Reaction mass of stereoisomers of 4-METHYLENE-2-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-TETRAHYDRO-PYRAN and; 4-METHYL-6-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-3,6-DIHYDRO-2H-PYRAN and; 4-METHYL-2-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-3,6-DIHYDRO-2H-PYRAN

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 January to 05 February 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP study conducted in compliance with OECD Guideline No. 404 with deviations: details on feeding and environmental conditions not reported; isomers ratio not reported

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

yes

Remarks:

details on feeding and environmental conditions not reported

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

directive n° 2004/73/EC

Deviations:

yes

Remarks:

details on feeding and environmental conditions not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2007-01-11 / Signed on 2007-02-21

Test material

Test material information

Constituent 1

Reference substance name:

4-METHYLENE-2-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-TETRAHYDRO-PYRAN

Cas Number:

947237-93-6

Molecular formula:

C15 H24 O

IUPAC Name:

4-METHYLENE-2-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-TETRAHYDRO-PYRAN

Constituent 2

Reference substance name:

4-METHYL-6-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-3,6-DIHYDRO-2H-PYRAN

Cas Number:

947237-84-5

Molecular formula:

C15 H24 O

IUPAC Name:

4-METHYL-6-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-3,6-DIHYDRO-2H-PYRAN

Constituent 3

Reference substance name:

4-METHYL-2-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-3,6-DIHYDRO-2H-PYRAN

Cas Number:

947237-75-4

Molecular formula:

C15 H24 O

IUPAC Name:

4-METHYL-2-(2,2,3-TRIMETHYL-CYCLOPENT-3-ENYLMETHYL)-3,6-DIHYDRO-2H-PYRAN

Test material form:

liquid

Details on test material:

- Physical state: Yellow liquid
- Storage condition of test material: Room temperature, protected from direct sun light

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).
- Weight at study initiation: 2.25-2.85 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: No data
- Water: No data
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-22 °C
- Humidity: 30-70 %
- Air changes: No data
- Photoperiod: No data

IN-LIFE DATES: 16 January to 05 February 2007

Test system

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Test item was applied, as supplied.

Duration of treatment / exposure:

4 hours

Observation period:

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

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.

TEST SITE
- Area of exposure: Undamaged skin area of the right flank of each animal
- Type of wrap if used: Patch was secured in position with a strip of surgical adhesive tape.

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

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 4 to 14.

SCORING SYSTEM:
- Method of calculation: Skin irritant reaction was scored as per Draize scale 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:

1.7

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

probability of mild irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

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:

1.7

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

probability of mild 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:

1.7

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

probability of mild irritation

Irritant / corrosive response data:

- 24 hours after the test item application, on the treated area, a very slight to well definite erythema associated with a very slight to slight oedema was observed.
- The oedematous reactions were totally reversible between the 5th and the 7th day of the test and the erythematous reactions were totally reversible between the 7th and the 8th day of the test.
- On the cutaneous structure, it was recorded a dryness from the 3rd day of the test in 2 animals and from the 5th day of the test in the third animal. The skin recovered a normal aspect between the 11th and the 14th day of the test in two animals but the dryness was still registered the last day of the test (D14) in the last one.

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
		A7944/Female	A7946/Female	A7947/Female
Erythema/Eschar formation	1 h	1	2	2
	24 h	1	2	2
	48 h	2	2	2
	72 h	2	2	2
	Day 4	2	-	-
	Day 5	1	-	-
	Day 6	0	1	0
	Day 7	0	0	0
	Total (24, 48 and 72 hours)	5	6	6
	Mean (24, 48 and 72 hours)	1.7	2.0	2.0
Oedema formation	1 h	2	2	2
	24 h	1	2	2
	48 h	1	2	2
	72 h	1	1	1
	Day 4	0	-	-
	Day 5	0	-	-
	Day 6	0	0	0
	Day 7	0	0	0
	Total (24, 48 and 72 hours)	3	5	5
	Mean (24, 48 and 72 hours)	1.0	1.7	1.7

Note:

A7944: dryness from D4 to D14

A7946: slight dryness at D2 & D3 from D10 to D12, dryness from D6 to D9

A7947: slight dryness at D2, D3 & D9, dryness from D6 to D8

Applicant's summary and conclusion

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

Under these experimental conditions, test item must not be classified according to the CLP Regulation (EC) No. 1272/2008 and 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 an undamaged skin area of the right flank of 3 female New Zealand White rabbits. On the left 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 after removal of the patch and observations were continued from Days 4 to 14. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

 

It was noted, 24 hours after the test item application, on the treated area, a very slight to well definite erythema associated with a very slight to slight oedema. The oedematous reactions were totally reversible between the 5th and the 7th day of the test and the erythematous reactions were totally reversible between the 7th and the 8th day of the test. On the cutaneous structure, it was recorded a dryness from the 3rd day of the test in 2 animals and from the 5th day of the test in the third animal. The skin recovered a normal aspect between the 11th and the 14th day of the test in two animals but the dryness was still registered the last day of the test (D14) in the last one.

The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 1.7 / 2.0 / 2.0 for erythema and 1.0 / 1.7 / 1.7 for oedema.

 

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