2-Butanone, peroxide

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

Basic information are available. No guideline followed.

Data source

Reference

Reference Type:

secondary source

Title:

NTP Technical report on toxicity studies of methyl ethyl ketone peroxide (CAS No. 1338-23-4) in Dimethyl phthalate (CAS No. 131-11-3) (45:55)

Author:

Zeiger, E.

Year:

1993

Bibliographic source:

NIH Publication 93-3341

Report date:

1993

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

yes

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

2-[(2-hydroperoxybutan-2-yl)peroxy]butane-2-peroxol; butane-2,2-diperoxol

EC Number:

700-954-4

Cas Number:

1338-23-4

Molecular formula:

Mixture of C4H10O4 and C8H18O6

IUPAC Name:

2-[(2-hydroperoxybutan-2-yl)peroxy]butane-2-peroxol; butane-2,2-diperoxol

Test animals

Species:

mouse

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

dermal

Vehicle:

- Vehicle(s)/solvent(s) used: Dimethyl phthalate

Details on exposure:

NA

Duration of treatment / exposure:

13-week

Frequency of treatment:

once

Post exposure period:

NA

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.357 other: mg/animal

Doses / concentrations 2

Dose / conc.:

1.19 other: mg/animal

Doses / concentrations 3

Dose / conc.:

3.57 other: mg/animal

Doses / concentrations 4

Dose / conc.:

11.9 other: mg/animal

Doses / concentrations 5

Dose / conc.:

35.7 other: mg/animal

No. of animals per sex per dose:

10 female and 10 male animals per dose

Control animals:

yes

Positive control(s):

none

Examinations

Tissues and cell types examined:

erythrocytes in peripheral blood samples

Details of tissue and slide preparation:

The methanol-fixed slides were stained with a chromatin-specific fluorescent dye mixture of Hoechst 33258/pryronin Y and were coded. Slides were scanned using a semi-automated image analysis system to determine the frequency of micronuclei in 10,000 normochromatic erythrocytes (NCEs) and 2000 polychromatic erythrocytes (PCEs) for each of 10 males and 10 females per dose group.

Evaluation criteria:

The criteria of Schmid (1976) were used in defining micronuclei, with the additional requirement that micronuclei exhibit the characteristic fluorescent emissions of DNA. The percentage of PCEs among the total erythrocyte population was also determined.

Statistics:

Log transformation of the normochromatic erythrocyte (NCE) data, and testing for normality by the Shapiro-Wilk test, and for heterogeneity of variance by Cochran`s test, were performed before statistical analyses. The frequency of micronucleated cells among NCEs was analyzed by an analysis of variance using the SAS GLM procedure. The NCE dat for each dose group were compared with data from the concurrent DMP control using Student`s t-test. The frequency of micronucleated cells among polychromatic erythrocytes (PCEs) was analyzed by the Cochran-Armitage trend test, and individual dose groups were compared to the concurrent DMP control by Kastenbaum- Bowman`s (1970) binomial test. The percentage PCE among total erythrocytes was analyzed by an analysis of variance on ranks (classed by sex) and invidual dose groups were compared with concurrent DMP control using a t-test on ranks.

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not examined

Additional information on results:

RESULTS OF DEFINITIVE STUDY
- Appropriateness of dose levels and route: Mice of the 2 highest dose groups were not evaluated for mutagenicity due to earlier termination due to severe skin lesions.

Applicant's summary and conclusion

Conclusions:

No increase was observed in frequency of micronucleated erythrocytes in peripheral blood samples obtained from male and female mice at the end of the 13-week dermal toxicity study.

Executive summary:

The potential of methyl-ethylketone peroxide in DMP to induce micronuclei in the peripheral blood of mice was investiged after a 13 week dermal exposure of 0.357 to 3.57 mg methyl-ethylketone peroxide/animal. At this concentration severe skin damage was obsered. Thus it can be assumed that the test item became systemically available. No increase was observed in frequency of micronucleated erythrocytes in peripheral blood samples obtained from male and female mice at the end of the 13-week dermal study.