Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15-FEB-2005 to 06-APR-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 405 “Acute Eye Irritation / Corrosion”, adopted April 24, 2002. Commission Directive 2004/73/EC, B.5. “Acute Toxicity: Eye 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.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye 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 / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
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 11 weeks (male) 11 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. 97 Female Nos. 98 and 99.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1 g (per animal)
Duration of treatment / exposure:
1, 24, 48 and 72 hours (0.1 g (per animal), the treated eyes were not rinced after instillation)
Observation period (in vivo):
evaluation at 1, 24, 48 and 72 hours after instillation.
Number of animals or in vitro replicates:
three
Details on study design:
TREATMENT
The eyes of the animals were examined one day prior to test item administration.
Animals with overt signs of ocular injury or irritation which may have interfered with the interpretation of the results were not used in the test.
On the day of treatment, 0.1 g of Tosylfuranosid was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test item. The right eye remained untreated and served as the reference control. The treated eyes were not rinsed after instillation.
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 1- and 24-hour examinations, the test was completed using the two remaining animals.

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 ocular reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004, at approximately 1, 24, 48 and 72 hours after instillation.
When present, corrosion and/or staining of conjunctivae, sclerae and cornea by the test item were recorded and reported.
Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, CH-4153 Reinach/Switzerland).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
Opacity
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Remarks:
Opacity
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritant / corrosive response data:
EYE IRRITATION SCORES – ASSESSMENT ACCORDING TO EEC GUIDELINES

Evaluated intervals Corneal Opacity Iris Conjunctivae Redness Conjunctivae Chemosis
24 hours Not Irritating Not Irritating Not Irritating Not Irritating
48 hours Not Irritating Not Irritating Not Irritating Not Irritating
72 hours Not Irritating Not Irritating Not Irritating Not Irritating

Any other information on results incl. tables

VIABILITY/MORTALITY AND CLINICAL SIGNS

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

IRRITATION

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.33 for reddening and 0.00 for chemosis for all animals, respectively.

No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.

Slight to moderate reddening of the conjunctivae was noted one hour after treatment and slight reddening persisted up the 24-hour examination in all animals.

Slight swelling (chemosis) of the conjunctivae was observed at the observation performed one hour after instillation in two animals.

Slight to moderate reddening of the sclerae was present in all animals one hour after treatment and slight reddening was still observed up to the 24- or 48-hour examination in two of these animals, respectively.

Slight ocular discharge was noted in two animals one hour after treatment.

No abnormal findings were observed in the treated eye of any animal 72 hours after treatment, the end of the observation period for all animals.

COLORATION

Grey remnants of the test item were observed in the eye or conjunctival sac of all animals one hour after treatment.

CORROSION

No corrosion of the cornea was observed at any of the reading times.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Following evaluation of the experimental data according to the Commission Directive 2001/59/EC Tosylfuranosid is classified as "not irritating" to rabbit eye.
Executive summary:

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

The left eye of each animal was exposed to the test item by instilling 0.1 g of Tosylfuranosid into the conjunctival sac. The treated eyes were not rinsed after instillation. Corneal, iridic, conjunctival and scleral irritation was evaluated at 1, 24, 48 and 72 hours after instillation. The primary irritation score was calculated to reflect and classify the irritant potential of the test item.

The single instillation of Tosylfuranosid into the conjunctival sac caused mild to moderate, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and were no longer evident 72 hours after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations.

No staining of the cornea, sclera or conjunctivae nor corrosion by the test item was observed.

The Primary Eye Irritation Score for Tosylfuranosid was 0.33 (the maximum attainable score is 13.0).

Following evaluation of the experimental data according to the Commission Directive 2001/59/EC Tosylfuranosid is classified as "not irritating" to rabbit eye.