4-isopropyl-m-cresol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From May 28 to June 20, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline No. 404 without any deviation.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on July 10, 2012/ signed on November 30, 2012)

Test material

Test material information

Constituent 1

Reference substance name:

4-isopropyl-m-cresol

EC Number:

221-761-7

EC Name:

4-isopropyl-m-cresol

Cas Number:

3228-02-2

Molecular formula:

C10H14O

IUPAC Name:

4-isopropyl-m-cresol

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): Parathymol P16029
- Physical state: White crystalline solid
- Storage condition of test material: Room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.66-3.40 kg
- Housing: Animals were housed individually in suspended cages.
- Diet: Food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 15 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From May 28 to June 20, 2014

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: test item moistened sufficiently with 0.5 mL of distilled water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- For the purpose of the study the test item was ground to a powder prior to application.

Duration of treatment / exposure:

First animal: 3 minutes, 1 and 4 h
Second and third animal: 4 h

Observation period:

1, 24, 48 and 72 h after the removal of the patch

Number of animals:

3 males

Details on study design:

PRETRAEATMENT
- On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

TEST SITE
- Area of exposure: Dorsal/flank area
- Type of wrap if used: Test material moistened sufficiently with 0.5 mL distilled water to achieve a paste, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch. Each patch was secured in position with a strip of surgical adhesive tape.
- To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): One patch was removed at each of three time points: 3 minutes, 1 and 4 h after application of test material. Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 3 minutes, 1 and 4 h

SCORING SYSTEM: Draize scale, as described in OECD Guideline No. 404

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean 24, 48 and 72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: mean 24, 48 and 72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean 24, 48 and 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No evidence of skin irritation was noted during the study.

Other effects:

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

Any other information on results incl. tables

Table 7.3.1/1: Mean irritant/corrosive response data for each animal at each observation time

Score at time point	Erythema (Animal no 1 / 2 / 3) Max. score 4	Oedema (Animal no 1 / 2 / 3) Max. score 4
Immediately	0 / 0 / 0	0 / 0 / 0
1 h	0 / 0 / 0	0 / 0 / 0
24 h	0 / 0 / 0	0 / 0 / 0
48 h	0 / 0 / 0	0 / 0 / 0
72 h	0 / 0 / 0	0 / 0 / 0
Average 24, 48 and 72 h	0 / 0 / 0	0 / 0 / 0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, Parathymol is not classified according to Regulation (EC) No. 1272/2008 (CLP) and Annex VI to the Directive 67/548/EEC.

Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 g of test material moistened with distilled water was applied on the clipped skin of the dorsal flank area of 3 male New Zealand White rabbits. 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 h after removal of the patch.

No evidence of skin irritation was observed following 3 minutes, 1 and 4 h exposure period. All animals showed expected gain in body weight during the study.

The individual 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.

Under the test conditions, Parathymoll is not classified according to Regulation (EC) No. 1272/2008 (CLP) and Annex VI to the Directive 67/548/EEC.

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