1-(5-propyl-1,3-benzodioxol-2-yl)-1-ethanone

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 March to 14 April 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 405 without deviation.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on 10 July 2012 / signed on 30 November 2012)

Test material

Test material information

Constituent 1

Reference substance name:

1-(5-propyl-2H-1,3-benzodioxol-2-yl)ethan-1-one

EC Number:

700-902-0

Cas Number:

1370699-98-1

Molecular formula:

C12H14O3

IUPAC Name:

1-(5-propyl-2H-1,3-benzodioxol-2-yl)ethan-1-one

Test material form:

liquid

Details on test material:

- Physical state: Colourless liquid
- Water solubility: 2.16 g/L
- Vapour pressure: 0.33 Pa (at 20°C) and 0.59 Pa (at 25°C)
- Partition coefficient: 2.69 (HPLC, 2013)
- Storage Conditions: 6 ± 2 °C, protected from light, under nitrogen in the original container
- Stability under test conditions: Not specified, assumed to be stable

Specific details on test material used for the study:

- Purity test date: 30 October 2013
- Storage Conditions: ca. 4 °C in the dark 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 Ltd., Leicestershire, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.24-2.68 kg
- Housing: Animals were individually housed in suspended cages.
- Diet: Food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., 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: 31 March to 14 April 2014

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
- Concentration (if solution): Undiluted

Duration of treatment / exposure:

No washing was done

Observation period (in vivo):

1, 24, 48 and 72 h and 7 days after instillation of test material

Number of animals or in vitro replicates:

3 (1 female and 2 males)

Details on study design:

PRE-TREATMENT:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.

PROCEDURE:
Initially, a single rabbit was treated. A subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Five minutes prior to test item application, a pre-dose anesthesia of ocular anesthetic (two drops of 0.5% tetracaine hydrochloride) was applied to each eye. A volume of 0.1 mL of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released.
Eight hours after test item application, a subcutaneous injection of post-dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 12 h later. No further analgesia was required. After consideration of the ocular responses produced in the first treated animal, two additional animals were similarly treated.

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

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

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

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

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

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

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

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

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

- No initial pain reaction was noted in any animal following instillation of the test item.
- No corneal effects were noted during the study.
- Iridial inflammation was noted in one treated eye one and 24 h after treatment.
- Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in two treated eyes with minimal conjunctival irritation noted in one treated eye at the 24 h observation. Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in one other treated eye at the 48 h observation. Minimal conjunctival irritation was noted in both of these treated eyes at the 72 h observation.
- One treated eye appeared normal at the 48 h observation and two treated eyes appeared normal at the 7-Day observation.

Other effects:

One animal showed a slight body weight loss, although this was considered to be within the normal variation for this species/strain, and two animals showed expected gain in body weight 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	0 / 0 / 1	2 / 2 / 2	1 / 1 / 2	2 / 2 / 2
24 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 1	1 / 2 / 2	0 / 1 / 1	0 / 1 / 1
48 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 1 / 2	0 / 0 / 1	0 / 0 / 1
72 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 1 / 1	0 / 0 / 1	0 / 0 / 0
D 7	- / 0 / 0	- / 0 / 0	- / 0 / 0	- / 0 / 0	- / 0 / 0	- / 0 / 0
Average 24, 48 and 72 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0.3	0.3 / 1.3 / 1.7	0 / 0.3 / 1.0	0 / 0.3 / 0.7
Reversibility	-	-	Completely reversible	Completely reversible	Completely reversible	Completely reversible
Average time (unit) for reversion	-	-	48 h	7 days	7 days	72 h

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test substance is not classified as irritating to eyes according to the Annex VI of 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 item was instilled into the right eye of 3 New Zealand White rabbits (1 female and 2 males). 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 left eye remained untreated and served as control. The eyes were examined and the changes were observed at 1, 24, 48, 72 h and 7 days after treatment and graded according to the Draize method.

No initial pain reaction was noted in any animal following instillation of the test item. No corneal effects were noted during the study. Iridial inflammation was noted in one treated eye one and 24 h after treatment. Moderate conjunctival irritation was noted in all treated eyes one hour after treatment. Moderate conjunctival irritation was noted in two treated eyes with minimal conjunctival irritation noted in one treated eye at the 24 h observation. Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in one other treated eye at the 48 h observation. Minimal conjunctival irritation was noted in both of these treated eyes at the 72 h observation. One treated eye appeared normal at the 48 h observation and two treated eyes appeared normal at the 7-Day observation.

One animal showed a slight body weight loss, although this was considered to be within the normal variation for this species/strain, and two animals showed expected gain in body weight during the study.

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 / 0.3 for iris score; 0.3 / 1.3 / 1.7 for conjunctivae score and 0.0 / 0.3 / 1.0 for chemosis score.

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

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