3,9-dibenzyl-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane 3,9-dioxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,9-dibenzyl-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane 3,9-dioxide

EC Number:

243-869-3

EC Name:

3,9-dibenzyl-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane 3,9-dioxide

Cas Number:

20544-37-0

Molecular formula:

C19H22O6P2

IUPAC Name:

3,9-dibenzyl-2,4,8,10-tetraoxa-3λ⁵,9λ⁵-diphosphaspiro[5.5]undecane-3,9-dione

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- lot No. of test material: 44216018
- Purity test date: 99.9 %

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: The test substance was put into an air-tight brown container and stored in test substance storage room at room temperature (acceptable range: from 10°C to 30°C).
- Stability under test conditions: Stable against water and heat

FORM AS APPLIED IN THE TEST: Vehicle of the dosing formulation was examined under non-GLP. Although the test substance did not dissolve and was not suspended to purified water at a concentration of 20 w/v%, the test substance was suspended to olive oil at a concentration of 20 w/v%. The condition of the formulation such as color did not change at room temperature four hours after the preparation. Therefore, olive oil was selected as a vehicle.

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan (Hino Breeding Center)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: eight or nine weeks old
- Weight at study initiation: 196.8 g for the 1st sighting study, 207.8 g for the 2nd sighting study and from 216.3 g to 222 g for the main study
- Fasting period before study: 17 to 18 hours before the administration, and for three to four hours after the administration.
- Housing: stainless steel cages with mesh-floor (260W×380D×180H mm) before the group allocation and in stainless steel cages with mesh-floor (165W×300D×150H mm) after the group allocation allocation
- Diet (e.g. ad libitum): pelleted diet (MF, lot number 181224181224, Oriental Yeast) ad libitum
- Water (e.g. ad libitum): Chlorinated water in which chloric level maintained from 3 to 5 ppm by adding sodium hypochlorite (Purelox) to Hita City supply water was used as drinking water ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 3 and 20%

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual):

- Rationale for the selection of the starting dose: Since no toxic ity information about the test substance was available, the dose level of the 1st sighting study was set at 3 00 mg/kg. The dose level of the 2nd sighting study and main study were set at 2000 mg/kg a ccord ing to the test method.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed continuously for 10 minu tes after the administration, and observed 30 minutes and three hours after the administration on the administration day. The animals were observed once in the morning from 1 to 14 days after the administration. Body weights were measured 0 (before administration), 1, 7 and 14 days after the administration.
- Necropsy of survivors performed: yes/
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality or moribundity occurred.

Clinical signs:

other: No abnormalities associated with test substance dosing were observed in the general clinical observation.

Gross pathology:

No abnormalities associated with test substance dosing were observed in necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The hazard class of the acute oral toxicity of 3,9-dibenzyl-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane 3,9-dioxide in rats under the tested conditions was classified to “unclassified” of Globally Harmonized System of Classification and Labelling of Chemicals, because no mortality or moribundity occurred and no evident toxicity was observed in the sighting study or main study at 2000 mg/kg.