1-Ethoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl)-benzene

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Mar 12 - Apr 09, 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

July 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1-ethoxy-2,3-difluoro-4-[(1s,4r)-4-propylcyclohexyl]benzene

EC Number:

605-718-3

Cas Number:

174350-05-1

Molecular formula:

C17H24F2O

IUPAC Name:

1-ethoxy-2,3-difluoro-4-[(1s,4r)-4-propylcyclohexyl]benzene

Test material form:

solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Strain: Albino rabbit, Crl:KBL(NZW)
Source: Charles River Wiga GmbH, Kifßlegg
Age: about 27 weeks
Initial Weight: 3.66 kg (3.15-4.25 kg)

Identification and adaptation
The animal was kept in the experimental room for more than 7 days to allow them to acclimatize. The animal was uniquely identified by a tattoo in the ear displaying the animal number. An individual cage card was affixed to the cage displaying the study number, test material, day of treatment, and animal number.
Housing and diet
The rabbits were housed in an air-conditioned room of about 28 m^2 in the Institute of Toxicology. Lighting was controlled by a timer to provide a 12-hour light and a 12-hour dark regime. They were kept separately in special rabbit cages (manufacturer: Becker; type K99/30 KU, floor area about 5400 cm^2, a shelter with an integrated sitting board of about 1820 cm^2; overall height: 60 cm) with plastic grids placed on mobile racks. The collection pans underneath the cages were cleaned at least three times a week. The cages were cleaned before the start of the study. Temperature and relative humidity were measured using a thermohygrograph. The room temperature varied from 20 to 21 °C and the relative humidity from 59 to 68 %. The rabbits received a commercial diet for rabbits, Altromin Standard Diet ad libitum and fresh tap water from Makrolon drinking bottles ad libitum. According to the specifications given by the manufacturer, the diet had been checked by independent laboratories. Analysis included both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics. The drinking water was periodically analyzed according to the German regulations for human drinking water.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: aqua pro injectione

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hours after removal of patches and then daily up to day 8

Number of animals:

3 females

Details on study design:

Observations for clinical symptoms
The rabbit was examined for skin alterations, behavior, and general condition 1 hour after removal of the patch, after 24, 48, 72 hours, and then daily up to experimental day 8.Skin changes at the application sites were evaluated according to the DRAIZE-, OECD-and EEC recommendations.
Grading scale for evaluation:
Erythema and eschar formation
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to eschar formation preventing grading of erythema: 4
Maximum possible: 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 approx. 1 mm): 3
Severe edema (raised more than 1 mm and extending beyond area of exposure): 4
Maximum possible: 4
Total possible irritation score (maximum): 8
Mean score = Mean grading for erythema or edema of all the rabbits per time point
Mean cumulative score = Mean grading of all readings for erythema and edema per time point
Mean score per animal = Mean grading for each animal of erythema or edema (24, 48, and 72 hours after removal of the patches)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Any other information on results incl. tables

0.5 g of the test material was administered. After a single application to the intact dorsal skin of a rabbit, for 4 hours under semiocclusive conditions, no signs of irritation were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is considered to possess no skin irritating properties.

Executive summary:

The purpose of this assay was to identify the skin irritation/corrosion potential of the test material when applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions.

This study should provide a rational basis for risk assessment to the irritating potential of the test item in man and was conducted according to OECD 404.

To test for primary skin irritation, 0.5 g of the test material was mixed with some drops of aqua pro injectione to ensure good contact with the skin. Afterwards the test material was spread onto 6 cm2 patches and applied to the intact skin of three previously shaven rabbits for a 4 hours period under semiocclusive conditions.

The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for another 7 days.

No signs of irritation were observed after administration. Thus, the test item is considered to possess no skin irritating properties.

Day	1(1 hour)	2(24 hours)	3(48 hours)	7(72 hours)
edema	0	0	0	0
erythma	0	0	0	0

 

According to EU Regulation No. 1272/2008 and CLP the test material must not be classified as an irritant to the skin.