Bis(4-methylbenzoyl)peroxide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 days of treatment and observation ( September 9, 1991 to September 12, 1991)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A reliability rating of K2 was given due to minor deficiencies such as the lack of inclusion of CAS number and the Certificate of Analysis of the test material in the Study report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

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)

Test material

Test material information

Constituent 1

Reference substance name:

Bis(4-methylbenzoyl)peroxide

EC Number:

407-950-9

EC Name:

Bis(4-methylbenzoyl)peroxide

Cas Number:

895-85-2

Molecular formula:

C16H14O4

IUPAC Name:

4-methylbenzoyl 4-methylbenzene-1-carboperoxoate

Test material form:

other: Solid White

Details on test material:

- Name of test material (as cited in study report): Di-(4-Methylbenzoyl)-peroxid (INTEROX-PMBP)
- Physical state: solid, white
- Analytical purity: Water damped powder 72% PMBP
- Purity test date: Not provided
- Batch No.: IR 240001
- Stability of test article: Stable
-Expiration date: November, 1991
- Stability of test article dilution: Stable in water for at least 48 hours
- Storage condition of test material: In the original container; protected from light at room temperature (approx. 20 degrees C)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

IN-LIFE DATES:
Acclimatization: September 5 to 8, 1991
Treatment/Observation: September 9 to 12, 1991
Completion: September 12, 1991
Reported: October 16, 1991

Test System: Rabbit, ChbbIbm: NZW (SPF)
Rationale: Recognized by the international guidelines as the recommended test system (e.g. OECD, EEC).
Source: BRL, Biological Research Laboratories Ltd., Wolferstrasse 4, CH-4414, Fullinsdorf
Number of animals: 1 male, 2 females
Age at start of treatment: male: 15 weeks; females: 16 weeks
Body weight at start of treatment: male: 2.8 kg; females: 2.8 kg
Identification: By unique cage number and corresponding ear tags.
Acclimatization: Four days under test conditions after veterinary examination.
Allocation: Animal Numbers, Male no. 34, and Female nos. 35 – 36


Standard Laboratory Conditions.
Air-conditioned with 10-15 air changes per hour and hourly monitored environment with a temperature of 20±3 degrees centigrade, a relative humidity between 40-70% (values above 70% during cleaning process possible), 12 hours artificial fluorescent light (approx. 100 Lux) / 12 hours dark, music during the light period.

Accommodation
Individually, in stainless steel cages (size: 35.5 x 55.5 x 45 cm) equipped with an automatic cleaning and drinking system (Dipl. Ing. W. Ehret GmbH, 0-7830 Emmendingen).

Diet
Pelleted standard Kliba 341, Batch 63/91 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum. Results of analysis for contaminants are included in the original study report.

Water
Community tap water from Itingen, ad libitum. Results of bacteriological, chemical and contaminant analyses are included in the original Study report.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
0.5 g of the test article was applied to approx. 6 sq. cm of the intact skin.

VEHICLE
The test article was applied moistened with bi-distilled water. The vehicle used, was found to be the most qualified to assure an optimum
technical application procedure of the test article.

Duration of treatment / exposure:

4 hrs

Number of animals:

three

Details on study design:

Rationale: Skin contact is one of the probable routes of human exposure.

Approximately 24 hours before treatment, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 100 square centimeters (10 cm x 10 cm). The skin of the animals was examined once, 1 day prior to test article administration. Only those animals with no signs of skin injury or irritation were used in the test.

On test day 1, 0.5 g of the test article was applied to approx. 6 cm2 of the intact skin of the clipped area. It was covered with a 3.0 cm x 3.0 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm-tap water.

Viability/Mortality and Clinical Signs : Observed dail y.
(Viability/mortality was recorded together with clinical signs on-line at the same time intervals. It is not specifically indicated in the computer system.)

Body Weights: At the start of acclimatization, day 1 of test (application day) and at termination of observation.

