Cyclopropanecarboxylic acid, (3Z)-3-hexen-1-yl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 27 October 1997 and 01 November 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to OECD/EU guideline under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The values for temperature and humidity were recorded as 13 - 25.5°C and 25 - 73% respectively. These were outside the ranges as stated in the protocol. These deviations are not considered to affect the validity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

The values for temperature and humidity were recorded as 13 - 25.5°C and 25 - 73% respectively. These were outside the ranges as stated in the protocol. These deviations are not considered to affect the validity of the study.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Montaverdi

IUPAC Name:

Montaverdi

Test material form:

other: colourless liquid

Details on test material:

Identity: 97-204-01
Commercial name: Montaverdi
Appearance: Clear colourless liquid
Storage conditions: Room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animals for this study were selected from a stock supply of healthy adult rabbits of the New Zealand White strain, obtained from Charles River UK Ltd., Margate, Kent, England.
The animals were in the weight range of 3.0 to 3.5 kg and approximately 13 to 15 weeks of age, prior to treatment (Day 1). All rabbits were acclimatised to the experimental environment.
The rabbits were selected without conscious bias for the study. They were housed individually in metal cages with perforated floors in Building R14 Room 5.
A standard laboratory diet SDS Stanrab (P) SQC Rabbit Diet and drinking water were provided ad libitum
The batch of diet used for the study was analysed for nutrients, contaminants or micro-organisms.
Results of routine physical and chemical examination of drinking water as conducted by the supplier, are made available to Huntingdon Life Sciences Ltd as quarterly summaries.
Animal room temperature was maintained at l3 to 25.5°C and relative humidity at 25 - 73%. These environmental parameters were recorded daily. Air exchange was maintained at approximately 19 air changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.
Each animal was identified by a numbered aluminium tag placed through the edge of one ear. This number was unique within the Huntingdon Life Sciences Acute Toxicology Department throughout the duration of the study. Each cage, was identified by a coloured label displaying the study schedule number, animal number and initials of the Study Director and Home Office licensee.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The contralateral eye remained untreated.

Amount / concentration applied:

0.1 ml of the test substance

Duration of treatment / exposure:

Up to 1 hour

Observation period (in vivo):

Examination of the eyes was made after 1 hour and 1, 2, 3 days (equivalent to 24, 48 and 72 hours) after instillation.

Number of animals or in vitro replicates:

3 animals were tested in total. One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed.

Details on study design:

TREATMENT PROCEDURE
The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial or conjunctival inflammation.
One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed (pilot animal).
A volume of 0.1 ml of the test substance was placed into the lower everted lid of one eye of each animal.
The eyelid was then gently held together for one second before releasing. The contralateral eye remained untreated.

OBSERVATIONS
Clinical signs
All animals were observed daily for signs of ill health or toxicity.
Ocular responses
Examination of the eyes was made after 1 hour and 1, 2, 3 days (equivalent to 24, 48 and 72 hours) after instillation. Observation of the eyes was aided by the use of a handheld light.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal: 2452 Female

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal: 2453 Female

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal: 2454 Female

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal: 2452 Female

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: No effects observed

Results 5

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal: 2453 Female

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: No effects observed

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal: 2454 Female

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

other: No effects observed

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal: 2452 Female

Time point:

other: 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Results 8

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal: 2453 Female

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 9

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal: 2454 Female

Time point:

other: 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 10

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal: 2452 Female

Time point:

other: 24, 48 and 72

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Results 11

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal: 2453 Female

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal: 2454 Female

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

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 two rabbits accompanied by slight swelling of the eyelids. Transient hyperaemia of blood vessels of the conjunctivae was seen in the remaining animal.
All reactions had resolved completely by two or three 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

Table 1                       Ocular Reactions

 

Rabbit no. and sex	Region of eye		One hour	Day after instillation
				1	2	3
2452 Female*	Cornea	Density	0	0	0	0
		Area	0	0	0	0
	Iris		0	0	0	0
	Conjunctiva	Redness	1	1	0	0
		Chemosis	0	0	0	0
2453 Female	Cornea	Density	0	0	0	0
		Area	0	0	0	0
	Iris		0	0	0	0
	Conjunctiva	Redness	2	2	1	0
		Chemosis	1	0	0	0
2454 Female	Cornea	Density	0	0	0	0
		Area	0	0	0	0
	Iris		0	0	0	0
	Conjunctiva	Redness	2	1	0	0
		Chemosis	1	0	0	0

 

* - Pilot animal

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Instillation of 97-204-01 into the rabbit eye elicited transient very slight to well-defined conjunctival irritation but not sufficient to warrant classification.

Executive summary:

An in vivo study was performed to assess the eye irritation potential of Montaverdi to the rabbit. The method followed was that described in:

EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (01 No. L383A, 29.12.92), Part B, Method B.5. Acute toxicity (eye irritation) or OECD Guideline for Testing of Chemicals No. 405, "Acute Eye Irritation/Corrosion". Adopted: 24 February 1987. Three 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 Montaverdi into the eye of the rabbit elicited transient very slight to well-defined conjunctival irritation. The scores obtained however do not lead to classification according to the criteria set out in the DSD 67/548/EC or the CLP Regulation (EC) 1272/2008.