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Toxicological information

Repeated dose toxicity: oral

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Administrative data

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)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Identification: Macrolex Gelb G
Physical State/Appearance: Solid / yellow powder
Purity/Concentration as Supplied: 99.1 (weight %)
Purity/Concentration for Formulation: 100%
Correction for Purity: No
Stability of Test Item in Vehicle: Assessed

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

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
Doses / concentrations
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

Results and discussion

Effect levels

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.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.