Lorenox™

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 February to 17 March 2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP study conducted according to OECD 404 Guideline without any deviation. The substance is adequately identified, but some data on composition is missing. Therefore validation applies with restrictions.

Justification for type of information:

An in vivo study was performed for worldwide (Asia) notification purposes.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24 April 2002.

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2008-04-14&15 /Signed on 2008-07-16.

Test material

Test material information

Constituent 1

Reference substance name:

1,5-Cyclododecadiene, 9-methoxy-1,6,10-trimethyl-

Cas Number:

900779-74-0

Molecular formula:

C16 H28 O

IUPAC Name:

1,5-Cyclododecadiene, 9-methoxy-1,6,10-trimethyl-

Constituent 2

Reference substance name:

1,5-Cyclododecadiene, 10-methoxy-1,5,9-trimethyl-

Cas Number:

900779-83-1

Molecular formula:

C16 H28 O

IUPAC Name:

1,5-Cyclododecadiene, 10-methoxy-1,5,9-trimethyl-

Constituent 3

Reference substance name:

1,5-Cyclododecadiene, 9-methoxy-2,5,10-trimethyl-

Cas Number:

900779-84-2

Molecular formula:

C16 H28 O

IUPAC Name:

1,5-Cyclododecadiene, 9-methoxy-2,5,10-trimethyl-

Constituent 4

Reference substance name:

1,5-Cyclododecadiene, 9-methoxy-1,5,10-trimethyl-

Cas Number:

900779-85-3

Molecular formula:

C16 H28 O

IUPAC Name:

1,5-Cyclododecadiene, 9-methoxy-1,5,10-trimethyl-

Test material form:

liquid

Details on test material:

- Storage condition of test material: Room temperature

Specific details on test material used for the study:

- Date received: 10 February 2009 (Flask 1); 18 February 2009 (Flask 2)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste – F40260 Linxe)
- Age at study initiation: 12-13 weeks
- Weight at study initiation: 2.64-3.33 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: Foodstuff (SDS –C15), ad libitum
- Water: Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-24 °C
- Humidity: 48-64 %
- Air changes: ca. 15 changes per hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 24 February to 17 March 2009

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

Skin reactions were appreciated 1, 24, 48 and 72 hours, Day 4 to 14 after removal of the patch.

Number of animals:

3 females

Details on study design:

PRETEST
Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated during 4 hours.

TEST SITE
- Area of exposure: Approximately 24 h before the test, the rabbit’s back and flanks were shorn using electric clippers equipped with a fine comb, so as to expose an area of skin about 6 cm^2 per patch.
- As no tissue destruction was noted after a treatment during 3 minutes and 1 hour, the test item was applied, as supplied, at a dose of 0.5 mL, on an undamaged skin area of one flank of each animal, during 4 hours.
- Type of wrap if used: The patch was secured in position with a strip of surgical adhesive tape under semiocclusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the removal of the patch, the treated area was rinsed with distilled water.
- Time after start of exposure: 4 h

SCORING SYSTEM: According to OECD guideline 404

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

probability of mild irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 5 days

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

- A well defined erythema was noted on the treated area of all animals, 24 hours after the patch removal. This erythematous reaction was totally reversible between day 3 and day 7.
- A very slight to moderate oedema was noted on the treated area of all animals, 24 hours after the patch removal. This oedematous reaction was totally reversible between day 2 and day 6.
- Regarding the cutaneous structure, a slight dryness was noted in all animals from day 2, day 3 or day 5. This cutaneous reaction was totally reversible on day 9 in one animal but slight dryness was registered until the last day of the test (day 14) in the two others.

Other effects:

None

Any other information on results incl. tables

Table 7.3.1/1: Individual and mean skin reactions following 4 hour exposure

Skin reaction	Observation time (following patch removal)	Individual Scores – Rabbit Number and Sex
		A9499Female	A9523Female	A9524Female
Erythema/Eschar formation	1 h	2	1	2
	24 h	2	2	2
	48 h	1	2	2
	72 h	0	2	2
	Day 4	-	2	2
	Day 5	-	1	1
	Day 6	-	1	0
	Day 7	-	0	-
	Total (24, 48 and 72 hours)	3	6	6
	Mean (24, 48 and 72 hours)	1.0	2.0	2.0
Oedema formation	1 h	2	2	1
	24 h	1	3	2
	48 h	0	2	1
	72 h	0	2	1
	Day 4	-	1	1
	Day 5	-	1	0
	Day 6	-	0	0
	Day 7	-	0	-
	Total (24, 48 and 72 hours)	1	7	4
	Mean (24, 48 and 72 hours)	0.3	2.3	1.3

 

Note:

A9499: slight dryness at D2, D3, D6, D7 & D8

A9523: slight dryness at D3, D4, D9, D10, D13 & D14; dryness between D5 and D8

A9524: slight dryness at D5, D8, D9, D10, D13 & D14; dryness at D6 & D7

Applicant's summary and conclusion

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

Under the test conditions, test item is not classified according to CLP Regulation (EC) No. 1272/2008 but is classified as "Category 3 (mild irritant)" based on Globally Harmonized System (GHS).

Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted test item was applied on the shorn skin of the flanks of 3 female New Zealand White rabbits. On the opposite flank an untreated area was served as the control. Test sites were covered with a semi-occlusive dressing for 4 h. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hours, Day 4 to 14 after removal of the patch. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated during 4 hours.

 

A well defined erythema was noted on the treated area of all animals, 24 hours after the patch removal. This erythematous reaction was totally reversible between day 3 and day 7. A very slight to moderate oedema was noted on the treated area of all animals, 24 hours after the patch removal. This oedematous reaction was totally reversible between day 2 and day 6. Regarding the cutaneous structure, a slight dryness was noted in all animals from day 2, day 3 or day 5. This cutaneous reaction was totally reversible on day 9 in one animal but slight dryness was registered until the last day of the test (day 14) in the two others.

 

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 1.0 / 2.0 / 2.0 for erythema and 0.3 / 2.3 / 1.3 for oedema.

 

Under the test conditions, test item is not classified according to CLP Regulation (EC) No. 1272/2008 but is classified as "Category 3 (mild irritant)" based on Globally Harmonized System (GHS).

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.