group during the

administration period. However, these changes were considered to be a minor toxicological implication, because there were no histopathological lesions about renal function at the end of the administration

period. Histopathological evaluation demonstrated some gastrointestinal disorder in females receiving 400 mg/kg. There were no treatment-related findings at the recovery period. Therefore, it was concluded

that body weight and food consumption changes, and gastrointestinal disorder were corrected during the recovery period.