Cineole

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

Between 25th March and 8th 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:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

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: Liquid
- Analytical purity: >94 %
- Impurities (identity and conce
- Lot/batch No.: 6370
- Storage condition of test material: Room temperature in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd., Margate, Kent, England.
- Age at study initiation: 7 - 10 weeks
- Weight at study initiation: 216 - 244 g
- Fasting period before study:
- Housing: Individually in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): Standard laboratory rodent diet ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum period of 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Daily mean minimum and maximum temperatures were 21 - 23 °C
- Humidity (%): 54 % RH
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 50 mm x 50 mm
- % coverage: 10 %
- Type of wrap if used: Gauze held in place with an impenetrable dressing encircled firmly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin was decontaminated usign warm water 30 - 40 °C and blotting dry with absorbent paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.04 mL/kg body weight (specific gravity 0.98).
- Concentration (if solution): 2 g/kg bw


VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable

Duration of exposure:

24 h

Doses:

2 g/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of 5 hours). On subsequent days the animals were observed once in the morning and again at the end of the experimental day.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, including the nature, severity, approximate time of onset and duration of each sign. Individual body weight of rats on Days 1 (day of dosing), 8 and 15.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 other: g/kg bodyweight

Based on:

test mat.

Remarks on result:

other: There were no deaths following exposure

Mortality:

There were no deaths following a single dermal dose of the test substance at 2 g/kg bodyweight.

Clinical signs:

other: There were no signs of systemic reaction. Sites of application of the test substance showed no irritation or other dermal changes (scores of zero of erythema and oedema were recorded for all animals).

Gross pathology:

Terminal autopsy revealed no macroscopic abnirmalities.

Any other information on results incl. tables

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

Conclusions:

The results of an acute dermal toxicity study on the structural analogue, Clarycet, are provided as part of a weight of evidence. The acute lethal dermal dose to rats of the test substance was found to be > 2.0 g/kg bodyweight.

Executive summary:

An acute dermal toxicity study was performed according to OECD Guideline for Testing of Chemicals 402 "Acute Dermal Toxicity", and EEC Methods for the determination of toxcity, Directives 84/449/EEC (OJ No. L251, 19.9.84), Part B, Method B3. Acute Toxicity (Dermal).

The acute lethal dermal dose to rats of the test substance was found to be > 2.0 g/kg bodyweight.