dimethyl 1,2-benzenedicarboxylate;reaction mass of: 1,2-dimethylpropylidene dihydroperoxide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 December 2001 - 18 December 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

442-480-8

EC Name:

-

Cas Number:

182893-11-4

Molecular formula:

Mixture of C5H12O4 and C10H22O6

IUPAC Name:

reaction mass of 1,2-dimethylpropylidene dihydroperoxide and dimethyl 1,2-benzenedicarboxylate

Details on test material:

Identification: Trigonox R-938
Chemical name: Methyl Isopropyl Ketone Peroxide
CASRN: Mixture of 13921-99-8, 33372-83-7, 131-11-3 and 563-80-4
Description: Clear colourless liquid
Batch: 1510-14
Test substance storage: In refrigerator in the dark
Stability under storage conditions: Stable
Expiry date: 01 January 2003

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: at least 6 weeks old
- Weight at study initiation: between 1.0 and 3.5 kg.
- Housing: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 53.5x63x38.5 cm).
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany) approx. 100 g. per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, hay (BMI, Helmond, the Netherlands) was provided twice a week.
- Water (e.g. ad libitum): Free access to tap-water. Certificates of quarterly analysis were examined and retained in the NOTOX archives.
- Acclimation period: Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 04 December 2001 - 18 December 2001

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7 and 14 days after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

Mortality/viability: twice daily
Toxicity: At least once daily
Body Weight: Day of treatment (prior to application)

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: flank
- % coverage: 10x15cm
- Type of wrap if used: The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water.

SCORING SYSTEM:
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:

all animals

Time point:

other: 24-48-72 hours

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 2

Irritation parameter:

edema score

Basis:

mean

Remarks:

all animals

Time point:

other: 24-48-72

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: reading was not possible due te severity of the effects in many cases.

Irritant / corrosive response data:

Four hours exposure to 0.5 ml resulted in severe erythema and moderate to severe oedema in the treated skin-areas of the three rabbits.
After removal of the bandage, white discolouration of the treated skin site was seen among all animals, which was considered to be a sign of (beginning) necrosis. Grey discolouration of the skin (a sign of necrosis) and eschar formation was noted at 1, 24, 48 and/or 72 hours after
exposure among all animals. In addition, scabs were noted among the animals during the observation period. At 14 days after exposure, a bald, noticeably white skin, and scaliness of the treated skin site was noted among all animals.
Due to eschar formation and scabs, oedema could not be scored at several time points during the observation period among all animals.
Since sufficient infomation was obtained and no reversibility of the effects was to be expected, the study was terminated after the 14 days observation.

Other effects:

Colouration
No staining of the treated skin by the test substance was observed.

Toxicity / Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Remarks:

Migrated information

Conclusions:

As evidence of full thickness destruction of the skin (scar formation; evidenced by the notably white skin) was obtained during the observation period, it was concluded that corrosion of the skin had occurred by dermal application of MIKP to the intact rabbit skin.

Executive summary:

Primary skin irritation/corrosion study in the rabbit (4-hour semiocclusive application).

The study was carried out based on the guidelines described in: EC Commission Directive 92169/EEC, B.4, "Acute Toxicity - Skin irritation" and OECD No.404, "Acute Dermal Irritation/Corrosion".

Three rabbits were exposed to 0.5 ml of MIKP, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours and 7 and 14 days after exposure.

Four hours exposure resulted in severe erythema and moderate to severe oedema in the treated skin-areas of the three rabbits.

After removal of the bandage, white discolouration of the treated skin site was seen among all animals, which was considered to be a sign of (beginning) necrosis. Grey discolouration of the skin (a sign of necrosis) and eschar formation was noted at 1, 24, 48 and/or 72 hours after exposure among all animals. In addition, scabs were noted among the animals during the observation period. At 14 days after exposure, a bald, noticeably white skin, and scaliness of the treated skin site was noted among all animals. Due to eschar formation and scabs, oedema could not be scored at several time points during the observation period among all animals.

Since sufficient infomation was obtained and no reversibility of the effects was to be expected, the study was terminated after the 14 days observation.

As evidence of full thickness destruction of the skin (scar formation; evidenced by the notably white skin) was obtained during the observation period, it was concluded that corrosion of the skin had occurred by dermal application to the intact rabbit skin.