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EC number: 265-745-8 | CAS number: 65405-77-8
Endpoint summary
Administrative data
Description of key information
EYE
Key study:non-irritant; rabbit; equivalent to EU Method B5; Potokar (1984b)
Key value for chemical safety assessment
Skin irritation / corrosion
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- 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.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes
- 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 - 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 - 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
- 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
- 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
- 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
- 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
- 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
- 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 - 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.
- Endpoint:
- eye irritation: in vivo
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- 1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Please see 'Justification for read-across to support the REACH registration of (z)-3-hexenyl salicylate' document attached (section 13) for full details.
It is proposed to read-across to another salicylate substance in order to fulfil data requirements.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please see ''Justification for read-across to support the REACH registration of (z)-3-hexenyl salicylate' document attached for full details.
Source substance: cyclohexyl salicylate (EC 400-410-3, CAS 25485 88-5).
Target substance: (z)-3-hexenyl salicylate (EC 265-745-8, CAS 65405-77-8)
3. ANALOGUE APPROACH JUSTIFICATION
Please see 'Justification for read-across to support the REACH registration of (z)-3-hexenyl salicylate' document attached for full details.
(z)-3-hexenyl salicylate (the target substance) and the read-across substance cyclohexyl salicylate (source substance) have been characterised using the categories and databases present in the OECD QSAR Toolbox. From the profiling, it can be seen that the two substances share structural similarities and also ‘mechanistic action’ similarities which are both general and endpoint specific. The main difference observed is structural. The target substance ((z)-3-hexenyl salicylate) contains an acyclic hexenyl chain and the source substance (cyclohexyl salicylate) contains a cyclic hexyl group.
The output from the OECD QSAR Toolbox shows that the profiles of (z)-3-hexenyl salicylate and cyclohexyl salicylate are sufficiently similar such that any available data from the source substance can be used to address the following endpoints in the REACH registration dossier for (z)-3-hexenyl salicylate:
4. DATA MATRIX
Please see 'Justification for read-across to support the REACH registration of (z)-3-hexenyl salicylate' document attached for full details. - Reason / purpose for cross-reference:
- read-across source
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Remarks:
- all animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Irritation parameter:
- iris score
- Basis:
- mean
- Remarks:
- all animals
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- fully reversible
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal: 67 + 70 + 72
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 3
- Reversibility:
- fully reversible within: 48 hours
- Irritation parameter:
- conjunctivae score
- Remarks:
- Redness
- Basis:
- animal: 68 + 69 + 71
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 3
- Reversibility:
- fully reversible
- Irritation parameter:
- chemosis score
- Basis:
- animal: 67 + 68 + 70 + 71 + 72
- Time point:
- 24/48/72 h
- Score:
- 0.33
- Max. score:
- 4
- Reversibility:
- fully reversible within: 48 hours
- Irritation parameter:
- chemosis score
- Basis:
- animal: 69
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- 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.
- 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.
Referenceopen allclose all
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
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Eye irritation
The eye irritation of the test material was determined under GLP conditions using a method equivalent to the standardised guideline EU Method B5. During the study 6 rabbits were with 0.1 mL of the test material added to the conjunctival sac of the right eye of each animal. Animals 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 (z)-3-hexenyl salicylate.
Skin irritation
A waiver was submitted to address the skin irritation/corrosion data requirement. The endpoint was considered suitably addressed with the use of alternative data, the conclusions of which were considered suitable for classification and labelling and risk assessment purposes.
Justification for classification or non-classification
According to Regulation EC 1272/2008, the substance does not meet the classification criteria for skin or eye irritation.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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