Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is considered as valid because it was conducted according to OECD guideline and according to GLP. The report is in Korean but the tables of results and the individual data are in English.This study was used as key study in the SIDS report (2002) and was quoted Kilimish 1 in the SIDS..

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Dibenzoyl peroxide
EC Number:
202-327-6
EC Name:
Dibenzoyl peroxide
Cas Number:
94-36-0
Molecular formula:
C14H10O4
IUPAC Name:
benzoyl benzenecarboperoxoate
Details on test material:
Benzoyl peroxide, source -- Sigma (B-2030), purity = 71.8 %

Test animals

Species:
mouse
Strain:
other: ICR (SPF)
Sex:
male
Details on test animals or test system and environmental conditions:
Age at study initiation : 7 weeks

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Vehicle : Pluronic F-68 solution (5 %)
Details on exposure:
under 10 ml/kg
Duration of treatment / exposure:
2 days
Frequency of treatment:
daily
Post exposure period:
24 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 100, 200 mg/kg b.w.
Basis:

No. of animals per sex per dose:
No. of animals per dose : 6
Control animals:
yes, concurrent vehicle
Positive control(s):
2 mg/kg of Mitomycin C

Examinations

Tissues and cell types examined:
Polychromatic erythrocytes from bone marrow
Statistics:
Chi-square test

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Remarks:
No medullar toxicity but toxic clinical effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
Range finding study (Table 4, attached dodument):
Benzoyl Peroxide was administered at dose levels of 2000, 1000, 500, 200 mg/kg to 3 rats per dose. Clinical signs and mortality were observed. At above 1000 mg/kg, all animals died 3 hours after the first administration. In the 500 mg/kg dose group, all animals died 1 day after the first dose. At 200 mg/kg, 2 of 3 animals died 2 days after the second dose. Therefore, for the micronucleus test, the highest dose was set at 200 mg/kg.

Genotoxic effects: Negative
Statistical results : Only positive control group showed statistically increased frequency of micronucleated cells (p < 0.01).
Description, severity, time of onset and duration of clinical signs : On the 2nd day, hypoactivity was observed at the dose level of 200 mg/kg.
Body weight changes by dose and sex : On the 3rd day for the sacrifice, there was a decrement of body weigth at 200 mg/kg bw

Any other information on results incl. tables

Summary of MNPCE frequency and PCE/NCE ratio by dose levels

Dose (mg/kg) Group mean Group mean frequency of
(PCE/PLE+NCE) MNPCE (per 1000)
Vehicle 0.54 1.33
50 0.57 0.75
100 0.52 0.83
200 0.45 1
Positive control 0.43 59.7

Applicant's summary and conclusion

Conclusions:
Benzoyl peroxide showed negative result in micronucleus test in vivo up to the test concentration of 200 mg/kg.
Executive summary:

An in vivo study, a mammalian erythrocytes micronucleus test, was conducted in accordance with OECD TG 474 and GLP. Benzoyl peroxide was administered once by intraperitoneal injection to male and female ICR mice at doses up to 200 mg/kg b.w. Benzoyl peroxide did not influence the incidence of micronuclei formation up to a maximum concentration of 200 mg/kg bw.