Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1988-02-16 to 1988-05-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it is a well-documented study report following sound scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1998

Materials and methods

Principles of method if other than guideline:
Method: other: micronucleus assay of bone marrow
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Residual Aromatic Extract, Mobilsol 40 (C.T. 28) M.I.0.4.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
IN-LIFE DATES: From: 1988-02-18 To: 1988-05-24

Administration / exposure

Route of administration:
dermal
Vehicle:
None
Details on exposure:
No data reported.
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Once per day, five days per week
Post exposure period:
None
Doses / concentrations
Remarks:
Doses / Concentrations:
500, 2000 mg/kg bw/day
Basis:
other: dermal exposure
No. of animals per sex per dose:
10 per sex per dose
Control animals:
yes, concurrent no treatment
Positive control(s):
None

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: No data provided

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Bone marrow was harvested after the 13-week dosing period.

DETAILS OF SLIDE PREPARATION: Femurs were taken from five animals per sex per group with three slides made per animal. Slides were stained according to procedures of R. R. Tice, air dried, and fixed in absolute methanol for 15 minutes. After drying, slides were placed in acridine orange solution for 7 minutes, rinsed in Giordano's buffer solution for 10 minutes. Slides were randomized, and one thousand polychromatic erythrocytes and one thousand normochromatic erythrocytes were analyzed for micronucleus formation using fluorescence microscopy.

METHOD OF ANALYSIS: Bone marrow cells were analyzed for micronucleus formation.
Evaluation criteria:
If ratio of polychromatic and monochromatic erythrocytes in test animal cells did not differ from control, then cytotoxicity was not judged to be a factor in cytogenetic effects.
Statistics:
SAS ANOVA, ANOVA F Test, Tukey's Studentized Range Test, Scheffe's Test, and SAS General Linear Model were applied to the data.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Additional information on results:
Cytotoxicity was not a factor in micronucleus induction because the mean ratios of polychromatic to monochromatic in the dose groups were not significantly different from each other or the control group.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Under conditions of the study, residual aromatic extract does not induce a significant increase in micronuclei formation in bone marrow erythrocytes compared to controls.
Executive summary:

In an in vivo micronucleus study, male and female Sprague Dawley rats (10/sex/dose) were treated dermally with residual aromatic extract once daily, five days per week for 13 weeks at dose levels of 0, 500, or 2000 mg/kg/day. At the end of the 13 -week treatment period, bone marrow was harvested from the femur of 5 animals per sex per dose and analyzed for induction of micronucleus formation. There was no difference in the percentage of micronucleated cells in the treated animals versus the controls when analyzed by SAS ANOVA and SAS GLM (General Linear Model). Therefore, residual aromatic extract does not induce a significant increase in micronucleus formation over untreated controls.

This study recieved a Klimisch score of 1 and is classified as reliable without restriction because it is a well-documented study report that followed basic scientific principles.