2-Methoxy-4-methylphenyl methyl carbonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10-01-2012 to 20-01-2012

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

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: July 2011; signature: August 2011

Test material

Test material information

Constituent 1

Reference substance name:

2-methoxy-4-methylphenyl methyl carbonate

EC Number:

700-673-7

Cas Number:

132638-45-0

Molecular formula:

C10H12O4

IUPAC Name:

2-methoxy-4-methylphenyl methyl carbonate

Test material form:

solid

Details on test material:

- Physical state: Extremely pale yellow crystalline solid
- Storage condition of test material: Approximately 4°C in the dark, under nitrogen

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: 12 to 20 weeks
- Weight at study initiation: 2.08 to 2.54 kg
- Housing: Individually housed in suspended cages.
- Diet (ad libitum): 2930 Teklad Global Certified Rabbit diet (Recognised Supplier); provided ad libitum
- Water (ad libitum): mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: 10-01-2012 To: 20-01-2012

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5g
- Concentration (if solution): 0.5g test material was moistened sufficiently with 0.5 mL distilled water.

VEHICLE
- Amount applied: 0.5 ml

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours - 1 male
4 hours - 2 males

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
- Type of wrap if used: semi-occlusive (2.5 cm x 2.5 cm cotton gauze patch secured with surgical adhesive tape)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours. Earlier if appropriate based on observations.

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 1 male: Immediately, 3 minutes, 1 hour, 4 hours, 24 hours, 48 hours and 72 hours. Additional observations daily up to 7 or 14 days, as appropriate ; 2 males: Immediately, 1 hour, 24 hours, 48 hours and 72 hours. Additional observations daily up to 7 or 14 days, as appropriate.

SCORING SYSTEM: Draize Scale:
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) to slight eschar formation (injuries in depth) _______ 4

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 millimetre) _______________________________ 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) ___4
Any other skin reactions and clinical signs of toxicity, if present, were also recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 , 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 8

Irritation parameter:

other:

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No evidence of skin irritation was noted (maximum score = 0 for erythema and edema) in n=3 males at all observation periods.

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	0	0	0
	48	0	0	0
	72	0	0	0
	Total	0.0	0.0	0.0
	Mean	0.0	0.0	0.0
Oedema Formation	24	0	0	0
	48	0	0	0
	72	0	0	0
	Total	0.0	0.0	0.0
	Mean	0.0	0.0	0.0

 

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.

Executive summary:

The study was performed to OECD TG 404 and 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. Initially, one male for 3-minute, 1-hour and 4-hour by semi-occluded application to the intact rabbit skin with 0.5 g test item moistened with 0.5 mL water introduced under a 2.5 cm x 2.5 cm cotton gauze patch on the clipped skin. The patch was secured in position with a strip of surgical adhesive tape. After exposure to the test substance, the patches were removed and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. No effects were noted in one male between 3-minutes and 4-hour application and no effects were noted up to 72 hours observation. Subsequently, two further males were similarly treated by 4-hour introduction to the test item. The result was that no effects were noted following 4-hour application. A single 4-Hour, semi occluded application of the test item to the intact skin of three rabbits produced no erythema or oedema after patch removal in the observation period up to 72 hours . No corrosive effects were noted. Mean scores for following grading at 24, 48 and 72h were zero (score = 0) in erythema and eschar and in oedema scoring criteria. Under the conditions of the study, the test item is not considered to be a skin irritant.