1,4:3,6-dianhydro-2,5-di-O-octanoyl-D-glucitol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

from September 8,2009 to September 15,2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

In compliance with OECD guideline No. 404 and method B4 of Commission Directive No. 2004/73/EC (April 29, 2004) adapting to technical progress for the 29th Council Directive No. 67/548/EEC and subsequent amendments and of Council Regulation No. 440/2008 (30th May 2008) and Regulation No. 1907/2006 (REACH). (as the data is used in a read-across approach, a maximal reliability score of 2 was attributed).

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

These deviations are considered by the Study Director to have had no determinal impact on the results of the study. The study took place in accordance with the study plan.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

These deviations are considered by the Study Director to have had no determinal impact on the results of the study. The study took place in accordance with the study plan.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

700-073-5

EC Number:

700-073-5

IUPAC Name:

700-073-5

Details on test material:

Name: LAB 3822
Supplier: ROQUETTE FRERES
Batch Number: FAL 07/25
Galenic form: slightly yellowish liquid
Molecular weight (base form): about 426 g/mol
Retest date: Mar 2010
Intended use: Ind. Chemical
On 17 Jul 2007, a 26.2 kg sample of test item was received, in vials labelled "LAB 3822, batch No. FAL 07/25".
Storage conditions: Immediately upon receipt, the test item was registered, then stored at ambient temperature in accordance with the Sponsor0s instructions.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:GRIMAUD FRERES SELECTION - La Corbière - 49450 Roussay, France.
- Weight at study initiation:Between 1.9 kg and 2.3 kg at the start of the experiment.
- Housing:Observation was performed at the time of delivery of the animals and daily during the acclimatisation period. Animals were housed individually in cages of standard size. These cages were placed in an air-conditioned (15- 21°C) animal house kept at between 45 % and 65 % relative humidity (except during the cleaning slot) in which non-recycled filtered air was changed approximately 10-15 times per hour. These parameters are continuously recorded using a computerised acquisition system. The artificial day/night cycle was 12 hours light and 12 hours darkness with light on at 7.30 a.m.
- Diet (e.g. ad libitum): SDS/DIETEX STANRAB (P) SQC feed was available ad libitum.
- Water (e.g. ad libitum):Drinking water was available ad libitum in polycarbonate bottles with a stainless steel nipple. A specimen of water is sent every 6 months to IPL (Institut Pasteur de Lille-Laboratoire d'analyses de l0Allier) - Boulevard Nomazy - BP1707 - 03017 Moulins Cedex - France, for analysis.
- Acclimation period:For at least 5 days before the treatment, in the area where the experiment took place.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

0.5 mL of LAB 3822 was applied to the skin of the right flank region. The dose was expressed in mL of LAB 3822 as supplied. The standard amounts applied were not adjusted to body weight.For this purpose, approximately 24 hours before the test, the treatment region of each rabbit was carefully clipped free of fur over an area of at least 14 cm x 5 cm. Care was taken to avoid abrading the skin.
The test item was applied at the selected area on the right flank of each animal. Adjacent surfaces of non-treated skin of each animal served as a control for the trial.
The test item was placed directly on the skin, over an area of approximately 6 cm2 then covered with a gauze square of the same surface area. This gauze square was protected by a pad consisting of a semi-occlusive micro-porous and non-allergenic dressing and held in place with a supple and aerated fastening system consisting of elastic, adhesive, hypoallergenic tape. The animals were fitted with this pad for the duration of the exposure period.

Duration of treatment / exposure:

A first patch was removed after three minutes. As no skin reaction was observed, a second patch was applied and removed after one hour. As the observations at this stage indicated that exposure could be allowed to extend to four hours, a third patch was applied and removed after four hours and the responses were graded.

Observation period:

one hour, 25 hours, 49 hours and 73 hours after removal of the dressing.

Number of animals:

3 animals

Details on study design:

Three animals are required for the complete test. Animals were selected on the basis of their general conditions.
The day of application was taken as D1 of the study.
LAB 3822 was applied three times sucessively at a duration of three minutes, one hour and four hours respectively (exposure of one animal).
LAB 3822 was applied once only, at a duration of exposure of 4 hours (exposure of two additional animals).
As neither a corrosive effect or a severe irritant effect was observed after four hours exposure, the test was completed using two additional animals, each with one patch only, for an exposure period of four hours.

