(Z)-3-hexenyl salicylate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24.09.1984-28.09.1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, equivalent to a valid guidelines and the study was conducted under GLP conditions. The study was performed with test material being used to support the substance on the basis of read-across.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

25485-88-5

Cas Number:

25485-88-5

IUPAC Name:

25485-88-5

Constituent 2

Reference substance name:

Benzoic acid, 2-hydroxy-, cyclohexyl ester

IUPAC Name:

Benzoic acid, 2-hydroxy-, cyclohexyl ester

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): salicylic acid cyclohezyl ester (abbreviated as SCH)
- Molecular formula (if other than submission substance): C13H16O3
- Molecular weight (if other than submission substance): 220.27
- Smiles notation (if other than submission substance): C(=O)(c1c(O)cccc1)OC1CCCCC1
- Physical state: colourless liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach (Germany)
- Weight at study initiation: 2.8-2.9 kg
- Housing: Individually
- Diet: Altromin standard diet 2023 ad libitum
- Water: tap water ad libitum
- Acclimation period: one month

ENVIRONMENTAL CONDITIONS
- Temperature: 20-21 °C
- Humidity: approximately 45-50 %
- Photoperiod: 12 hrs dark / 12 hrs light

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL was instilled into the conjunctival sac of the right eye. The left eye remained untreated as a control.

Observation period (in vivo):

96 hours after exposure

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM:

CORNEA
No ulceration or opacity - 0
Diffuse areas of opacity (except the normal brightness appears slightly cloudy), details of the iris are clearly visible - 1
Easily identifiable translucent area, details of the iris are somewhat shadowed - 2
Nacreous areas, no details of the iris are visible, size of the pupil not identifiable - 3
Opaque cornea, iris not identifiable due to opacity - 4

IRIS
Normal - 0
Markedly opened folds, congestion, enlargement, slight circumcorneal hyperaemia or injection; one of these symptoms or a combination of the various symptoms; the iris still reacts to light (a sluggish reaction is positive) - 1
No reaction to light, haemorrhage, severe damage (one or all of these symptoms) - 2

CONJUNCTIVAE
Redness:
Blood vessels normal - 0
Some blood vessels exhibit a distinct hyperemia (injection) - 1
Diffuse, crimson colour, difficult to identify individual blood vessels - 2
Diffuse, vibrant red - 3

Chemosis:
Eyelids and/or nictitating membrane, no swelling - 0
Each above the normal swelling (including nictitating membrane) - 1
Unambiguous swelling with ectropion of the eyelids - 2
Swelling with approximately half-closed eyelids - 3
Swelling with more than half-closed eyelids - 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

other: Average of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

other: Average of 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 67 + 70 + 72

Time point:

other: Average of 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 68 + 69 + 71

Time point:

other: Average of 24, 48 and 72 hours

Score:

0

Max. score:

3

Reversibility:

fully reversible

Results 5

Irritation parameter:

chemosis score

Basis:

animal: 67 + 68 + 70 + 71 + 72

Time point:

other: Average of 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 6

Irritation parameter:

chemosis score

Basis:

animal: 69

Time point:

other: Average of 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 7

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 72 h

Score:

0.7

Irritant / corrosive response data:

One hour after instillation, all of the animals exhibited minor redness of the conjunctivae and three animals also exhibited minor localised swelling of the conjunctivae in the upper eye area. After 24 hours, three animals exhibited minor redness and five animals exhibited minor swelling. 48 and 72 hours after treatment, all animals were without any symptoms.

This implies an irritation index according to the following formula:

Total reactions after 1, 24, 48 and 72 hours / (Number of animals x number of reading events)

i.e. 17 / (6 x 4) = 0.70

Any other information on results incl. tables

Table 1: Assessment of the reactions of the cornea and iris

Animal number	67		68		69		70		71		72
	Cornea	Iris	Cornea	Iris	Cornea	Iris	Cornea	Iris	Cornea	Iris	Cornea	Iris
1 hour	0	0	0	0	0	0	0	0	0	0	0	0
24 hours	0	0	0	0	0	0	0	0	0	0	0	0
48 hours	0	0	0	0	0	0	0	0	0	0	0	0
72 hours	0	0	0	0	0	0	0	0	0	0	0	0

Table 2: Assessment of the conjunctival reactions

Animal number	67		68		69		70		71		72
	A	B	A	B	A	B	A	B	A	B	A	B
1 hour	1	1	1	0	1	0	1	1	1	1	1	0
24 hours	1	1	0	1	0	0	1	1	0	1	1	1
48 hours	0	0	0	0	0	0	0	0	0	0	0	0
72 hours	0	0	0	0	0	0	0	0	0	0	0	0

A = Redness

B = Chemosis

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the test, a single application of the test material is tolerated by the mucous membrances of the rabbit eye with minor, rapidly reversible reactions of the conjunctivae.

Executive summary:

The eye irritation of the test material was determined under GLP conditions performed in line with the standardised guideline EU Method B5. During the study 6 rabbits were instilled with 0.1 mL of the test material into to the conjunctival sac of the right eye of each animal. Animals were were observed for a period of 96 hours with observations made at 1, 24, 48, 72 and 96 hours after application. The test material was tolerated by the mucous membranes of the eye with minor, rapidly reversible reactions of the conjuctivae.

The test material is considered sufficiently similar to (z)-3-hexenyl salicylate on the basis of read-across such that the results from this study can be used to address the eye irritation potential of (z)-3-hexenyl salicylate.