α,α-dimethylbenzyl hydroperoxide

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study (standard NTP protocol)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Standard NTP protocol

Principles of method if other than guideline:

Micronucleus analysis in NTP toxicity studies (13 weeks).

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

α,α-dimethylbenzyl hydroperoxide

EC Number:

201-254-7

EC Name:

α,α-dimethylbenzyl hydroperoxide

Cas Number:

80-15-9

Molecular formula:

C9H12O2

IUPAC Name:

1-methyl-1-phenylethyl hydroperoxide

Details on test material:

data not yet published

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

data not yet published

Administration / exposure

Route of administration:

dermal

Vehicle:

ethanol

Details on exposure:

data not yet published

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

once daily, 5 days/week

Post exposure period:

24 h

Doses / concentrations

Remarks:

Doses / Concentrations:
0.75, 1.5, 3, 6, 12 mg/kg
Basis:

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

no

Examinations

Tissues and cell types examined:

peripheral blood

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: Mice are treated in a 13 week toxicity study as part of the NTP bioassay program

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): sampling collection time is 24 h in the case of single daily exposures


DETAILS OF SLIDE PREPARATION: a blood sample from male and female mice in each dose group is obtained; slides are prepared, fixed and stained


METHOD OF ANALYSIS: 1000 mature erythrocytes ( normochromatic erythrocytes, NCEs ) are scored per animal for the presence of micronuclei (MN); the percent PCE is determined in the blood as a measure of chemical induced toxicity to the bone marrow; all data are analysed seperately for male and female mice; the type of analysis is not given (data not yet published)

Evaluation criteria:

Mean MN-NCE/100 NCE

Statistics:

A formal statistical analysis of the data is performed that includes a trend test, to determine if there is an overall increase across all doses in the frequency of cells containing micronuclei, and a pairwise comparison of each dose group to the corresponding control, to see if any dose group is statistically different from the control group in the frequency of micronucleated cells.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Vehicle controls validity:

valid

Additional information on results:

data not yet published

Any other information on results incl. tables

The trend test p-value for males was 0.264 and for females 0.777 ( a positive trend test is one in which the p-value is equal to or less than 0.025)

Males

Dose (mg/kg)	No. of animals scored	Mean MN-NCE/1000 NCE  (+- SEM)	Pairwise p-value
0*	5	2.80 (+- 0.70)
0.75	5	2.70 (+- 0.70)	0.554
1.5	5	2.90 (+- 0.29)	0.447
3	5	1.90 (+- 0.37)	0.906
6	5	2.80 (+- 0.34)	0.500
12	5	3.10 (+- 0.51)	0.348

*: vehicle control ethanol; SEM: standard error of mean

Females

Dose (mg/kg)	No. of animals scored	Mean MN-NCE/1000 NCE  (+- SEM)	Pairwise p-value
0*	5	1.90 (+- 037)
0.75	5	1.40 (+- 0.29)	0.808
1.5	5	2.10 (+- 0.29)	0.376
3	5	1.50 (+- 0.42)	0.754
6	5	1.30 (+- 0.25)	0.856
12	5	1.50 (+- 0.42)	0.754

*: vehicle control ethanol; SEM: standard error of mean

For the micronucleus frequency in any dose group to be considered significantly elevated over the control group, the p value must be equal to or less than 0.025 divided by the number of chemical treatment groups; if the number of treatment groups is 5, then the required pairwise p-value is 0.005; this adjustment in the pairwise value is a correction for multiple comparisons of the same data.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Cumene hydroperoxide given dermally for 13 weeks to mice did not induce micronuclei in the peripheral blood of the test animals

Executive summary:

Cumene hydroperoxide was tested in a Micronucleus test (Standard NTP Protocol) that is not yet published; the results are available in the Internet; the substance was applied dermally to male and female mice for 13 weeks and than the peripheral blood was tested for the presence of micronuclei; under the conditions of this test cumene hydroperoxide was negative in the in vivo mouse micronucleus test

(the data will be completed after puplication)