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Toxicological information

Genetic toxicity: in vivo

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
data not yet published

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals 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)