4-trans-Methoxy-4-trans-propyl-[1,1-bicyclohexyl]

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Jan 10 - May 24, 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(1r,1's,4r,4'r)-4-methoxy-4'-propyl-1,1'-bi(cyclohexane)

EC Number:

619-269-6

Cas Number:

97398-80-6

Molecular formula:

C₁₆H₃₀O

IUPAC Name:

(1r,1's,4r,4'r)-4-methoxy-4'-propyl-1,1'-bi(cyclohexane)

Test material form:

liquid: viscous

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

CRL:KBL(NZW)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River WIGA GmbH, Kisslegg
- Age at study initiation: 27 weeks
- Weight at study initiation: 3.95 kg
- Housing: kept serarately in a special rabbit cage (manufacturer: Becker; type K99/30 KU) on a mobile rack
- Diet: ad libitum, commercial diet for rabbits, Provimi Kliba 3418.0 and ssniff K snack
- Water: ad libitum, fresh community tap water from Makrolon drinking bottles
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 to 27
- Humidity (%): 23 to 98
The room temperature and relative atmospheric humidity in the animal room was transiently outside the target range of 16 to 22 °C and > 40 %. These deviations did not affect the integrity or outcome of the study.
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hours after removal of patches and then daily up to day 22

Number of animals:

1f

Details on study design:

TEST SITE
- Area of exposure: 0.5 mL of the test material was spread onto a patch of about 6 cm2.
- Type of wrap: The patch was fastened to the left side of the animal’s back and kept in place by a self-adhesive fabric (Fixomull®stretch, Beiersdorf).

REMOVAL OF TEST SUBSTANCE
- Washing: no, residues were wiped off
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
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 22.

SCORING SYSTEM:
- Method of calculation: Skin changes at the application site was evaluated according to the DRAIZE-, OECD- and EEC recommendations.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 22 days

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritant / corrosive response data:

After a single application to the intact dorsal skin of a rabbit, for 4 hours under semiocclusive conditions, erythema (scores 2 to 4) from day 1 up to the end of the study and edema (scores 1 to 3) from day 1 up to day 7 of the study occurred. Furthermore, small scales from day 13 up to the end of the study and epithelization from day 15 up to the end of the study were observed. Brittle skin from day 8 up to day 14 was seen at the site of application.

Other effects:

- Other adverse systemic effects: No signs of clinical toxicity were detected. The animal survived the observation period. Body weight development of the treated rabbit was inconspicuous.

Any other information on results incl. tables

Pretests:

Prior to testing the pH of the preparation was determined with pH-test strips. The pH was found to be about 5.

The test material was screened for its irritating potential using the hen's egg test on the chorioallantoic membrane (HET-CAM) as described below. Fertile hen eggs, on day 10 of incubation, provided the test system. The eggshell was entered above the air cell by a dentist's rotary and then pared off. The shell with the attached outer membrane and inner egg membrane was carefully opened. After the membrane had been moistened with isotonic sodium chloride solution, it was removed to expose the chorioallantoic membrane (CAM) of the fertilized egg, which lies immediately below. The CAM of fertilized and incubated hen eggs provides a suitable model for membranes with an intact and functional vascular system. The CAM has no nerve fibers in the early stages of development and is, thus, regarded as being insensitive to pain. In this model the cumulative irritation score of the test item was 0.00.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test material caused irritative skin effects.

Executive summary:

The liquid test material was spread onto patches and applied to the intact skin of a previously shaven rabbit for 4 hours under semi-occlusive conditions. The study was performed initially with one animal, which showed signs of irritation (erythema, edema,  brittle skin, and small  scales) and therefore no more animals were treated. The first examination of the treated skin followed 1 hour after patch removal. Thereafter, examinations were performed daily for a further 21 days. No signs of pain were observed after administration of the test material. Under the conditions of the present study erythema (scores 2 to 4) from day 1 up to the end of the study and edema (scores 1 to 3) from day 1 up to day 7 of the study occurred. Furthermore, small scales were observed from day 13 up to the end of the study and epithelization from day 15 up to the end of the study. Brittle skin from day 8 up to day 14 was seen at the site of application. The test material caused irritative skin effects.