Reaction mass of m,alpha-dimethylstyrene and p,alpha-dimethylstyrene

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 November 1994 - 18 November 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

17 July 1992

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:

dd. 16 March 1994

Test material

Test material information

Constituent 1

Reference substance name:

m,α-dimethylstyrene

EC Number:

214-394-9

EC Name:

m,α-dimethylstyrene

Cas Number:

1124-20-5

Molecular formula:

C10H12

IUPAC Name:

1-isopropenyl-3-methylbenzene

Test material form:

liquid

Details on test material:

Indentification: m/p- Isopropenyl toluene
Appearance: clear colourless liquid
Storage condition: room temperature
Purity: Not specified

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: David Percival Ltd., Moston, Sandbach, Cheshire U.K.
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: 2.32 - 2.65 kg
- Housing: Animals were housed individually in suspended metal cages
- Diet: Free access to diet (STANRAB SQC Rabbit Diet, Special Diets Services Ltd., Witham, Essex, U.K.)
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 – 19
- Humidity (%): 56 - 65
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

1 male and 2 females

Details on study design:

Study Design:
On the day before application the rabbits were 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. On the day of application a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test material was applied to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). Thereafter the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP).

Removal of test substance.
Four hours after application, the test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.

Observations:
Skin reactions were assessed at approximately 1, 24, 48, 72 hours and 7 and 14 days after the removal of the dressings and test substance.
Other effects to the skin were also recorded.

Scoring system:
Draize scale

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

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:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Well-defined erythema was noted at all treated skin sites one hour after patch removal and up to the 72 hour observation time point. The erythema extended up to 5 cm beyond all treatment sites throughout this observation period

Moderate to severe oedema was noted at all treated skin sites one hour after patch removal with slight to severe oedema at the 24-hour observation point and slight to moderate oedema at the 48 and 72-hour observation points. The oedema extended ventrally below one treatment site up to the 48 hour observation time point.

Other effects:

Crust formation extending up to 5 cm beyond all treatment sites was observed in all animals at the 7 day observation time point. Crust formation prevented accurate evaluation of erythema at one treated skin site after 7 days. Desquamation or crust formation was observed at all treated sites at the 14 day time point.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

An acute dermal irritation study was performed according to OECD guideline 404 and EU method B.4. A. Based on the results, m/p - isopropenyl toluene is classified as skin irritant (category 2) according to GHS and CLP criteria.

Executive summary:

m/p - Isopropenyl toluene was evaluated for skin irritation on 2 female and 1 male New Zealand White rabbits according to OECD test guideline 404 and EU method B.4 under GLP principles.

0.5 mL was applied semi-occlusively for 4 hours to clipped rabbit skin. Observations took place 1, 24, 48, 72 hours and 7 and 14 days after the removal of the test substance. Well-defined erythema and slight to severe oedema was observed until the 72 hour observation point. Mean scores for erythema of the 24h 48h 72h observation time points were 2.0 in all animals and mean scores for oedema were 2.0, 3.3 and 3.0. Oedema showed reversibility within 7 days and erythema was reversible within 14 days. Crust formation was observed 7 days after removal of the test substance and desquamation or crust formation was observed 14 days after removal of the test substance. Based on these results m/p - Isopropenyl toluene is classified as a skin irritant category 2 (H315) according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).