.alpha.-D-Glucopyranoside, methyl 1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-, compd. with 2-butyne-1,4-diol (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb 15- March 2, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Solvate of (2S,3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol with 2-butyne-1, 4-diol (1:1)

Cas Number:

960404-59-5

Molecular formula:

C26 H33 Cl O9

IUPAC Name:

Solvate of (2S,3R,4S,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol with 2-butyne-1, 4-diol (1:1)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

New Zealand White rabbits were supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK.; acclimatisation period of at least five days; At the start of the study the animals were in the weight range of 2.0 to 3.5 kg and
were twelve to twenty weeks old. Free access to mains drinking water and food was allowed through out the study. The temperature and relative humidity were set to achieve limits of 19 to 25 C and 30 to 70% respectively. The rate of air exchange was at least 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours of darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: distilled water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 g of the test material, moistened with 0.5 ml of distilled water was introduced under 2.5 cm X 2.5 cm cotton gauze patch

Duration of treatment / exposure:

One animal was intially treated at three sites. One patch was removed at each of these 3 times: 1 minute, one hour and 4 hours after application. The patch was removed at the indicated times and any residual material removed from the test area by gentle swabbing with cotton wool soaked in distilled water. After review of the first animal data, 2 additional animlas were treated where one patch was applied and allowed to remain for 4 hours after application.

Observation period:

Approximately one hour after removing the patch and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored.

Number of animals:

3

Details on study design:

The day before the test the rabbits were clipped free of fur from the dorsal/flank area and inspected for gross abnormalities of the epidermis. Only animals with an intact healthy epidermis are selected for the study. A suitable site on the back of the rabbit was selected as test site and 0.5 g of test material moistened with 0.5 ml of distilled water was introduced under a 2.5 cm X 2.5 cm cotton gauze patch which was secured in position with surgical tape. For animal one there were three patches which were removed 3 mintes, 1 hour and 4 hours after application. After the patchwas removed, the test sites were evaluated after 1 hour, 24, 48, and 72 hours according to the Draize classification scheme for determination of primary irritation index.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 4

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24hr 72hr

Score:

1.5

Reversibility:

fully reversible

Remarks on result:

other: mild irritant

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

The individual scores for erythema/eschar and oedema were very slight and never above a 1 for all three animals for the complete 72 hour observation period. The Draize classification scheme for determination of primary irritation index was used. Results were fully reversible.

Any other information on results incl. tables

Calculation of Primary Irritation Index and Grading of Irritancy Potential Using the Draize

Scheme: The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test

rabbits (12 values) and this total was divided by six to give the primary irritation index of the test

material.

Primary Irritation Index Classification of Irritancy

0                                   Non-irritant

>0 to2                            Mild irritant

>2 to 5                            Moderate irritant

> 5 to 8                           Severe irritant

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material produced a primary irritation index of 1.5 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. The test material did not meet the classification as irritant or corrosive according to the EU labelling regulations.