Lorenox™

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 - 19 March 2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP study conducted according to OECD 405 Guideline without any deviation. The substance is adequately identified, but some data on composition is missing. Therefore validation applies with restrictions.

Justification for type of information:

An in vivo study was performed for worldwide notification purposes.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

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:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2008-04-14&15 /Signed on 2008-07-16.

Test material

Test material information

Constituent 1

Reference substance name:

1,5-Cyclododecadiene, 9-methoxy-1,6,10-trimethyl-

Cas Number:

900779-74-0

Molecular formula:

C16 H28 O

IUPAC Name:

1,5-Cyclododecadiene, 9-methoxy-1,6,10-trimethyl-

Constituent 2

Reference substance name:

1,5-Cyclododecadiene, 10-methoxy-1,5,9-trimethyl-

Cas Number:

900779-83-1

Molecular formula:

C16 H28 O

IUPAC Name:

1,5-Cyclododecadiene, 10-methoxy-1,5,9-trimethyl-

Constituent 3

Reference substance name:

1,5-Cyclododecadiene, 9-methoxy-2,5,10-trimethyl-

Cas Number:

900779-84-2

Molecular formula:

C16 H28 O

IUPAC Name:

1,5-Cyclododecadiene, 9-methoxy-2,5,10-trimethyl-

Constituent 4

Reference substance name:

1,5-Cyclododecadiene, 9-methoxy-1,5,10-trimethyl-

Cas Number:

900779-85-3

Molecular formula:

C16 H28 O

IUPAC Name:

1,5-Cyclododecadiene, 9-methoxy-1,5,10-trimethyl-

Test material form:

liquid

Details on test material:

- Storage condition of test material: Room temperature

Specific details on test material used for the study:

- Date received: 10 February 2009 (Flask 1); 18 February 2009 (Flask 2)

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)
- Age at study initiation: 14-15 weeks
- Weight at study initiation: 3.10-3.57 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: Foodstuff (SDS- C15), ad libitum
- Water: Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17–23 °C
- Humidity: 30-70 %
- Air changes: ca. 15 changes per hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 02 - 19 March 2009

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

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

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 and 72 h & Days 4 to 10 following treatment, according to a numerical evaluation.

Number of animals or in vitro replicates:

3 males

Details on study design:

TREATMENT
- 0.1 mL of the 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:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

animal #1

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 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 6 days

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:

2.3

Max. score:

4

Reversibility:

fully reversible within: 5 days

Remarks on result:

probability of mild irritation

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #2

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 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 9 days

Remarks on result:

probability of weak irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

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:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of 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:

2

Max. score:

3

Reversibility:

fully reversible within: 10 days

Remarks on result:

positive indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The ocular conjunctivae reactions observed during the study have been moderate to severe and totally reversible in the three animals: a moderate redness, noted 1 hour after the test item instillation and totally reversible between day 6 and day 10, associated with a moderate to severe chemosis, noted 1 hour after the test item instillation and totally reversible between day 5 and day 8.

Other effects:

None

Any other information on results incl. tables

Table 7.3.2/1: Individual and Mean Scores for Cornea, Iris and Conjunctivae

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A9477 male	1 h	0	0	2	2
	24 h	0	0	1	3
	48 h	0	0	1	3
	72 h	0	0	1	1
	Day 4	0	0	1	1
	Day 5	0	0	1	0
	Day 6	0	0	0	0
	Total (24, 48 and 72 h)	0	0	3	7
	Mean (24, 48 and 72 h)	0.0	0.0	1.0	2.3
A9482 male	1 h	0	0	2	2
	24 h	0	0	1	1
	48 h	0	0	1	1
	72 h	0	0	1	1
	Day 4	0	0	1	1
	Day 7	0	0	1	1
	Day 8	0	0	1	0
	Day 9	0	0	0	0
	Total (24, 48 and 72 h)	0	0	3	3
	Mean (24, 48 and 72 h)	0.0	0.0	1.0	1.0
A9483 male	1 h	0	0	2	3
	24 h	0	0	2	2
	48 h	0	0	2	2
	72 h	0	0	2	2
	Day 4	0	0	1	2
	Day 7	0	0	1	1
	Day 8	0	0	1	0
	Day 9	0	0	1	0
	Day 10	0	0	0	0
	Total (24, 48 and 72 h)	0	0	6	6
	Mean (24, 48 and 72 h)	0.0	0.0	2.0	2.0

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

Under the test conditions, test item is classified in Category 2 for eye irritation according to the annex I of the Regulation (EC) No. 1272/2008 (CLP) and in Category 2A according to the GHS.

Executive summary:

In an eye irritation study conducted according to OECD 405 guideline and in compliance with GLP, 3 New Zealand White male rabbits were exposed to 0.1 mL of test item in one eye while the contralateral eye remained untreated and served as control. The lids were then gently held together for about one second in order to prevent loss of the test item. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and Days 4 to 10 following treatment and graded according to the Draize method.

 

The ocular conjunctivae reactions observed during the study have been moderate to severe and totally reversible in the three animals: a moderate redness, noted 1 hour after the test item instillation and totally reversible between day 6 and day 10, associated with a moderate to severe chemosis, noted 1 hour after the test item instillation and totally reversible between day 5 and day 8.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0, 0.0, 0.0 for cornea score; 0.0, 0.0, 0.0 for iris score; 1.0, 1.0, 2.0 for conjunctivae score and 2.3, 1.0, 2.0 for chemosis score.

 

Under the test conditions, test item is classified in Category 2 as "irritating to eyes" according to the annex I of the Regulation (EC) No. 1272/2008 (CLP) and in Category 2A according to the GHS.

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