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

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose 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:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

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

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hino Breeding Center, CHARLES RIVER LABORATORIES JAPAN, INC.
- Numbers and sex of animal received: 32 females and 32 males
- Age: at arrival: 5 weeks; at administration initiation: 6 weeks
- Weight range at arrival: males 119.2 - 136.9 g (Allowable range: 100 - 150 g); females 93.2 - 106.8 g (Allowable range: 70 - 120 g)
- Acclimation: The duration of quarantine is 5 days after the arrival and the duration of assimilation is 7 days (including that of the quarantine).
- Housing: cage stainless steel (W226 x D346 x H198 mm), individually breeding

ENVIRONMENTAL CONDITIONS
- Temperature: 23.5 - 24.4°C (measured) (allowable range: 21 - 27°C)
- Humidity: 51.1 - 64.9% (measured) (allowable range: 35 - 75%)
- Ventilation: 10 - 20 / hour
- Lighting: 7 - 19 o'clock lighting

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

Oral administration (gavage oral administration) was performed using a disposable syringe fitted with a gastric tube for rat. The administration solution was used after well stirring with a magnetic stirrer.
It was administered once a day for 28 days at a time between 8:34 to 12:56 (allowable range: 8:00 to 14:00).

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5%CMC-Na aqueous solution

Duration of treatment / exposure:

28 days

Frequency of treatment:

everyday

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

100 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

300 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

3 dose groups plus control
control: 10
100 mg/kg bw: 5
300 mg/kg bw: 5
1000 mg/kg bw: 10

Control animals:

yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

For all groups no special toxicological impact has been observed.

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Effect levels

Key result

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

clinical signs

mortality

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

For all groups no special toxicological impact has been observed. From these results, the NOEL for repeated dose toxicity are considered to be 1000 mg/kg/day.

Executive summary:

The test substance was repeatedly administered at 0 (control), 100, 300 and 1,000 mg/kg to male and female rats Cri: CD (SD) (SPF) everyday for 28 days to observe changes in the function and morphology of the body and their toxicity and recovery ere examined. In the control group, only vehicle (0.5 %(w/v) CMC-Na aqueous solution) was administered. The number of animals in each group was 5 males and 5 females, and in the control group and 1,000 mg / kg group, 14 days recovery group ( male and female, 5 animals/group each)) were designed.

As a result, all examination items, general clinical observation, functional observation examination, body weight, food consumption, hematological examination, blood biochemistry examination, urinalysis, organ weight, pathological anatomical examination and pathological examination, no changes were found due to the administration of the test substance.

Therefore, the no observed effect level (NOEL) of 3,9-dibenzyl-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane 3,9-dioxide

under this test condition was judged to be 1,000 mg/kg body weight for male and female each.