O,O-tert-butyl isopropyl monoperoxycarbonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Start: 20 October 1998 End: 10 November 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

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:

O,O-tert-butyl isopropyl monoperoxycarbonate

EC Number:

219-143-7

EC Name:

O,O-tert-butyl isopropyl monoperoxycarbonate

Cas Number:

2372-21-6

Molecular formula:

C8H16O4

IUPAC Name:

tert-butoxy propan-2-yl carbonate

additive 1

Reference substance name:

Hydrocarbons, C4, 1,3-butadiene-free, polymd., triisobutylene fraction, hydrogenated

EC Number:

297-629-8

EC Name:

Hydrocarbons, C4, 1,3-butadiene-free, polymd., triisobutylene fraction, hydrogenated

Cas Number:

93685-81-5

Molecular formula:

not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)

IUPAC Name:

isododecane

Test material form:

liquid

Details on test material:

Trigonox BPIC-C75

Specific details on test material used for the study:

The specific details of the test material used for this study were as follows:

Batch: 0419804130350
Test substance storage: In refrigerator in the dark. Do not heat test substance.
Stability under storage conditions: Not indicated
Expiry date: 01 October 1999 (allocated by NOTOX, 1 year after· receipt of the test substance)
Density: 900-910 kg/ms (20°C)
The test substance was not heated above the temperature of 70°C.
Preparation: The test substance was applied undiluted as delivered by the sponsor.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Species: Albino Rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e. g. EC, OECD)
Source: Broekman Institute, Someren, The Netherlands.
Number of animals: 3 Animals of either sex.
Age and body weight: Animals used within the study were at least 6 weeks old and body weights were less than 3.5 kg.
Identification: Ear tag.

ANIMAL HUSBANDRY
Conditions:
Air-conditioned room with approximate1y 15 air changes per hour and the environment controlled with optimal conditions considered as being a temperature of 21°C and a relative humidity of 50%. Fluctuations from these optimal conditions were noted, but were considered not to have affected study integrity. Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.
Accommodation
Individually housed in labelled cages with perforated floors (Scanbur, Denmark) and equipped with an automatic drinking system (ITL, Bergen, The Netherlands). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet
Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands) approx. 100 gram per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, hay (BM, Helmond, The Netherlands) was provided once a week.
Water
Free access to tap-water diluted with decalcified water. Certificates of quarterly analysis were examined and retained in the NOTOX archives.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

The dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm^2).

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 hours.and 7, 14 and 21 days after the removal of the dressings and test substance.

Number of animals:

3 animals of either sex.

Details on study design:

Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm^2). Whenever considered necessary the treated skin areas were rec lipped at least 3 hours before the observations, to facilitate the scoring.
A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.
On test day 1, 0.5 ml of 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.
Four hours after the application, the dressing was removed and the remaining test substance removed using a tissue moistened with tap-water and subsequently a dry tissue.

OBSERVATIONS
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application).
Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours.and 7, 14 and 21 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.

The irritation was assessed· according to the following numerical scoring system.
At each observation, the highest scores given was recorded:
ERYTHEMA AND ESCHAR FORMATION
No erythema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
Very slight erythema (barely perceptible) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
We 11 defined erythema . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Moderate to severe erythema . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Severe erythema (beet redness) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
In cases 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 mm) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Severe oedema (raised more than 1 nun and extending beyond area of exposure) . . . . . . . 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

Mean score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 2

Irritation parameter:

erythema score

Remarks:

Mean score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 3

Irritation parameter:

erythema score

Remarks:

Mean score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 4

Irritation parameter:

edema score

Remarks:

Mean score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 5

Irritation parameter:

edema score

Remarks:

Mean score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.4

Max. score:

4

Reversibility:

fully reversible within: 21 days

Results 6

Irritation parameter:

edema score

Remarks:

Mean score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

Irritation
Four hours exposure to 0.5 ml of TERT·BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT resulted in moderate to severe erythema and severe oedema in the treated skin-areas of the three rabbits. In all animals, reduced flexibility of the skin, scaliness and/or bald skin were present 7 and 14 days after exposure. Bald skin remained present until termination but the skin irritation had resolved within 21 days after exposure in all animals.
Corrosion
There was no evidence of a corrosive effect on the skin.

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 2 (irritant) based on GHS criteria

Remarks:

Mean scores for erythema/edema were >=2.3-<=4.0

Conclusions:

No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75%
SOLUTION IN AROMATIC FREE MINERAL SPIRIT to the intact rabbit skin.
Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TERT·BUTYLPEROXY ISOPROPYL CARBONATE, 75%
SOLUTION IN AROMATIC FREE MINERAL SPIRIT should be labelled as: irritating to skin (R 38).

Executive summary:

Primary skin irritation/corrosion study with TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT in the rabbit (4-hour

semi-occlusive application).

The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, 8.4, "Acute Toxicity - Skin irritation· and OECD No.404, "Acute Dermal Irritation/Corrosion".

Three rabbits were exposed to 0.5 ml of TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT, applied onto clipped skin for 4

hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours and 7, 14 and 21 days after exposure.

Exposure to TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT resulted in moderate to severe erythema and severe oedema in the

treated skin-areas of the three rabbits. In all animals, reduced flexibility of the skin, scaliness and/or bald skin were present 7 and 14 days after exposure.

Bald skin remained present until termination but the skin irritation had resolved within 21 days after exposure in all animals.

No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT to the intact rabbit skin.

Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TERT-BUTYLPEROXY ISOPROPYL CARBONATE, 75% SOLUTION IN AROMATIC FREE MINERAL SPIRIT should be labelled as: irritating to skin (R 38).

The substance is classified as a skin irritant Cat 2 (H315) per “Guidance to Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging (CLP) of substances and mixtures”, Version 5, July 2017 and per UN GHS.