2-benzyl-4-methyl-4a,5,6,7,8,8a-hexahydro-4H-benzo[d][1,3]dioxine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 October to 11 November, 2011.

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 without any deviation. The substance is adequately identified, but details on composition are missing. Therefore validation applies with restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

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)

Version / remarks:

30 May 2008.

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2010-12-07 / Signed on 2011-03-07

Test material

Test material information

Constituent 1

Reference substance name:

2-benzyl-4-methyl-octahydro-1,3-benzodioxine

EC Number:

956-606-9

Cas Number:

1373821-23-8

Molecular formula:

C16 H22 O2

IUPAC Name:

2-benzyl-4-methyl-octahydro-1,3-benzodioxine

Test material form:

liquid

Details on test material:

- Physical state: colourless liquid.
- Storage condition of test material: fridge 6°C±3°C, dark

Specific details on test material used for the study:

Date received: 20 October 2011

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: 2.31 - 2.75 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: foodstuff (SDS - C15), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: approximately fifteen changes per hour.
- Photoperiod: 12 hours light/12 hours dark.

IN-LIFE DATES: From 31 October to 11 November, 2011.

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
- 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.

Number of animals:

3 males

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 one 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 (in case of persistent reactions were observed).

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:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No cutaneous reactions (erythema and oedema) were observed wathever the examination time (1, 24, 48 and 72 hours).

Other effects:

None

Any other information on results incl. tables

Table 7.3.1/1: Individual and mean skin reactions/Erythema - Eschar formation following 4 hour exposure

Skin reaction	Observation time (following patch removal)	Individual Scores – Rabbit Number and Sex
		A1553/Male	A1604/Male	A1605/Male
Erythema/Eschar formation	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	Total (24, 48 and 72 hours)	0	0	0
	Mean (24, 48 and 72 hours)	0	0	0

Table 7.3.1/2: Individual and mean skin reactions/Oedema formation following 4 hour exposure

Skin reaction	Observation time (following patch removal)	Individual Scores – Rabbit Number and Sex
		A1553/Male	A1604/Male	A1605/Male
Oedema formation	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	Total (24, 48 and 72 hours)	0	0	0
	Mean (24, 48 and 72 hours)	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material is not classified as irritant to the skin according to the Annex I of the Regulation EC No. 1272/2008 (CLP) and to the 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 flank of 3 male New Zealand White rabbits. On the other 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, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

No cutaneous reactions (erythema and oedema) were observed wathever the examination time (1, 24, 48 and 72 hours).

The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 0.0 / 0.0 / 0.0 for erythema and 0.0/ 0.0 / 0.0 for oedema.

Therefore, the test material is not classified as irritant to the skin according to the Annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

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