Reaction mass of 3-isopropyl-6-methylenecyclohexene and (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohexene and (4S)-1-methyl-4-(prop-1-en-2-yl)cyclohexene

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP study conducted in compliance with OECD guideline 404 with minor deviations: no details on test animals and environmental conditions; no details on patch material; observations not followed until the reversibility of the effects (only 7 days)

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1984

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

no details on test animals and environmental conditions; no details on patch material; observations not followed until the reversibility of the effects (only 7 days)

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(R)-p-mentha-1,8-diene

EC Number:

227-813-5

EC Name:

(R)-p-mentha-1,8-diene

Cas Number:

5989-27-5

Molecular formula:

C10H16

IUPAC Name:

(4R)-isopropenyl-1-methylcyclohexene

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

other: albino

Details on test animals or test system and environmental conditions:

None

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: intact

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

Three

Details on study design:

SCORING SYSTEM: Draize scoring system
- tested in a multi-patch study

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:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 7 days

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:

not fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

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:

not fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritant / corrosive response data:

- Desquamation from skin surface was observed in all animals on Day 7
- See table 1 for individual animal scores

Other effects:

No data

Any other information on results incl. tables

Table 1: Skin irritation data for individual rabbits

 

Rabbits No.		1*	2**	3*
Erythema	1 hour	2	2	1
	24 hours	2	2	2
	48 hours	2	2	2
	72 hours	2	2	2
	Day 7	1	2	1
Mean (24 hours + 48 hours + 72 hours)		2	2	2
Oedema	1 hour	3	4	3
	24 hours	2	2	2
	48 hours	1	2	1
	72 hours	1	2	1
	Day 7	1	3	1
Mean (24 hours + 48 hours + 72 hours)		1.33	2	1.33

* marked desquamation from skin surface after 7 days

** desquamation from skin surface after 7 days

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

d-limonene is classified as ‘R38 Irritating to skin’ according to Directive 67/548/EEC but it is not classified according to CLP Regulation (EC) No 1272/2008.

Executive summary:

In a primary dermal irritation study performed according to OECD guideline 404 and in compliance with GLP, three albino rabbits were dermally exposed to 0.5 mL of undiluted d-limonene, under a semi-occlusive patch for 4 hours to intact skin of the flank. Animals were then observed for 7 days. Irritation was scored by the method of Draize at 1, 24, 48 and 72 hours and 7 days after exposure.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2, 2, 2 for erythema score and 1.33, 2, 1.33 for oedema score. Signs of erythema and oedema, as well as desquamation from skin surface, were observed in all animals on Day 7. In this study, d-limonene was found to be skin irritant when applied topically to the rabbit.

 

Therefore, d-limonene is classified as ‘R38 Irritating to skin’ according to Directive 67/548/EEC but it is not classified according to CLP Regulation (EC) No 1272/2008.