7-Isopropyl-2H,4H-1,5-benzodioxepin-3-one

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 09 to 19, 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

Adopted 24th April 2002

Deviations:

no

Remarks:

Only two animals were tested

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Remarks:

Only two animals were tested

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on August 19, 2008/ signed on March 04, 2009)

Test material

Test material information

Constituent 1

Reference substance name:

7-(propan-2-yl)-3,4-dihydro-2H-1,5-benzodioxepin-3-one

EC Number:

700-012-2

Cas Number:

950919-28-5

Molecular formula:

C12H14O3

IUPAC Name:

7-(propan-2-yl)-3,4-dihydro-2H-1,5-benzodioxepin-3-one

Test material form:

solid

Remarks:

paste / solid block

Details on test material:

- Physical state: solid, pale yellow to yellow block, or pasty
- Stability under test conditions: no data
- Storage condition of test material: in the dark, preferably at about 4-10°C and under nitrogen.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.71-2.90 kg
- Housing: Animals were housed individually in suspended cages.
- Diet: Food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK), ad libitum.
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES: From: February 09, 2009 To: February 19, 2009.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (approximately 0.73 mg)
- For the purpose of the study, the test material was ground to a fine powder prior to application.

Duration of treatment / exposure:

No washing was done.

Observation period (in vivo):

1, 24, 48 and 72 h after instillation of test material

Number of animals or in vitro replicates:

2 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: Draize scale as described in the OECD guideline No. 405.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1 and #2

Time point:

other: Mean 24, 48 and 72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal: #1 and #2

Time point:

other: Mean 24, 48 and 72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: #1 and #2

Time point:

other: Mean 24, 48 and 72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 4

Irritation parameter:

chemosis score

Basis:

animal: #1 and #2

Time point:

other: Mean 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

- No corneal or iridial effects were observed during the study.
- Moderate conjunctival irritation was observed in all treated eyes at 1 and 24 h after treatment and minimal conjunctival irritation was observed at the 48 h.
- All treated eyes appeared normal at the 72 h observation.

Other effects:

- All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 7.3.2/1: Eye irritation response data for each animal at each observation time

Score at time point	Cornea		Iris (/2)	Conjunctivae
	Opacity (/4)	Area (/4)		Redness (/3)	Chemosis (/4)	Discharge (/3)
1 h	0 / 0	0 / 0	0 / 0	2 / 2	2 / 2	2 / 2
24 h	0 / 0	0 / 0	0 / 0	2 / 2	1 / 1	1 / 1
48 h	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
72 h	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Average 24, 48 and 72 h	0.0	0.0	0.0	1.0 / 1.0	0.3 / 0.3	0.3 / 0.3
Reversibility	-	-	-	Completely reversible	Completely reversible	Completely reversible
Average time (unit) for reversion	-	-	-	72 h	48 h	48 h

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an eye irritation study performed according to the OECD Guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted test material (approximately 0.73 mg) was instilled into the right eye of 2 male New Zealand White rabbits following a sequential testing strategy. The left eye remained untreated and served as control. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test material, and then released. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h after treatment and graded according to the Draize method.

No corneal or iridial effects were observed during the study. Moderate conjunctival irritation was observed in all treated eyes at 1 and 24 h after treatment and minimal conjunctival irritation was observed at the 48 h. All treated eyes appeared normal at the 72 h observation.

Mean individual scores at 24, 48 and 72 h after exposure for the 2 animals were 0.0 / 0.0 for cornea score; 0.0 / 0.0 for iris score; 1.0 / 1.0 for conjunctivae score and 0.3 / 0.3 for chemosis score.

Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

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