6,8-Dioxabicyclo[3.2.1]octan-4-one, (1S,5R)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 Oct. - 07 Nov. 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

JUSTIFICATION FOR PERFORMING AN IN VIVO STUDY: The in vitro study report (Harlan Cytotest Cell Research GmbH, 2014a) concluded the test item to be corrosive to skin. However, this result is related to the specific physico-chemical properties (aprotic polar solvent forming multiphasic systems with water) of the test substance and false positive results in in vitro tests are expected. Therefore, the result is considered to be borderline (inconclusive) and it was recommended by Harlan Cytotest Cell Research GmbH testing facility to perform an in vivo study to obtain a reliable classification.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 24 April 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

MHRA, UK GLP Monitoring Authority

Test material

Test material information

Constituent 1

Reference substance name:

(1S,5R)-6,8-dioxabicyclo[3.2.1]octan-4-one

EC Number:

807-130-4

Cas Number:

53716-82-8

Molecular formula:

C6H8O3

IUPAC Name:

(1S,5R)-6,8-dioxabicyclo[3.2.1]octan-4-one

Details on test material:

- Name of test material (as cited in study report): Cyrene™- Analytical purity: 99%- Expiration date of the lot/batch: 30-Sep-2015- Storage condition of test material: At room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.55 or 2.74 kg
- Housing: individually housed in suspended cages
- Diet: 2930C Teklad Global Rabbit diet, Harlan Laboratories UK Ltd., Oxon, UK ; ad libitum
- Water: drinking water, ad libitum
- Acclimation period: at least five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): at least fifteen changes
- Photoperiod (hrs dark / hrs light): 12/12The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL- Amount(s) applied: 0.5 mL- Concentration: 100%

Duration of treatment / exposure:

Initial test: 3 min, 1 h and 4 h
Confirmatory test: 4 h

Observation period:

72 hours. Reading time points: 1, 24, 48 and 72 h

Number of animals:

2, male

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: The cotton gauze patch, to which the test substance was applied, was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.
REMOVAL OF TEST SUBSTANCE
- Washing: Any residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: One patch was removed at each of three time points.
SCORING SYSTEMDraize classification scheme

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No evidence of skin irritation was observed during this study. At all reading time points all scores were "0". No corrosive effects were noted.

Other effects:

- Other adverse local effects: No evidence of skin irritation was noted in any test animal following 3-minute, 1-hour or 4-hour application.
- Other adverse systemic effects: No adverse changes in body weight gain.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In the in vivo skin irritation study, conducted according to OECD Test Guideline 404 and in compliance with GLP, the test material was concluded to be not irritating to skin.