4-trans-(4-trans-Propylcyclohexyl)-cyclohexancarbonic acid

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002-01-22 to 2002-02-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

07-1992

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

07-1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

(1r,1's,4r,4'r)-4'-propyl-[1,1'-bi(cyclohexane)]-4-carboxylic acid

EC Number:

613-782-9

Cas Number:

65355-32-0

Molecular formula:

C16 H28 O2

IUPAC Name:

(1r,1's,4r,4'r)-4'-propyl-[1,1'-bi(cyclohexane)]-4-carboxylic acid

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

SPF

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne, France
- Age at study initiation: 12 weeks (males) and 10-11 weeks (females)
- Weight at study initiation: 2.16 - 2.4 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood, and haysticks for gnawing
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Days 1 to 7

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

Before application, the test material was moistened with 0.1 mL of purified water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 500 mg

VEHICLE
Name: purified water

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

2 females and 1 male

Details on study design:

TEST SITE
Four days before treatment, one flank was clipped. The skin of the animals was examined one day before treatment, and regrown fur of all animals was again clipped. Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, 500 mg of the test item was placed on a surgical gauze patch, which was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

OBSERVATION TIME POINTS
1 hour after removal, after 24, 48, 72 hours, and then daily up to experimental day 7.
Viability/Mortality/Clinical signs: Daily from delivery of the animals to the termination of test.
Body weights: At start of acclimatization, on the day of application and at termination of observation.
Necropsy: Not performed as animals were sacrificed at termination of observation.

SCORING SYSTEM: The skin reaction was assessed according to the numerical scoring system
(Erythema: 0= no erythema, 1= very slight erythema, 2= well defined erythema, 3= moderate to severe erythema, 4= severe erythema. Edema: 0= no edema, 1= very slight edema, 2= slight edema, 3= moderate edema, 4= severe erythema) listed in the EU Regulation (EC) No 1272/2008 (CLP), as amended for fifteenth time in Regulation (EU) No 2020/217, approximately 1, 24, 48 and 72 hours, as well as 7 days after the removal of the dressing, gauze patch and test item.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritating potential could be detected.

Other effects:

- pH measurements: Prior to the application, the pH of the test item was determined at a concentration of 1% in water with a pH test strip (E. Merck, D-64271 Darmstadt / Germany). The pH was found to be 5.

- Other adverse local effects: Very slight erythema was observed at the test site of two animals 1 hour after treatment (table 1). The test item did not, however, elicit any signs of irritation at the application site of any animal at the 24-, 48-, 72-hour or 7-day readings. The mean values from 24 to 72 hours were, therefore, 0 for erythema and 0 for edema (table 2).

Any other information on results incl. tables

Table 1: Skin irritation scores – individual values

Animal Number	Sex	Evaluation Interval	Erythema	Edema
55	M	1 hour	1	0
56	F		1	0
57	F		0	0
55	M	24 hours	0	0
56	F		0	0
57	F		0	0
55	M	48 hours	0	0
56	F		0	0
57	F		0	0
55	M	72 hours	0	0
56	F		0	0
57	F		0	0
55	M	7 days	0	0
56	F		0	0
57	F		0	0

M= Male

F=Female

 

Table 2: Skin irritation scores – individual mean values after 24, 48 and 72 hours

Animal Number	Sex	Erythema	n	Edema	n
55	M	0	3	0	3
56	F	0	3	0	3
57	F	0	3	0	3

n= number of available data points

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not induce significant or irreversible damage to the rabbit skin and is considered to be "not irritating" to rabbit skin.

Executive summary:

The primary skin irritation potential of the test item was investigated by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48, 72 as well as 7 days after removal of the dressing. The application of the test item caused very slight erythema at the test site of two animals 1 hour after treatment. The test item did not, however, elicit any signs of irritation at the application site of any animal at the 24-, 48-, 72- hour or 7-day readings. The mean values from 24 to 72 hours were, therefore, 0 for erythema and 0 for edema. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval. Thus, the test item did not induce significant or irreversible damage to the rabbit skin. Based upon the referred classification criteria (EU Regulation (EC) No 1272/2008 (CLP), as amended for fifteenth time in Regulation (EU) No 2020/217), the test item is considered to be "not irritating" to rabbit skin.