(2E)-2-methyl-3-(4-methylphenyl)prop-2-en-1-ol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28-09-2011 to 18-10-2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

Justification for type of information:

Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2E)-2-methyl-3-(4-methylphenyl)prop-2-en-1-ol

EC Number:

700-548-7

Cas Number:

56138-10-4

Molecular formula:

C11H14O

IUPAC Name:

(2E)-2-methyl-3-(4-methylphenyl)prop-2-en-1-ol

Details on test material:

- Physical state: Waxy solid at temperature < 23°C and liquid at temperature > 23°C
- Storage condition of test material: In refrigerator (2-8°C) in the dark under nitrogen
- Other: white waxy solid at temperature < 23°C and clear colourless liquid at temperature > 23°C

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

Hsdlf: NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Recognised Supplier
- Age at study initiation: 23 to 27 weeks
- Weight at study initiation: 3608 to 3802 g
- Housing: Individually housed in cages with perforated floors, with shelters and cage enrichment
- Diet (ad libitum): Global Diet 2030 (Recognised Supplier); provided ad libitum (approximately 100 g per day)
- Water (ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0 (actual: 19.1 to 22.0°C)
- Humidity (%): 40 to 70 (actual: 43 – 87%)
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: 28-09-2011 To: 18-10-2011

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL. The test item was in a fluid state at the time of weighing, it was not heated and the test item was applied undiluted.
- Concentration (if solution): Not applicable.

VEHICLE
- Amount applied: Not applicable. The test item was in a fluid state at the time of weighing, it was not heated and the test item was applied undiluted.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours (initial observation); additional observations are made daily up to Days 7 and 14 to assess the reversibility of skin reactions (as appropriate).

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Dorsal (2 cm x 3 cm metalline patch secured with adhesive tape)
- % coverage: Not reported
- Type of wrap if used: metalline patch secured with adhesive tape and elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: Four hours after the application, the dressing was removed and the skin cleaned of residual test item using tap water.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 1 hour, 4 hours, 24 hours, 48 hours and 72 hours. Additional observations daily up to 7 or 14 days, as appropriate

SCORING SYSTEM: Draize Scale:
- Method of calculation:
Erythema and eschar formation:
No erythema .......................................................................................................................... 0
Very slight erythema (barely perceptible) ............................................................................... 1
Well-defined erythema ........................................................................................................... 2
Moderate to severe erythema................................................................................................. 3
Severe erythema (beet redness) *.......................................................................................... 4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the
maximum grade for erythema (= 4) is given.
Oedema formation:
No oedema ............................................................................................................................ 0
Very slight oedema (barely perceptible) ................................................................................. 1
Slight oedema (edges of area well-defined by definite raising) ............................................... 2
Moderate oedema (raised approximately 1 millimeter) ........................................................... 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Remarks:

n = 3

Time point:

other: 24, 48 , 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

n = 3

Time point:

other: 24, 48, 72 hours

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Very slight erythema and very slight oedema in the treated skin areas (maximum score = 1 for erythema and edema) in n = 3 males at all observation periods. All effects had resolved in 1 out of 3 in 24 hours. All effects had resolved in 3 out of 3 at 7 days.

Other effects:

All males showed expected gain in body weight during the study.

Any other information on results incl. tables

Table 1. Individual Scores and Mean Scores following 4-hour exposure

Skin Reaction	Reading (hours)	1# Male	#2 Male	3# Male
Erythema/Escar Formation	24	1	1	1
	48	1	1	1
	72	1	1	1
	Total	3.0	3.0	3.0
	Mean	1.0 #	1.0 #	1.0 #
Oedema Formation	24	0	1	1
	48	0	0	0
	72	0	0	0
	Total	0.0	1.0	1.0
	Mean	0.0	0.3 #	0.3 #

 # All effects reversed by day 7

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the test item is not considered to be irritating to the skin.

Executive summary:

The study was performed to OECD TG 404, EU Method B.4, US EPA OPPTS 870.2500 and Japan (JMAFF) 12 Nousan, Notification No 8147 guidelines to assess the primary skin irritancy potential of the test substance in accordance with GLP in New Zealand White rabbits. The test item was applied sequentially. Three rabbits were exposed for 4-hour by semi-occluded application of the test item to the intact clipped skin with 0.5 mL test item introduced under a 2 cm x 3 cm semi-occlusive patch. The patch was secured in position with adhesive tape and elasticated bandage. After exposure to the test item the patches were removed and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. Very slight erythema (score = 1) and very slight oedema (score = 1) was observed in the treated skin. At 72 hours two males showed erythema located at the edges of the application area. All effects had resolved within 7 days. Odema had resolved within 48 hours. Mean scores for following grading at 24, 48 and 72h were slight in erythema and eschar (score = 1) and zero in oedema (score = 0) scoring criteria. Under the conditions of the study, the test item is not considered to be a skin irritant.