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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from secondary literature

Data source

Reference
Reference Type:
secondary source
Title:
Repeated dose oral toxicity study of the test chemical
Author:
UNEP Publications
Year:
1994
Bibliographic source:
OECD SIDS, 1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Chronic repeated dose oral toxicity study was performed to evaluate the toxic nature of the test chemical .
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Indigo Blue
- Molecular formula: C16H10N2O2
- Molecular weight: 262.267 g/mol
- Substance type: Organic
- Physical state: No data
- Impurities (identity and concentrations): No data

Test animals

Species:
rat
Strain:
other: Albino
Details on species / strain selection:
No data
Sex:
male/female
Details on test animals and environmental conditions:
No data

Administration / exposure

Route of administration:
oral: feed
Details on route of administration:
No data
Vehicle:
other: Feed
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with diet at dose levels of 0, 0.25, 1.0 or 3.0 % (0, 100, 400, 1200 mg/kg/day)

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Diet
- Concentration in vehicle: 0, 0.25, 1.0 or 3.0 % (0, 100, 400, 1200 mg/kg/day)
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
2 years
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
0, 0.25, 1.0 or 3.0 % (0, 100, 400, 1200 mg/kg/day)
No. of animals per sex per dose:
Total: 160 males and 160 females
0 mg/Kg/day: 80 males and 80 females
100 mg/Kg/day: 25 males and 25 females
400 mg/Kg/day: 25 males and 25 females
1200 mg/Kg/day: 25 males and 25 females
Control animals:
yes, concurrent vehicle
Details on study design:
No data
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. Appearance and behavior of test rats, mortality

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations: No data

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: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

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: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. Hematocrit and hemoglobin values

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. Bilirubunuria

URINALYSIS: Yes
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data

OTHER: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, any gross changes in the organs or viscera attributable to the test material were noted

HISTOPATHOLOGY: Yes
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
Appearance and behavior of the test rats were generally comparable to those of the controls.
Mortality:
no mortality observed
Description (incidence):
No mortality was observed in the treated rats
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
At the 3% level (1200 mg/Kg/day), food consumption was significant lower than controls for the first six months but comparable to controls during the remainder of the study
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Significantly lower hematocrit and hemoglobin values in comparison with controls were obtained at all time intervals except 24 months for the males fed 3%. No such effect was noted in the females.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Bilirubinuria was observed at 24 months in male and female at 1% and females at 3%.
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
The test animals sacrificed at 52 weeks did not present any gross changes in the organs or viscera attributable to the test material. Autopsies performed on the animals which died during the second year of the study did not reveal any consistent gross changes.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Microscopic findings at two years revealed no compound related effects on the kidneys or other tissues in either sex.
Histopathological findings: neoplastic:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 200 other: mg/Kg/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects were noted at the mentioned dose level
Remarks on result:
other: No toxic effects were observed

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The No Observed Adverse Effect Level (NOAEL) for the test chemical using male and female Albino rats is considered to be 1200 mg/Kg/day.
Executive summary:

Chronic repeated dose oral toxicity study was performed to evaluate the toxic nature of the test chemical. Male and female albino rats were used in the study. The test compound was mixed with diet and used at dose levels of 0, 0.25, 1.0 or 3.0 % (0, 100, 400, 1200 mg/kg/day). The rats were treated for 2 years. The treated animals were noted for clinical signs, mortality, chenges in food consumption, hematology, blood chemistry, gross pathology and histopathology. Appearance and behavior of the test rats were generally comparable to those of the controls. No mortality was observed in the treated rats. At the 3% level (1200 mg/Kg/day), food consumption was significant lower than controls for the first six months but comparable to controls during the remainder of the study. Significantly lower hematocrit and hemoglobin values in comparison with controls were obtained at all time intervals except 24 months for the males fed 3%. No such effect was noted in the females. Bilirubinuria was observed at 24 months in male and female at 1% and females at 3%. The test animals sacrificed at 52 weeks did not present any gross changes in the organs or viscera attributable to the test material. Autopsies performed on the animals which died during the second year of the study did not reveal any consistent gross changes. Microscopic findings at two years revealed no compound related effects on the kidneys or other tissues in either sex. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for the test chemical using male and female Albino rats is considered to be 1200 mg/Kg/day.