(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-OL

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-03-28 to 2007-04-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study performed according to OECD Guideline 405 (Acute Eye Irritation / Corr and EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion) without deviation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Remarks:

Certificate issued by the Swiss GLP monitoring authorities

Test material

Test material information

Constituent 1

Reference substance name:

(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol

EC Number:

605-076-4

Cas Number:

156928-09-5

Molecular formula:

C6H10O3

IUPAC Name:

(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study reports): T002675, TIC876
- Physical state: liquid
- Appearance: colorless to yellowish liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 603T-1
- Expiration date of the lot/batch: 2007-12-19
- Purity test date: no data
- Purity: 97.76%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature
- Stability under test conditions: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: test item was applied undiluted as it was delivered by the sponsor

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: 3 male and 3 female young adult New Zealand White Rabbits; Harland Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst, The Netherlands; Postbus 6174, NL-5960 AD Horst, The Netherlands
- Age at study initiation: 11-12 weeks for males; 11-13 weeks for females
- Weight at study initiation: 2082-2271 g
- Housing: standard laboratory conditions; individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 batch no.08/07 were provided for gnawing.
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch 01/07), ad libitum
- Water (e.g. ad libitum): Füllinsdorf community tap water, ad libitum
- Acclimation period: 5 days, under laboratory conditions after health examination. Only animals without any visual signs of illnes were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): approximately 10-15
- Photoperiod (hrs dark / hrs light): 12/12, automatically controlled light cycle. Music was played during the daytime light period.

IN-LIFE DATES: From: 2007-04-02 To: no data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): test item was applied undiluted

Duration of treatment / exposure:

single application

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48, 72 hours, as well as 7 days after administration.

Number of animals or in vitro replicates:

3 (1 male, 2 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not performed

SCORING SYSTEM:
- The eye reactions were assessed according to the numerical scoring system listed in the Commission Directive 2004/731EC, April 29, 2004. Scleral reddening and ocular discharge were also assessed.

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

: redness

Basis:

animal #4

Remarks:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

conjunctivae score

Remarks:

: redness

Basis:

animal #5

Remarks:

mean

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Results 3

Irritation parameter:

conjunctivae score

Remarks:

: redness

Basis:

animal #6

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: same score- all 3 animals

Results 5

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: same score- all 3 animals

Results 6

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable - score 0

Irritant / corrosive response data:

- No abnormal findings in the cornea or iris of any animal at any time.
- A slight to moderate reddening of the conjunctivae was noted in all animals 1 hour after instillation, and persisted up to 48 hours in the male and 72 hour in the females.
- Slight to moderate swelling of the conjunctivae was noted at the 1 hour observation that persisted to 24 hours.
- All animals had slight to moderate reddening of the sclera, 1-48 hours in the male, to 72 hours in the females, and slight to moderate discharge was present 1 to 24 hours after instillation in all animals.
- No abnormal findings were observed in the treated eye of any animal 7 days after treatment, the end of the observation period for all animals.

Other effects:

VIABILITY/MORTALITY
- No clinical signs of systemic toxicity were observed, and no mortality occurred during the study.

COLORATION
- No staining of the treated eyes by the test item was observed.

CORROSION
- No corrosion of the cornea was noted at any of the observation times.

BODY WEIGHTS
- The body weights of all rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

Eye Irritation Scores - Individual Values
Animal Number	Sex	Evaluation Interval	Corneal Opacity	Area of Corneal Opacity	Iris	Conjunctivae		Sclera
						Redness	Chemosis
4	M	1 hour	0	0	0	1	2	1
5	F		0	0	0	1	2	1
6	F		0	0	0	1	2	2
4	M	24 hours	0	0	0	1	1	1
5	F		0	0	0	2	1	2
6	F		0	0	0	1	1	2
4	M	48 hours	0	0	0	1	0	1
5	F		0	0	0	1	0	1
6	F		0	0	0	1	0	1
4	M	72 hours	0	0	0	0	0	0
5	F		0	0	0	1	0	1
6	F		0	0	0	1	0	1
4	M	7 days	0	0	0	0	0	0
5	F		0	0	0	0	0	0
6	F		0	0	0	0	0	0
* Examinations were performed at the specified times after instillation of the test item.

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the reffered classification(Commission Directive 2001/59/EC of August 06, 2001), T002675 is considered to be "not irritating" to the rabbit eye.