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: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-10-16 to 2016-10-29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147

Version / remarks:

November 24, 2000 as this in line with OECD 402

Deviations:

not specified

Remarks:

in line with OECD 402

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute 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
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: the test item was applied as a suspension and stable in the vehicle

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item preparation for the test group was produced shortly before administration by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer.
- Final dilution of a dissolved solid, stock liquid or gel: 40 g/100 mL

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/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: male animals approx. 8 weeks, female animals approx. 12 weeks before acclimatization period
- Weight at study initiation: males: 232.8 +/-5.63, females 208.8 +/-10.16
- Housing: single housing in makrolon cage, type III in fully air-conditioned rooms
- 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 (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: about 40 cm²
- % coverage: at least 10 %
- Type of wrap: The test item was covered with an air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 5 mL/kg bw
- Concentration: 40 g/100 mL

Duration of exposure:

24 h

Doses:

one (limit) dose of 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation. Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter. A check for any dead or moribund animals was made at least once each workday. Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

Statistics:

No statisitcal analysis necessary, calculations were performed using Microsoft Excel 2010.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality occurred.

Clinical signs:

No systemic clinical signs were observed during clinical examination.

Body weight:

The body weight of all male animals and three out of five female animals increased within the normal range throughout the study period. One female animal showed stagnation of body weight during the first week, but gained weight in a normal range during the second week. Another female showed stagnation of body weight during the whole observation period. Due to the fact that stagnation or slight loss of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Other findings:

- Other observations: No local effects were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test item (as suspension in corn oil Ph.Eur.). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days. Neither clinical signs nor local skin effects or mortality were observed in the animals. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg body weight.