7-oxabicyclo[4.1.0]hept-3-ylmethyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 May 2010 to 8 June 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Proprietary guideline compliant study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other 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 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

1

Reference substance name:

7-oxabicyclo[4.1.0]hept-3-ylmethyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

EC Number:

219-207-4

EC Name:

7-oxabicyclo[4.1.0]hept-3-ylmethyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

Cas Number:

2386-87-0

Molecular formula:

C14H20O4

IUPAC Name:

7-oxabicyclo[4.1.0]hept-3-ylmethyl 7-oxabicyclo[4.1.0]heptane-3-carboxylate

Specific details on test material used for the study:

- Name of test material (as cited in study report): Celloxide 2021P
- Substance type: Not documented
- Physical state: Yellow liquid
- Analytical purity: 96.48%
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Not documented
- Lot/batch No.: CELP-AD-038
- Expiration date of the lot/batch: 7th July 2010
- Stability under test conditions: Not documented
- Storage condition of test material: Stored in a sealed container, at room temperature and in the dark.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK. Ltd., Bicester.
- Age at study initiation: 8 - 9weeks old
- Weight at study initiation: Males: 242 - 277g
Females: 175 - 204g
- Fasting period before study:
- Housing: During the acclimatisation period, up to five rats of the same sex were accommodated in cages. From the day prior to dosing, each rat was housed individually in a similar cage. After completion of the Day 3 observations animals allocated to the main study were returned to group housing. Bedding was provided on a weekly basis to each cage by use of clean Aspen wood chips.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1 available freely to animals at all times.
- Water (e.g. ad libitum): Mains water was provided, ad libitum, via cage-mounted water bottles.
- Acclimation period: 7 - 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Humidity (%): 45 - 65%
- Air changes (per hr): 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

IN-LIFE DATES: From: 17 May 2010 To: 8 June 2010

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsum of the rat
- % coverage: 10% The total surface area (cm2) for each animal was calculated according to the largest animal in each group using the following formula:
Surface area (cm2) = K x body weight (g)2/3 (where K = 9) {Spector, W.S., Handbook of Biological Data, W.B. Sanders Co., 1956; 175.}

- Type of wrap if used: A dense gauze patch was placed over the treated skin and retained in place by an elasticated, open-weave, adhesive compression bandage. This was wrapped securely around the torso of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dermal test site of each rat was lightly brushed clean of any solid residues and swabbed with water-moistened cotton wool
- Time after start of exposure: Approximately 24 hours after the start of exposure

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg Dose volume 1.693 mL/kg bw adjusted for specific gravity of 1.1816 g/mL to achieve 2000 mg/kg bw dose level
- Concentration (if solution): applied as supplied without dilution
- Constant volume or concentration used: Constant volume
- For solids, paste formed: Not relevant

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

In the preliminary test, 2 test animals (1 per sex) were used.
In the definitive test, 8 animals were used (4 per sex), meaning a total of 10 animals (5 per sex) were treated in the study.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed on the day prior to dosing and on days 1, 4, 8 and 15. Clinical observations were made once within half an hour of dosing, four times within four hours of dosing, twice daily on Days 2, 3 and 4 and once daily from the fifth day of the observation period. The condition of the dermal test site was recorded following removal of the dressing on Day 2 and once daily thereafter for the duration of the study period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology. Dermal reactions assessed using standard modified Draize evaluation schema.

Statistics:

Not relevant - median lethal dose determined directly from mortality incidence.

Results and discussion

Preliminary study:

Not relevant

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths occurred during the study

Clinical signs:

other: other: There were no clinical signs of reaction to treatment. No dermal reactions were observed.

Gross pathology:

No macroscopic changes were noted at necropsy.

Other findings:

No additional information provided.

Any other information on results incl. tables

No additional information

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute median lethal dose of Celloxide 2021P to rats was found to exceed 2000 mg/kg. Based on the result of this study, the test substance does not require classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

Executive summary:

In a study conducted by Dreher (2010), the test substance, Celloxide 2021P, was investigated to determine its ability to induce dermal toxicity following a single semi-occluded topical application to the test species, male and female Wistar rats. The dorsum of a group of 5 male and 5 female rats was clipped and 2000mg/kg of the test substance was applied, undiluted, to this test area. The treated area of the dorsum was covered by a semi-occlusive dressing for 24 hours. The animals were observed for a 14 day observation period. At sacrifice on Day 15, a full necropsy was performed.

No animal died and there were no clinical signs of reaction to treatment. No abnormal dermal changes were noted at the test sites. All rats gained weight during the first and second weeks of the study, except for two females which lost weight during the second week of the study but showed an overall increase in body weight over the observation period. There were no macroscopic changes apparent at necropsy.

Under the conditions of this study, the acute median lethal dose of Celloxide 2021P to rats was found to exceed 2000mg/kg. Based on the result of this study, the test substance does not require classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.