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Toxicological information

Genetic toxicity: in vivo

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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Well executed and reported study subjected to peer review and conducted according to modern standards, including GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Principles of method if other than guideline:
Smears were prepared from peripheral blood samples obtained by cardiac puncture from dosed and control mice exposed to t-BP for 13-weeks [via gavage] at the time of terminal kill. Slides were stained with Hoechst 333258/pyronin Y (MacGregor et al., 1983). At least 10000 NCE and 2000 PCE from each animal were scored for micronuclei.
GLP compliance:
yes
Remarks:
The t-BP studies were performed in compliance with FDA Good Laboratory Practices regulations (21 CFR 58). The Quality Assurance Unit of Battelle Columbus Laboratories performed audits and inspections of protocols, procedures, data, and reports throughout
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
t-BP used in these toxicity studies was manufactured by Penwalt Corporation (Lucidol Division, Buffalo, NY); the chemical was identified by NMR, infrared, and ultraviolet spectroscopy. Cumulative data derived from iodometric titration, elemental analysis, HPLC, and thin layer chromatography indicated a purity of > 98.8%. The bulk chemical was stored at room temperature, protected from light. Quantitative reanalyses were performed; no degradation of the material was evident.

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
B6C3F1 mice used in the 13-week study were produced under strict barrier conditions at Simonsen Laboratories, Inc. (Gilroy, CA). Animals were progeny of defined, microflora-associated parents that were transferred from isolators to barrier-maintained rooms. Rats and mice were shipped to the study laboratory at 4 to 5 weeks of age, quarantined there for 11 days, and placed on study at approximately 6 weeks of age. Blood samples were collected and the sera analyzed for viral titers from 5 animals per sex at study start and termination in the 13-week studies. Data from 12 viral screens performed in mice showed that there were no positive antibody titers (Boorman et al., 1986; Rao et al., 1989). Diet: NIH 07 pelleted feed and water, ad libitum. Animal Room Environment: Temp: 68-75°F; relative humidity: 35-65%; fluorescent light 12 h/d; 12-15 room air changes/h. Time Held Before Study: 11 d. Age When Placed on Study: 6 wks

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
t-butyl perbenzoate: 0, 30, 60, 125, 250, 500 mg t-butyl perbenzoate per kg body weight in deionized water by gavage.

Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 30, 60, 125, 250, 500 mg t-butyl perbenzoate per kg body weight
Basis:
other: as administered via gavage
No. of animals per sex per dose:
10 males; 10 females per dose
Control animals:
yes, concurrent vehicle
Positive control(s):
None reported in source document.

Examinations

Tissues and cell types examined:
Smears were prepared from peripheral blood samples obtained by cardiac puncture of dosed and control animals at the time of terminal kill. At least 10000 NCE and 2000 PCE from each animal were scored for micronuclei.
Details of tissue and slide preparation:
Smears were prepared from peripheral blood samples obtained by cardiac puncture of dosed and control animals at the time of terminal kill. At least 10000 NCE and 2000 PCE from each animal were scored for micronuclei.
Evaluation criteria:
Cochran-Armitage linear regression of proportions for PCE's or linear contrasts from Analysis of Variance for NCE's.
Statistics:
Cochran-Armitage linear regression of proportions for PCE's or linear contrasts from Analysis of Variance for NCE's.

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Additional information on results:
Following 13-weeks of gavage exposure to t-Butyl Perbenzoate, via gavage, no significant elevation in the frequency of micronucleated erythrocytes was observed in peripheral blood samples taken from either male or female mice via cardiac puncture.

Any other information on results incl. tables

See p B-7 of source report.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Following 13-weeks of gavage exposure to t-Butyl Perbenzoate, via gavage, no significant elevation in the frequency of micronucleated erythrocytes was observed in peripheral blood samples taken from either male or female mice via cardiac puncture.
Executive summary:

Following 13-weeks of gavage exposure to t-Butyl Perbenzoate, via gavage, no significant elevation in the frequency of micronucleated erythrocytes was observed in peripheral blood samples taken from either male or female mice via cardiac puncture.