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Toxicological information

Repeated dose toxicity: oral

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1997

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
dog
Strain:
Beagle
Sex:
male/female

Administration / exposure

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
Doses / concentrations
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.

Examinations

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:

Results and discussion

Effect levels

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

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

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.