2H-Pyran, tetrahydro-3-(phenylmethyl)-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 December 2004 to 03 January 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD Guideline 405 with deviations: age at study initiation, feeding conditions not reported. These deviations do not affect the quality of the study and are not considered to be relevant. The substance is considered to be adequately characterised.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

yes

Remarks:

age at study initiation, feeding conditions not reported

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Directive n° 2004/73/EC.

Deviations:

yes

Remarks:

age at study initiation, feeding conditions not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected 2004-07-01 / Signed 2004-09-13

Test material

Test material information

Constituent 1

Reference substance name:

(3R)-3-benzyloxane

Molecular formula:

C12 H16 O

IUPAC Name:

(3R)-3-benzyloxane

Constituent 2

Reference substance name:

(3S)-3-benzyloxane

Molecular formula:

C12 H16 O

IUPAC Name:

(3S)-3-benzyloxane

Test material form:

liquid

Remarks:

clear

Details on test material:

- Physical state: Colourless translucent liquid, characteristic odour
- Storage conditions : room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome, Quartier Labaste – F40260 Linxe - FRANCE
- Weight at study initiation: 2.34-2.75 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: No data
- Water: No data
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20-21 °C
- Humidity: 30-52 %

IN-LIFE DATES: 20 December 2004 to 03 January 2005

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye serving as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted

Duration of treatment / exposure:

No washing was done

Observation period (in vivo):

Ocular examinations were performed on both right and left eyes 1, 24, 48, 72 h and Day 4 to Day 11 following treatment, according to a numerical evaluation.

Number of animals or in vitro replicates:

3 males

Details on study design:

TREATMENT
A volume of 0.1 mL of the pure test item was instilled into the conjunctival sac of one eye, the other eye remained untreated serving as control. Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: According to OECD guideline 405

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: Day 11

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: Day 7

Remarks on result:

probability of weak irritation

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: Day 8

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: Day 7

Remarks on result:

probability of weak irritation

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: Day 4

Remarks on result:

probability of mild irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Remarks on result:

probability of weak irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: Day 6

Remarks on result:

probability of mild irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: Day 5

Remarks on result:

probability of weak irritation

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: Day 4

Remarks on result:

probability of mild irritation

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: Day 7

Remarks on result:

probability of weak irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

The ocular reactions observed during the study have been slight to moderate, and totally reversible in the three animals:
- at the conjunctivae level: a moderate enanthema, noted 24 hours after the test product instillation and totally reversible between the 7th and the 9th day of the test, associated with a slight to moderate chemosis, noted 24 hours after the test product instillation and totally reversible between the 3rd and the 8th day of the test ;
- at the corneal level: a moderate opacity, registered 24 hours after the test product instillation, and totally reversible between the 5th and the 12th day of the test,
- at the iris level: a congestion, registered 24 hours after the test product instillation in 2 animals, and between the 5th and the 7th day of the test in one animal

Other effects:

None

Any other information on results incl. tables

Table 7.3.2/1: Individual and mean scores of conjunctivae, iris and cornea

Time / Animal	Cornea			Iris			Conjunctivae
							redness			chemosis
	1 (A6389)	2 (A6394)	3 (A6395)	1 (A6389)	2 (A6394)	3 (A6395)	1 (A6389)	2 (A6394)	3 (A695)	1 (A6389)	2 (A6394)	3 (A6395)
1 h	0	0	0	0	0	0	1	2	1	1	1	1
24 h	2	2	2	1	1	0	2	2	2	1	2	1
48 h	2	2	1	0	0	0	1	2	1	1	1	0
72 h	2	1	1	0	0	0	1	2	1	1	1	0
D4	2	0	0	1	0	0	1	1	1	1	1	0
D5	2	0	0	1	0	0	1	1	1	1	0	0
D6	2	0	0	1	0	0	1	0	1	1	0	0
D7	1	-	0	0	-	0	1	-	0	0	-	0
D8	1	-	-	0	-	-	0	-	-	0	-	-
D9	1	-	-	0	-	-	0	-	-	0	-	-
D10	1	-	-	0	-	-	0	-	-	0	-	-
D11	0	-	-	0	-	-	0	-	-	0	-	-
Mean 24/48/72 h	2.0	1.7	1.3	0.3	0.3	0.0	1.3	2.0	1.3	1.0	1.3	0.3

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Under the test conditions, the test substance is classified in Category 2 (H319: Causes serious eye irritation) according to the criteria of the Regulation EC No. 1272/2008 (CLP) and classified in Category 2A (irritating to eyes) according to the GHS.

Executive summary:

In an eye irritation study conducted according to OECD 405 Guideline and in compliance with GLP, test substance was instilled as supplied, into the eye of 3 New Zealand rabbits at the dose of 0.1 mL, the other eye remained untreated serving as control. The lids were then gently held together for about one second in order to prevent loss of the test substance. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and 4 to 11 days after treatment and graded according to the Draize method.  

 

The ocular reactions observed during the study have been slight to moderate, and totally reversible in the three animals:

- at the conjunctivae level: a moderate enanthema, noted 24 hours after the test product instillation and totally reversible between the 7th and the 9th day of the test, associated with a slight to moderate chemosis, noted 24 hours after the test product instillation and totally reversible between the 3rd and the 8th day of the test ;

- at the corneal level: a moderate opacity, registered 24 hours after the test product instillation, and totally reversible between the 5th and the 12th day of the test,

- at the iris level: a congestion, registered 24 hours after the test product instillation in 2 animals, and between the 5th and the 7th day of the test in one animal.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2.0, 1.7, 1.3 for cornea score; 0.3, 0.3, 0.0 for iris score; 1.3, 2.0, 1.3 for conjunctivae score and 1.0, 1.3, 0.3 for chemosis score.

 

Under the test conditions, the test substance is classified in Category 2 (H319: Causes serious eye irritation) according to the criteria of the Regulation EC No. 1272/2008 (CLP) and classified in Category 2A (irritating to eyes) according to the GHS.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.