Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25-JAN-2005 to 09-MAR-2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study procedures described in this report meet or exceed the requirements of the following guidelines: OECD Guidelines for Testing of Chemicals, Section 4, number 404 “Acute Dermal Irritation / Corrosion”, adopted April 24, 2002. Commission Directive 2004/73/EC, B.4. “Acute Toxicity: Dermal Irritation/Corrosion”, April 29, 2004.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl 2,3-O-(1-methylethylidene)-5-O-[(4-methylphenyl)sulfonyl]-ß-D-ribofuranoside
EC Number:
609-920-2
Cas Number:
4137-56-8
Molecular formula:
C16H22O7S
IUPAC Name:
Methyl 2,3-O-(1-methylethylidene)-5-O-[(4-methylphenyl)sulfonyl]-ß-D-ribofuranoside
Details on test material:
Identification Tosylfuranosid
Description White solid
Stability of test item Stable under storage conditions
Expiry date 31-JUL-2005
Storage conditions At room temperature (range of 20 ± 5 °C), light protected.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST SYSTEM
Test system New Zealand White Rabbit, SPF
Rationale Recognized by the international guidelines as the recommended test system.
Source Charles River Laboratories France BP 0109 F-69592 L’Arbresle
Number of animals per test 3 (Animals of both sexes were used)
Age at treatment 12 weeks (male) 11 to 12 weeks (females)
Identification By unique cage number and corresponding ear number.
Acclimatization Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.
Allocation Male No. 63 Female Nos. 64 and 65

HUSBANDRY
Room number 0502 / RCC Ltd, Füllinsdorf
Conditions Standard Laboratory Conditions
Air-conditioned with ranges for room temperature 17-23 °C, relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.
Accommodation Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Füllinsdorf) and haysticks 4642 (batch no. 38/04, Provimi Kliba AG) were provided for gnawing.
Diet Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 68/04) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contami-nants are archived at RCC Ltd.
Water Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are ar-chived at RCC Ltd.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 g (per animal) of Tosylfuranosid was moistened with approximately 0.5 mL of purified water and applied epicutaneously to an area of approximately 16 cm2
Duration of treatment / exposure:
The duration of treatment was 4 hours.
Observation period:
After removal of the dressing and test item, the skin reactions (erythema and eschar, as well as oedema formation) were evaluated at 1, 24, 48 and 72 hours after application.
Number of animals:
three
Details on study design:
TREATMENT
Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was clipped again.
Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.
On the day of treatment, 0.5 g of Tosylfuranosid was placed on a surgical gauze patch (ca. 4 cm x 4 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.
The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
As it was suspected that the test item might produce irritancy, a single animal (one 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.

OBSERVATIONS
Viability/Mortality Daily from acclimatization of the animals to the termination of test.
Clinical signs Daily from acclimatization of the animals to the termination of test.
Body weights At start of acclimatization, on the day of application and at termination of observation.

IRRITATION SCORES
The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004, approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test item.
To allow further examination of the test site animal no. 65 was re-clipped on completion of the 72-hour examination.
If evident, corrosive or staining properties of the test item were described and recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 hour
Score:
1
Max. score:
1
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Score:
0.67
Max. score:
1
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 hours
Score:
0
Max. score:
1
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
1
Irritant / corrosive response data:
SKIN IRRITATION SCORES – ASSESSMENT ACCORDING TO EEC GUIDELINES

Evaluated intervals Erythema Oedema
24 hours Not IrritatingNot Irritating Not IrritatingNot Irritating
48 hours Not IrritatingNot Irritating Not IrritatingNot Irritating
72 hours Not IrritatingNot Irritating Not IrritatingNot Irritating
Other effects:
CORROSION: Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Any other information on results incl. tables

The Primary Irritation Score for Tosylfuranosid was 0.22 (the maximum attainable score is 8.0).

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), Tosylfuranosid is considered to be “not irritating to rabbit skin.
Executive summary:

To assess the primary skin irritation potential of Tosylfuranosid, a primary skin irritation study was performed in three (one male and two females) young adult New Zealand White rabbits.

The fur of the left flank was clipped and 0.5 g of Tosylfuranosid was applied epicutaneously to an area of approximately 16 cm2 (i.e. surgical gauze patch used for application was of approx. 4 cm x 4 cm) and then covered with a semi-occlusive dressing for approximately four hours. After removal of the dressing and test item, the skin reactions (erythema and eschar, as well as oedema formation) were evaluated at 1, 24, 48 and 72 hours after application. The primary irritation score was calculated to reflect and classify the irritant potential of the test item.

The dermal exposure to Tosylfuranosid caused very slight erythema in all animals at the 1-hour reading which persisted up to the 24-hour examination in one male and one female.

The Primary Irritation Score for Tosylfuranosid was 0.22 (the maximum attainable score is 8.0).

Following evaluation of the experimental data and based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), Tosylfuranosid is classified as “not irritating” to rabbit skin.