1,6-Hexanolide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4th November to 2nd December 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Proprietary study conducted according to guidelines and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Hexan-6-olide

EC Number:

207-938-1

EC Name:

Hexan-6-olide

Cas Number:

502-44-3

Molecular formula:

C6H10O2

IUPAC Name:

oxepan-2-one

Constituent 2

Reference substance name:

e-caprolactone

IUPAC Name:

e-caprolactone

Details on test material:

e-Caprolactone, a viscous liquid, supplied by Solvay S.A. Brussels. Batch No: WA2809/0791. Purity: >99%. Prior to dosing, the material was stored in a refrigerator.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

SPF-derived male New Zealad White rabbits (one animal weighed 1.8-2.2kg, three weighed 2.5-3.0kg), obtained from Harlan Olac. Animals underwent an 11 day acclimatisation period. Rabbits were housed individually in stainless steel wire cages without sawdust or woodchips (i.e. no extraneous material that might produce eye irritation). They received 80g food per day (standard laboratory diet), with free access to the food and water. Temperature of the animal room was maintained at 19-22oC, relative humidity 52-72%, artificial light from 7am till 7pm, radio-sound from 7am till 7pm, and approximately 16 air changes per hour.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1ml e-Caprolactone applied to conjunctival sac.

Duration of treatment / exposure:

Substance was applied to conjunctival sac, and eyelid held closed for approximately 1 second.

Observation period (in vivo):

Observations were made at 1, 24, 48, 72 hours and 7 days after treatment.

Number of animals or in vitro replicates:

Initially 4 animals were used, one of these animals was injured and euthanased 1 hour post-treatment. A replacement rabbit was obtained from the supplier.

Details on study design:

Four rabbits were used. 0.1ml test substance was dropped into the conjuctival sac of the left eye. Eye reactions were scored at 1, 24, 48, 72 hours and 7 days after treatment. The scoring system used was that according to Draize (1944), and the results were interpreted according to the Commission Directive 91/325/EEC. The right eye remained untreated to serve as a control.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

mean

Time point:

24/48/72 h

Score:

1.78

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.89

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.44

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.89

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

At 1 hour very slight opacity, iritis, redness and very slight chemosis were observed in three rabbits, and slight iritis, redness and chemosis was observed in the fourth. Severe discharge was observed in animal's 1-3 and moderate discharge in animal 4. The following observations are limited to 3 animals: at 24 hours slight opacity and iritis were observed, slight to moderate redness was observed. Very slight to sight chemosis was observed. At 48 hours opacity was very slight to slight. Redness was slight to moderate. Chemosis was very slight. At 72 hours very slight to slight opacity and slight iritis were observed. Slight to moderate redness were observed. All symptoms had disappeared by day 7.

Other effects:

No additional effects.

Any other information on results incl. tables

Scores for ocular effects

Observation		1h	24h	48h	72h	Mean (24-72h)	7d
Cornea	Opacity	1,1,0	2,2,2	2,2,1	2,2,1	1.78	0,0,0
Iris	Lesion	1,1,1	1,1,1	1,1,1	1,1,0	0.89	0,0,0
Conjunctivae	Erythema	1,1,1	2,2,1	1,2,1	1,2,1	1.44	0,0,0
	Chemosis	1,1,2	2,1,1	1,1,1	0,1,0	0.89	0,0,0

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

According to labelling regulations e-Caprolactone is classified as irritating to the eye.

Executive summary:

The primary irritation of e-Caprolactone to the eye of male rabbits was determined in this guideline study. 0.1ml substance was introduced to the conjunctival sac of the left eye of three rabbits (the right eye remained untreated to serve as a control). The eyes of the rabbits were examined and the ocular reactions graded at intervals up to and including 7 days after treatment. Various signs of irritation were observed (corneal opacity, iris lesion, conjunctival erythema, chemosis and discharge), lthough all symptoms were reversible by Day 7. The substance requires classification as an eye irritant according to Regulation (EC) No 1272/2008 (CLP) and according to Directive 67/548/EEC. It is classified as an eye irritant and assigned the symbol Xi and the risk-phrase R36 "Irritating to eyes". It is an eye irritant category 2 and is assigned the pictogram GHS07 with the signal word "warning" and the hazard statement H319 "causes serious eye irritation".