5,7-Di-t-butyl-3-[3,5-dimethyl-4-[(1,3,7,9-tetra-t-butyl-5-methyl-5H-benzo[d][1,3,2]benzodioxaphosphocin-11-yl)oxy]phenyl]-3H-benzofuran-2-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-07-05 to 2016-09-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF 8147

Version / remarks:

2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

5,7-Di-t-butyl-3-[3,5-dimethyl-4-[(1,3,7,9-tetra-t-butyl-5-methyl-5H-benzo[d][1,3,2]benzodioxaphosphocin-11-yl)oxy]phenyl]-3H-benzofuran-2-one

EC Number:

817-187-7

Cas Number:

1803088-15-4

Molecular formula:

C54 H73 O5 P

IUPAC Name:

5,7-Di-t-butyl-3-[3,5-dimethyl-4-[(1,3,7,9-tetra-t-butyl-5-methyl-5H-benzo[d][1,3,2]benzodioxaphosphocin-11-yl)oxy]phenyl]-3H-benzofuran-2-one

Details on test material:

- State of aggregation: Solid / white
- Storage Condition: room temperature under light exclusion

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature; under light exclusion ; no direct sunlight

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals, approx. 10 weeks
- Weight at study initiation: animals were of comparable weight (+/- 20 %)
- Fasting period before study: at least 16 hours
- Housing: individual housing
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 30 - 70 %
- Air changes: approx. 10 per hr
- Photoperiod: 12 / 12 hrs dark / hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40 g/100 mL
- Amount of vehicle: 5 mL/kg bw
- Justification for choice of vehicle: Good homogeneity in corn oil

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

DOSAGE PREPARATION: The test item preparation for each test group was produced shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer. The homogeneity of the test item preparation during application was ensured by stirring with a magnetic stirrer.

CLASS METHOD
- Rationale for the selection of the starting dose: starting dose of 2000 mg/kg bw was chosen, because the test item was not expected to be acutely toxic.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (2 x 3) females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter. Individual body weights were determined shortly before administration (day 0), weekly thereafter and on the last day of observation
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Calculations were performed using Microsoft Excel 2010 and checked with a calculator.

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 occurred in both administration groups.

Clinical signs:

No clinical signs were observed during clinical examination.

Body weight:

The body weights of the test groups increased throughout the study period withing the normal range.

Gross pathology:

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, 2000 mg/kg of the test item (preparations in corn oil Ph.Eur.) were administered by gavage to two test groups of three fasted Wistar rats each (6 females). No mortality occurred and no clinical signs were observed. The body weights increased within the normal range throughout the study period. There were no macroscopic pathological findings at the end of the observation period. The acute oral LD50 was calculated to be greater than 2000 mg/kg body weight.