Registration Dossier

Administrative data

Description of key information

The no-observable-effect-level (NOEL) of the test substance in dogs via capsule administration for a period of 3 months was determined to be 2000 mg/kg/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 December 1995 to 30 May 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study in accordance with an internationally recognised test method
Guideline:
other: FDA (United States Food and Drug Administration): Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food, 1986, Appendix II page 19 "Subchronic Oral Toxicity Studies"
GLP compliance:
yes
Limit test:
no
Species:
dog
Strain:
Beagle
Sex:
male/female
Route of administration:
oral: capsule
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily/7 days per week
Remarks:
Doses / Concentrations:
0, 20, 200, 2000 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
4
Control animals:
other: Control animals were administered the same number of gelatin capsules as administered to the high-dose animals.
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:

BODY WEIGHT: Yes / No / No data
- Time schedule for examinations: Pretest, weekly during treatment and terminally (after fasting).

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: pretest and termination
- Dose groups that were examined:

HAEMATOLOGY: Yes / No / No data
- Time schedule for collection of blood:
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- Animals fasted: Yes / No / No data
- How many animals:
- Parameters checked in table [No.?] were examined.

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

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

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

OTHER:
Dose descriptor:
NOEL
Effect level:
2 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No mortality or adverse effects
Critical effects observed:
not specified
Conclusions:
Based on the parameters examined in this study, the no-observable-effect-level (NOEL) of test substance via capsule administration to Beagle dogs for a duration of 3 months is 2000 mg/kg/day.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
Study duration:
subchronic
Species:
dog

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

After 3 months of treatment, selected organ/body weight and organ/brain weight ratios were calculated. Complete gross post mortem examinations and histopathological valuation of selected tissues were conducted on all animals. None of the parameters, including mortality, physical observations, body weights and food consumption, hematology, clinical chemistry, ophthalmology, urinalysis, organ weight data and macroscopic and microscopic examination revealed any indication of adverse effects due to administration of the test substance.

Justification for classification or non-classification

No significant toxic effects of relevance to human health were observed at any of the dose concentrations used in a 90 -day repeat dose study on the dog.