Results and discussion

Any other information on results incl. tables

Cutaneous irritation

The application of the test item did not induce colouration of the application site and did not interfere with grading of any skin lesion. No cutaneous lesion was observed one hour after the removal of the dressing in any animal. A slight erythema (score 1) was observed in all animals (for 4 hours exposure time) 24 hours after the removal of the dressing and in two animals 48 and 72 hours after the removal of the dressing. No cutaneous lesion persisted in any animal at the end of the monitoring period (i.e, at time 72 hours for one animal and on D8 for the two other animals).

Mean indices calculated from results obtained from each rabbit at times 24, 48 and 72 hours were:

Results of mean index:

Treatment	Animal number	Erythema	Oedema
LAB 3822	20091226 - 3 min exposure	0	0
LAB 3822	20091226 - 1h exposure	0	0
LAB 3822	20091226 - 4h exposure	1	0
LAB 3822	20091227	0.33	0
LAB 3822	20091228	1	0

Body weight (individual values)

Treatment	Animal number	day 1	day 4	day 8
LAB 3822	20091226	2.045	NE	2.271
LAB 3822	20091227	1.970	1.920	NE
LAB 3822	20091228	2.252	NE	2.380

NE:   Not evaluated

Results expressed in kg

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions adopted, LAB 3822 (Batch No. FAL 07/25) was found to be non-irritant for the skin of the rabbit.
Classification according to Directive No. 67/548/EEC and subsequent amendments and CLP Regulation No. 1272/2008:
Symbol: none is required.
Indication of danger: none is appropriate.
Risk phrase: none is applicable.

Executive summary:

Any irritant property and/or degree of corrosion of LAB 3822 (Batch No. FAL 07/25) was evaluated in the rabbit following a single semi-occluded application to intact skin in accordance with the General Requirements of O.E.C.D Guideline No. 404 (April 24, 2002) and method B4 of Commission Directive No. 2004/73/EC (April 29, 2004) adapting to technical progress for the 29th Council Directive No. 67/548/EEC and subsequent amendments and of Council Regulation No. 440/2008 (30th May 2008) and Regulation No. 1907/2006 (REACH).

Three animals were used for the study.

0.5 mL of LAB 3822 was applied on the skin. Adjacent surfaces of untreated skin served as a control for the trial.

Semi-occlusive dressings held the test item in place for 3 minutes, 1 hour and 4 hours on the skin of the first animal and for 4 hours on the skin of the two other animals.

The application of the test item did not induce colouration of the application site and did not interfere with grading of any skin lesion. Any cutaneous lesion was evaluated approximately one hour, 24, 48 and 72 hours for one animal and up to 8 days after removal of the dressing for two other animals.

Mean indices were calculated from results obtained from each rabbit at times 24, 48 and 72 hours.

Results obtained were as follows:

No cutaneous lesion was observed one hour after the removal of the dressing in any animal. A slight erythema (score 1) was observed in all animals (for 4 hours exposure time) 24 hours after the removal of the dressing and in two animals 48 and 72 hours after the removal of the dressing. No cutaneous lesion persisted in any animal at the end of the monitoring period (i.e, at time 72 hours for one animal and on D8 for the two other animals).

Treatment	Animal number	Erythema	Oedema
LAB 3822	20091226 - 3 min exposure	0	0
LAB 3822	20091226 - 1h exposure	0	0
LAB 3822	20091226 - 4h exposure	1	0
LAB 3822	20091227	0.33	0
LAB 3822	20091228	1	0

Under the experimental conditions adopted, LAB 3822 (Batch No. FAL 07/25) was found to be non-irritant for the skin of the rabbit.

Classification according to Directive No. 67/548/EEC and subsequent amendments and CLP Regulation No. 1272/2008:

Symbol: none is required.

Indication of danger: none is appropriate.

Risk phrase: none is applicable.