2-Oxetanone, 3-C12-16-alkyl-4-C13-17-alkylidene derivs., (4E)-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

8 September 1998 - 12 September 1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed according to international guidelines and under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-Oxetanone, 3-C12-16-alkyl-4-C13-17-alkylidene derivs.

EC Number:

284-932-5

EC Name:

2-Oxetanone, 3-C12-16-alkyl-4-C13-17-alkylidene derivs.

Cas Number:

84989-41-3

Molecular formula:

C28.H52.O2 - C36.H68.O2

IUPAC Name:

(4E)-4-(C13-C17)alkylidene-3-(C12-C16)alkyloxetan-2-one

Details on test material:

Identity: P-2290
Chemical name: 2-Oxetanone, 3-C12-16-alkyI-4-C13-17-alkylidene derivatives
Appearance: Brown waxy liquid
Storage conditions: 4°C in the dark
Batch number: No data
Composition: Alkyl ketene dimer > 85%, Toluene <20ppm
Sample receive: 8 May 1998

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England.
- Age at study initiation: 16 weeks
- Weight at study initiation: 3.0-3.4 kg
- Housing: They were housed individually in metal cages with perforated floors in Building R14 Room 4
- Diet (e.g. ad libitum): ad libitum, standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellet)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 34 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5-20
- Humidity (%): 43-66
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 8 September 1998 - 12 September 1998

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as the control

Amount / concentration applied:

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

Duration of treatment / exposure:

One single exposure

Observation period (in vivo):

Until 3 days after instillation

Number of animals or in vitro replicates:

3

Details on study design:

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

SCORING SYSTEM:
Cornea opacity: degree of density (area most dense taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent areas, details of iris slightly obscured
3 Nacreous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

Area of cornea involved:
0 None
1 One quarter (or less) but not zero
2 Greater than one quarter, but less than half
3 Greater than half, but less than three quarters
4 Greater than three quarters, up to whole area

Iris:
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae Redness: (refers to the most severe reading of palpebral and bulbar conjunctivae, as compared to the control eye)
0 Blood vessels normal
1 Some blood vessels definitely hyperaemic (injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffise beefy red

Chemosis: (lids and/or nictating membranes)
0 No swelling
1 Any swelling above normal (includes nictating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half-closed
4 Swelling with lids more than half-closed

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72 hours

Score:

0

Max. score:

2

Remarks on result:

other: No effects observed

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72 hours

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72 hours

Score:

0

Max. score:

4

Remarks on result:

other: No effects observed

Irritant / corrosive response data:

No corneal damage or iridial inflammation was observed. A diffuse, crimson colouration of the conjunctivae was seen in one animal. Transient hyperaemia of the blood vessels was seen in the remaining two animals. These reactions had resolved by one or two days after instillation.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

Anim. No.	Effect	Days after application				Mean score cornea Days 1/2/3	Mean score iritis Days 1/2/3	Mean score redness Days 1/2/3	Mean score chemosis Days 1/2/3	Mean score discharge  Days 1/2/3
		1 (hour)	1	2	3
1123*	Cornea-opacity Cornea-area Iris Redness Chemosis Discharge	0 0 0 2 0 -	0 0 0 1 0 -	0 0 0 0 0 -	0 0 0 0 0 -	0	0	0.33	0	-
1188	Cornea-opacity Cornea-area Iris Redness Chemosis Discharge	0 0 0 1 0 -	0 0 0 1 0 -	0 0 0 0 0 -	0 0 0 0 0 -	0	0	0.33	0	-
1189	Cornea-opacity Cornea-area Iris Redness Chemosis Discharge	0 0 0 1 0 -	0 0 0 0 0 -	0 0 0 0 0 -	0 0 0 0 0 -	0	0	0	0	-
Mean all anim.						0	0	0.22	0	-

- No scoring performed

* pilot animal

Applicant's summary and conclusion

Conclusions:

Based on the scores for this study the test substance is not classified for eye irritation according to OECD GHS criteria.

Executive summary:

A study was performed to assess the eye irritation potential of P-2290 to the rabbit. The method followed was that described in the following guidelines: EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (Official Journal No. L383Ay 29.12.92), Part B, Method B.5. Acute toxicity (eye irritation). OECD Guideline for the Testing of Chemicals No. 405, "Acute Eye lrritation/Corrosion", Adopted 24 February 1987.

Thee rabbits were each administered a single ocular dose of a volume of 0.1 ml of the test substance, and observed for three days after instillation.

A single instillation of P-2290 into the eye of the rabbit elicited transient very slight to well-defined conjunctival irritation only. All reactions had resolved by two days after instillation. Based on the scores for this study the test substance is not classified for eye irritation according to OECD GHS criteria.