2-ethoxy-1,3-dimethylcyclohexane

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

This study was conducted between 16 June 2016 and 30 June 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

28 July 2015

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

EC No. 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

1

Reference substance name:

2-ethoxy-1,3-dimethylcyclohexane

EC Number:

944-610-3

Cas Number:

286472-48-8

Molecular formula:

C10H20O

IUPAC Name:

2-ethoxy-1,3-dimethylcyclohexane

Test material form:

liquid

Details on test material:

- Substance name as cited in test report: FRET 05-0293
- Phystical state: clear, colorless liquid
- Storage conditions: ambient temperature (15-25 °C), protected from light

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

Hsdlf:NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Leicestershire, UK
- Age at study initiation: 12 - 52 weeks
- Weight at study initiation: 3.21 - 3.62 kg
- Housing: individually housed in suspended cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23”C
- Humidity (%): 30 - 70%
- Air changes (per hr): >15
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: 16 JUne 2016 To: 30 June 2016

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL test substance as supplied

Duration of treatment / exposure:

4 hours

Observation period:

14 Days

Number of animals:

2

Details on study design:

Study Design
On the day before the test each of a group of two rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to eschar
formation preventing grading of erythema 4

Edema Formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1 millimeter) 3
Severe edema (raised more than 1 millimeter and
extending beyond the area of exposure) 4

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

7 d

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

7 d

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

7 d

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

7 d

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible

Results 5

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal: 1 and 2

Time point:

other: 24 and 72 hours

Score:

ca. 4

Max. score:

4

Reversibility:

fully reversible

Other effects:

Skin Reactions
The individual scores for erythema/eschar and edema are given in Table 1.
Well-defined erythema and slight edema were noted at one treated skin site with very slight erythema and slight edema noted at the other treated skin site immediately and 1 hour after patch removal. Well-defined erythema and slight edema were noted at both treated skin sites at the 24, 48, 72-Hour and 7 Day observations.
Loss of skin elasticity was noted at both treated skin sites at the 72 Hour observation and crust formation was noted at both treated skin sites at the 7 Day observation. Slight desquamation was noted at both treated skin sites at the 14 Day observation.
No corrosive effects were noted.

Body Weight
Both animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Table: Individual Skin Reactions

Skin Reaction	Observation Time (following patch removal)	Individual Scores		Total
		75475 Male	75478 Male
Erythema/Eschar Formation	Immediately	2	1	(3)
	1 Hour	2	1	(3)
	24 Hours	2	2	4
	48 Hours	2	2	(4)
	72 Hours	2Le	2Le	4
	7 Days	2Cf	2Cf	(4)
	14 Days	0D	0D	(0)
Edema Formation	Immediately	2	2	(4)
	1 Hour	2	2	(4)
	24 Hours	2	2	4
	48 Hours	2	2	(4)
	72 Hours	2	2	4
	7 Days	2	2	(4)
	14 Days	0	0	(0)
Sum of 24 and 72 Hour Readings (S)  :       16
Primary Irritation Index (S/4)              :       16/4 = 4.0
Classification                            :       MODERATE IRRITANT

Applicant's summary and conclusion

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

The test item produced a primary irritation index of 4.0 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.
The test item meets the criteria for classification as a Mild irritant (Category 3) according to the Globally Harmonized System of Classification and Labelling of Chemicals.
The test item does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit.

Results

A single 4 Hour, semi occluded application of the test item to the intact skin of two rabbits produced well-defined erythema and slight edema.  Other skin reactions noted were loss of skin elasticity, crust formation and slight desquamation.  No corrosive effects were noted.

Conclusion

The test item produced a primary irritation index of 4.0 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.  

The test item meets the criteria for classification as a Mild irritant (Category 3) according to the Globally Harmonized System of Classification and Labelling of Chemicals.

The test item does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures