Dibenzoyl peroxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: US FDA, 21 CFR, Part 191, Hazardous substances test for eye irritants

Deviations:

yes

Remarks:

Few data on experimental conditions and no individual animal data reported

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dibenzoyl peroxide

EC Number:

202-327-6

EC Name:

Dibenzoyl peroxide

Cas Number:

94-36-0

Molecular formula:

C14H10O4

IUPAC Name:

diphenylperoxyanhydride

Test material form:

other: granules

Details on test material:

Benzoyl peroxide, purity = 78 percent, white granules

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2563-3217 grams
- Diet and Water: ad libitum

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the left eye served as the untreated control for each rabbit.

Amount / concentration applied:

Dosed used : 0.1 ml of test material was instilled into the everted lower eye lid of one eye of each rabbit.
The average weight of the test material was 111.4 (group I, 5 minute wash) and 120.7 mg (group II, 24 hours wash).

Duration of treatment / exposure:

Rinced after 5 min (Group I) and not rinced (Group II)

Observation period (in vivo):

Observation period : Eyes were examined at 1, 24, 48, 72 hours and 7 days after washing. 14 and 21 day examination were precluded by the absence of ulceration or opacity at 7 days.

Number of animals or in vitro replicates:

5 rabbits in Group I (5-min exposure) and 3 rabbits in Group II (24-hour exposure).

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: yes, following the exposur period, with a continuous stream of water over a 2 minute period.
- Time after start of exposure: 5 min ou 24 hours

SCORING SYSTEM: OECD grading
Examination were perfored 1 hour following was, then at 24 hours, 48 hours, 72 hours, 7 days, 14 days and 21 days.

TOOL USED TO ASSESS SCORE: fluorescein. The fluorescein was not used in the group 1 for examination at 48 hours and in the group 2 for scoring 1 hour and 48 hours after exposure.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, 2 and 3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: not rinced

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, 2 and 3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: not rinced

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

for the 3 animals together

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: not rinced

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

for the 3 animals together

Time point:

24/48/72 h

Score:

1.22

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: not rinced

Irritant / corrosive response data:

Group I : benzoyl peroxide produced very minor redness (conjunctivitis) and swelling (chemosis) in 1/5 and 2/5 rabbits, respectively, but it was clear in 24 hours. No corneal opacity was observed.
Group II : there was grade 1 opacity in 3/3 at 24 hours but it was clear at 48 hours. No iritis. There was grade 2 redness in 2/3 at 48 hours, degrading to grade 1 in 1/3 at 72 hours ; clear by day 7.

Any other information on results incl. tables

GROUP 1 (5 min wash):

-Cornea: no ulceration or opacity: at 1, 24, 48, 72 hours and 7 days for all the animals (5/5)

-Normal iris: at 1, 24, 48, 72 hours and 7 days: 5/5

-Conjunctivae: vessels normal at 1 and 24 hours: 4/5 (grade 1 for 1/5); and at 48, 72 hours and 7 days: normal for 5/5

-Chemosis: at 1 hour: 2/5 with no swelling, 2/5 with grade 1 and 1/5 with grade 2; at 24, 48,72 hours, and 7 days: no swelling for 5/5

GROUP 2 (24 hours wash):

-Cornea: no ulceration or no opacity for 3/3 at 1, 48 and 72 hours, grade 1 at 24 hours for 3/3 animals

- Iris: normal for all animals for all time observation

-Conjunctivae : redness

-         at 1 hour and 24 hours: grade 1 for 1/3 and grade 2 for 2/3

-         at 48 hours: grade 1 for 2/3 and grade 2 for 1/3

-         at 72 hours: vessels normal for 2/3 and grade 1 for 1/3

-         at 7 days: vessels normal for 3/3

-Chemosis: 

-         at 1 hour: grade 1 for 1/3 and grade 2 for 2/3

-         at 24 hours: grade 1 for 1/3, grade 2 for 1/3 and grade 3 for 1/3

-         at 48 hours: no swelling for 1/3, grade 1 for 1/3 and grade 1 for 1/3

-         at 72 hours: grade 1 for for 1/3 and grade 2 for 2/3

- at 7 days: no swelling for 3/3 Fluorescein examination: 3/3 positive damage at 24 hours, 1/3 at 48 hours and 0/3 after 7 days Blanching of the conjunctival tissue was observed for one animal only after one hour.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Benzoyl peroxide was neither irritating not corrosive to the eyes of albino rabbits if it was washed out within 5 minutes, but if 78 % benzoyl peroxide was not washed out until 24 hours later, it proved to be moderately irritating to rabbit eyes. It was not considered corrosive because corneal opacity lasted less than 6 days. Moreover, all the signs were reversible for 7 days.

Executive summary:

The potential of dibenzoyl peroxide to induce ocular irritation was evaluated in rabbits according to a method similar to OECD (No. 405, 24th April 2002) guideline.

A single dose of 0.1 mL of dibenzoyl peroxide (purity, 78 %) was instilled into the right conjunctival sac. The left eye was not treated and served as control.The substance was administered to 5 New Zealand White rabbits for 5 minutes, then the eye was washed. Moreover, the substance was adminstered to 3 New Zealand White rabbits for 24 hours, the eye was not washed.

Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours and 7 days after the administration of the substance. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were not calculated for each animal, but global scores for these effects were reported.

In group 1 (duration exposure: 5 minutes), benzoyl peroxide produced very minor redness (conjunctivitis) and swelling (chemosis) in 1/5 and 2/5 rabbits, respectively, but it was clear in 24 hours. No corneal opacity was observed.

In group 2 (duration exposure: 24 hours), there was grade 1 opacity in 3/3 rabbits at 24 hours ; clear in 3/3 at 48 hours. No iritis was observed. There was grade 2 redness in 2/3 at 48 hours, degrading to grade 1 in 1/3 at 72 hours ; clear by day 7. Even a clear irritative response was observed, all the signs were reversible within 7 days.

At fluorescein examination, corneal damage was observed in all animals after 24 hours, in one animal after 72 hours, and in no animal after 7 days.

Under these experimental conditions, the test item was moderately irritant when administered by ocular route to rabbits.