D-Glucitol, 1,5-anhydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-, 2,3,4,6-tetraacetate, (1S)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2009-03-18 to 2009-03-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[(2R,3R,4R,5S,6S)-3,4,5-tris(acetyloxy)-6-(3-{[5-(4-fluorophenyl)thiophen-2-yl]methyl}-4-methylphenyl)oxan-2-yl]methyl acetate

EC Number:

617-901-5

Cas Number:

866607-35-4

Molecular formula:

C32H33FO9S

IUPAC Name:

[(2R,3R,4R,5S,6S)-3,4,5-tris(acetyloxy)-6-(3-{[5-(4-fluorophenyl)thiophen-2-yl]methyl}-4-methylphenyl)oxan-2-yl]methyl acetate

Test material form:

solid: particulate/powder

Details on test material:

- Physical state: solid
- Appearance: white powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Young adult New Zealand White Rabbit, SPF from Harlan Laboraotries B.V.
- Age when treated: 15 weeks (male), 15-16 weeks (females)
- Weight when treated: 2513 g (male), 2646 - 2878 g (females)
- Housing: standard laboratory conditions; individually housed in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing.
- Diet (e.g. ad libitum): ad libitum, pelleted standard Provimi Kliba 3418
- Water (e.g. ad libitum): ad libitum, community tap water
- Acclimation period: under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hrs light and 12 hrs dark, music during the daytime light period

IN-LIFE DATES: From: 2009-03-18 To: 2009-03-30

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

purified

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g
- Concentration (if solution): not applicable (solid)

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

at 1, 24, 48 and 72 hours after exposure (after removal of dressing, gauze patch and test item)

Number of animals:

3 (1 male, 2 females)
As it was suspected that the test item might produce irritancy, a single animal (female) was treated first. As neither a corrosive effect nor a severe irritant effect was observed after the 4-hour exposure, the test was completed using the two remaining animals for an exposure period of four hours.

Details on study design:

TEST SITE
- Area of exposure: left flank
- % coverage: 2.5 cm x 2.5 cm
- Type of wrap if used: on the day of treatment, 0.5 g of T003066 was placed on a surgical gauze patch held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restrainer bandage wrapped around the abdomen.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the dressing was removed and skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
- Time after start of exposure: 4 hours

SCORING SYSTEM: numerical scoring system listed in the Commission regulation No. 440/2008 B.4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

male 63

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

erythema score

Basis:

mean

Remarks:

female 64

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 3

Irritation parameter:

erythema score

Basis:

mean

Remarks:

female 65

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

male 63

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 5

Irritation parameter:

edema score

Basis:

mean

Remarks:

female 64

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 6

Irritation parameter:

edema score

Basis:

mean

Remarks:

female 65

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). No staining produced by the test item of the treated skin was observed. Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

- no mortality occurred
- no clinical signs were observed during the course of the study
- the body weights of all rabbits were considered to be within the normal range of variability
- no necropsy was performed at the end of the study

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001) and the criteria of the CLP Regulation (EC) No
1272/2008, T003066 is considered to be 'non-irritating' to rabbit skin.