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Administrative data

Description of key information

The compound is not toxic in a sub-acute toxicity study. A sub chronic study does not need to be conducted since the substance is unreactive, insoluble,  not inhalable and there is no evidence of absorption in the sub-acute toxicity study.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
yes (incl. certificate)
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
28 days
Frequency of treatment:
once per day
Remarks:
Doses / Concentrations:
100, 300 and 1000 mg/kg body weight/day
Basis:
actual ingested
No. of animals per sex per dose:
5 per sex and dose and group
Control animals:
yes, concurrent vehicle
Dose descriptor:
NOEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Based on the results of this study, the no-observed-effect-level (NOEL) and no-observed-adverse-effect-level (NOAEL) were considered to be 1000 mg/kg body weight/day of 3-hydroxy-2-(3-hydroxy-2-quinolyl)-1H-inden-1-one, the highest dose tested.
Critical effects observed:
not specified

Mortality / Viability

All animals survived the scheduled treatment or recovery periods.

Clinical Signs (Daily and Weekly)

Orange discoloration of the feces, a common finding in oral studies performed with dyestuffs or colored test items, was noted at all dose levels and considered to be of no toxicological relevance.

Functional Observational Battery / Grip Strength / Locomotor Activity

There were no findings recorded during the functional observational battery at 4 weeks, including grip strength and locomotor activity.

Food Consumption / Body Weights

The mean absolute and relative food consumption of the test item-treated rats were unaffected and the mean absolute body weights and body weight gain of all treated groups compared favorably with those of the controls.

Hematology

There were no test item-related differences in the hematology parameters of males and females at any dose level.

Clinical Biochemistry

The clinical biochemistry parameters of rats at all dose levels were unaffected by treatment with the test item.

Urinalysis

The urinalysis parameters of the test item-treated animals compared favorably with those of the controls.

Organ Weights

Mildly elevated liver weights were noted at all dose levels and considered to be non-adverse, adaptive metabolic changes.

Macroscopic / Microscopic Findings

There were no treatment related macroscopic or microscopic findings.

Overall, although the slight increase in the incidence of dark yellow urine implies that a minimal absorption cannot be excluded, no discoloration was noted in any organ and there were no correlating macroscopical or microscopical findings. The treated groups showed only minimally elevated mean relative liver weights but these differences were dose-unrelated, without concomitant changes in liver-specific biochemistry parameters and without any correlating pathomorphological findings, and were considered to be unrelated to the treatment with the test item.

Based on the results of this study, the no-observed-effect-level (NOEL) and no-observed-adverse-effect-level (NOAEL) were considered to be 1000 mg/kg body weight/day of 3-hydroxy-2-(3-hydroxy-2-quinolyl)-1H-inden-1-one, the highest dose tested.

Executive summary:

Oral administration of 3-hydroxy-2-(3-hydroxy-2-quinolyl)-1H-inden-1-one to Wistar rats at doses of 100, 300 and 1000 mg/kg/day for 28 days resulted in no changes of toxicological relevance. The orange discoloration of the feces noted in all treated groups represents a typical finding in gavage studies with colored substances or dyestuffs.

Although the slight increase in the incidence of dark yellow urine implies that a minimal absorption cannot be excluded, no discoloration was noted in any organ and there were no correlating macroscopical or microscopical findings. The treated groups showed only minimally elevated mean relative liver weights but these differences were dose-unrelated, without concomitant changes in liver-specific biochemistry parameters and without any correlating pathomorphological findings, and were considered to be unrelated to the treatment with the test item.

Based on the results of this study, the no-observed-effect-level (NOEL) and no-observed-adverse-effect-level (NOAEL) were considered to be 1000 mg/kg body weight/day of 3-hydroxy-2-(3-hydroxy-2-quinolyl)-1H-inden-1-one, the highest dose tested.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral administration of 3-hydroxy-2-(3-hydroxy-2-quinolyl)-1H-inden-1-one to Wistar rats at doses of 100, 300 and 1000 mg/kg/day for 28 days resulted in no changes of toxicological relevance. The orange discoloration of the feces noted in all treated groups represents a typical finding in gavage studies with colored substances or dyestuffs.

Although the slight increase in the incidence of dark yellow urine implies that a minimal absorption cannot be excluded, no discoloration was noted in any organ and there were no correlating macroscopical or microscopical findings.

Based on the results of this study, the no-observed-effect-level (NOEL) and no-observed-adverse-effect-level (NOAEL) were considered to be 1000 mg/kg body weight/day of 3-hydroxy-2-(3-hydroxy-2-quinolyl)-1H-inden-1-one, the highest dose tested.

Justification for classification or non-classification

Oral administration of 3-hydroxy-2-(3-hydroxy-2-quinolyl)-1H-inden-1-one to Wistar rats at doses of 100, 300 and 1000 mg/kg/day for 28 days resulted in no changes of toxicological relevance.