Cineole

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:

Between 02 April 1991 and 15 April 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

To address toxicological endpoints as part of the REACH registration of Cineole (Target Substance) it is proposed to read-across to Clarycet (Source Substance). The use of read-across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible. The Target Substance and Source Substance have been characterised in using the categories and databases present in the OECD (Q)SAR Toolbox. From the profile, it can be seen that the two substances share structural similarities and also "mechanistic action" similarities which are both general and endpoint specific. Therefore read-across is justified.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Clarycet

IUPAC Name:

Clarycet

Constituent 2

Reference substance name:

131766-73-9

EC Number:

603-508-6

Cas Number:

131766-73-9

IUPAC Name:

131766-73-9

Constituent 3

Reference substance name:

Tetrahydro-4-methyl-2-propyl-2H-pyran-4-yl acetate

IUPAC Name:

Tetrahydro-4-methyl-2-propyl-2H-pyran-4-yl acetate

Details on test material:

- Name of test material (as cited in study report): Clarycet (2H-Pyran-4-ol, tetrahydro-4-methyl-2-propyl: acetate).
- Molecular weight (if other than submission substance): 200.28
- Smiles notation (if other than submission substance): C1(C)(OC(C)=O)CC(CCC)OCC1
- Structural formula attached as image file (if other than submission substance): see Fig.
- Physical state: Clear colourless liquid
- Analytical purity: > 94 %
- Lot/batch No.: 6370
- Storage condition of test material: Room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: froxfield Farms (UK) Ltd, Petersfield, Hampshire, England.
- Age at study initiation: 14 - 16 weeks
- Weight at study initiation: 3.6 to 4.4 kg
- Housing: Individually in metal cages with perforated floors.
- Diet (e.g. ad libitum): SDS Stanrab (P) diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Acclimated for unspecified time period.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean maximum: 8.2 °C; mean minimum: 18.1 °C
- Humidity (%): 50.5 %
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The contralateral eye remained untreated in each rabbit.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution):

Duration of treatment / exposure:

The test substance was not removed from the eye by washing.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

Three

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not done.
- Time after start of exposure: Not applicable.

SCORING SYSTEM: See other information on materials and methods.

TOOL USED TO ASSESS SCORE: None specified

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 1 hour

Score:

3.3

Max. score:

13

Reversibility:

fully reversible within: 7 Days

Results 2

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: Day 1

Score:

5

Max. score:

13

Reversibility:

not fully reversible within: 7 days

Results 3

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: Day 7

Score:

0

Max. score:

13

Reversibility:

fully reversible

Any other information on results incl. tables

Corneal opactities had developed one or 24 hours (1 day) after instillation in all three animals. The responses persisted up to three days before resolving.

A diffuse crimson-red colouration of the conjunctivae in all three animals. This was accompanied in one animal by obvious swelling with partial everson of the eyelid.

All reactions had resolved four or seven days after instillation.

Ocular reactions elicited by the test substance:

Rabbit No. and Sex	Region of the eye		One hour	Days after instillation
				1	2	3	4	7
587 F	Cornea		0	2	1	0	0	0
	Iris		0	0	0	0	0	0
	Conjunctiva	Redness	2	2	2	1	1	0
		Chemosis	2	2	1	1	0	0
588 F	Cornea		0	1	1	1	1	0
	Iris		0	0	0	0	0	0
	Conjunctiva	Redness	2	2	2	2	2	0
		Chemosis	1		1	1	1	0
629 F	Cornea		1	2	1	0	0	0
	Iris		0	0	0	0	0	0
	Conjunctiva	Redness	1	2	2	1	0	0
		Chemosis	1	1	1	0	0	0

To address toxicological endpoints as part of the REACH registration of Cineole (Target Substance) it is proposed to read-across to Clarycet (Source Substance).

 

The use of read-across works within the spirit of REACH and the stated aim of the legislation to reduce animal testing where possible.

 

The Target Substance and Source Substance have been characterised in using the categories and databases present in the OECD (Q)SAR Toolbox. From the profile, it can be seen that the two substances share structural similarities and also "mechanistic action" similarities which are both general and endpoint specific.

Therefore read-across is justified.

See Section 13 document, Read Across Justification_Clarycet

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The results of an in vivo eye irritation study on the structural analogue, Clarycet, are provided as part of a weight of evidence. The test substance was assessed for eye irritation according to OECD 405. Instillation of the test substance into the rabbit eye elicited transient corneal opacification and slight conjunctival irritation. The test substance does not require labelling with the risk phrase R36 "irritating to eyes", as described in the EEC Directives 83/467/EEC and 86/43/EEC, Annex VI Part II(D).