3,9-bis(2,6-di-tert-butyl-4-methylphenoxy)-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane

Repeated dose toxicity: oral

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

Test material information

Constituent 1

Reference substance name:

3,9-bis(2,6-bis(1,1-dimethylethyl)-4-methylphenoxy)-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane

IUPAC Name:

3,9-bis(2,6-bis(1,1-dimethylethyl)-4-methylphenoxy)-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane

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.