Irritation Scores: Four hours after the application, the dressing was removed and the skin was flushed with lukewarm tap water. The skin reaction was assessed according to the following numerical scoring system. (See under "other information on materials and methods" Section.) The skin reaction was assessed at 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test article. The corrosive properties of the test article and the staining of the treated skin area related to the test article were described and recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(#34, male)

Time point:

other: 1 hr

Score:

2

Max. score:

4

Remarks on result:

other: Well defined erythema and slight edema, whole area

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(#34, male)

Time point:

other: 1 hr

Score:

2

Max. score:

4

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(#35, female)

Time point:

other: 1 hr

Score:

1

Max. score:

4

Remarks on result:

other: Very slight erythema, edema, whole area

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(#35, female)

Time point:

other: 1 hr

Score:

1

Max. score:

4

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(#36, female)

Time point:

other: 1 hr

Score:

1

Max. score:

4

Remarks on result:

other: Very slight erythema, edema, whole area

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(#36, female)

Time point:

other: 1 hr

Score:

1

Max. score:

4

Results 7

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Remarks on result:

other: Very slight erythema, maculated

Results 8

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Results 9

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Remarks on result:

other: No abnormalities visible

Results 10

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Results 11

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

1

Max. score:

4

Remarks on result:

other: Very slight erythema, edema, maculated

Results 12

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

1

Max. score:

4

Results 13

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Remarks on result:

other: No abnormalities visible.

Results 14

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Remarks on result:

other: No abnormalities visible

Results 15

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Score:

1

Max. score:

4

Remarks on result:

other: Very slight erythema, maculated

Results 16

Irritation parameter:

edema score

Basis:

other: All 3 animals

Time point:

48 h

Score:

0

Max. score:

4

Remarks on result:

other: Zero score for all 3 animals at 48 hrs

Results 17

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(#34, male)

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

other: No abnormalities visible

Results 18

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(#35, female)

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

other: No abnormalities visible

Results 19

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(#36, female)

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

other: No abnormalities visible

Results 20

Irritation parameter:

edema score

Basis:

other: All 3 animals

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

other: Zero score for all 3 animals at 72 hrs

Irritant / corrosive response data:

RESULTS

IRRITATION: Di-(4-Methylbenzoyl)-peroxid (INTEROX PMBP) showed a primary irritation score of 0.44 when applied to healthy intact rabbit skin. Local signs (mean values from 1 hour to 72 hours) consisted of grade 0.58 erythema and grade 0.42 edema.

COLORATION: In the area of application no staining of the treated skin by pigment or coloring of the test article was observed.

CORROSION: No destructions or irreversible alterations of the treated skin were observed. No corrosive effect was evident on the skin.

Other effects:

CLINICAL SIGNS AND VIABILITY I MORTALITY: No acute clinical symptoms were observed in the animals during the test and observation period, and no mortality occurred.

BODY WEIGHTS: The body weight gain of all rabbits was similar.

Any other information on results incl. tables

The individual skin irritation scores at 1, 24, 48 and 72 hrs as well as the calculated mean scores for each animal based on 24, 48 and 72 hour observations are provided as two tables under "overall remarks, attachments" (see illustration).

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test article Di-(4 -Methy1benzoy1)-peroxid (INTEROX PMBP) is classified as not irritant to the skin of rabbits based on the EEC Council Directive,83/467/EEC,July 1983 and67/548/EEC, May 1987, Brussels, Belgium.

Executive summary:

The purpose of this primary skin irritation study was to assess the possible irritation potential when single doses of Di-(4 -Methy1benzoy1)-peroxid (INTEROX PMBP) were placed (semi-occlusive) on the skin of NZW rabbits. This study should provide a rational basis for risk assessment in man. The GLP study was conducted according to OECD 404 and EEC B4 test guidelines. A reliability rating of K2 was given due to minor deficiencies such as the lack of inclusion of CAS number and the Certificate of Analysis of the test material in the Study report. 

Local signs (mean values from 1 hour to 72 hours) consisted of grade 0.58 erythema and grade 0.42 edema. In the area of application, no staining of the treated skin by pigment or coloring of the test article was observed. No corrosive effect occurred on the treated skin of any animal at each measuring interval. Under the conditions of this experiment, Di-(4-Methylbenzoyl)-peroxid (INTEROX PMBP) was found to cause a primary irritation score of 0.44 when applied to healthy intact rabbit skin.  

According to EEC Council Directive, 83/467/EEC, July 1983 and 67/548/EEC, May 1987, Brussels, Belgium, the mean value of the scores for each type of lesion, calculated for each animal separately, is the following:  

AnimalNo. / Sex   Mean 24 - 72 hours                                                                                           

Erythema       Edema 

34 M                          0.33                0.00     

35 F                           0.00                0.00     

36 F                           0.67                0.33      

Conclusion: Based on the results described above, the test article Di-(4 -Methy1benzoy1)-peroxid (INTEROX PMBP) is classified as not irritant to the skin of NZW rabbits.