Registration Dossier

Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1971

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
DMA was investigated on male Wistar rats weighing 150-200 g. These were subjected to long-term poisning by inhalation in 100-liter chambers, predetermined vapor concentrations being maintained around the clock for 3 month.
GLP compliance:
no
Remarks:
The study was conducted prior to the adoption of the OECD guidelines
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
not reported

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
inhalation
Vehicle:
not applicable
Details on exposure:
Rats were exposed by inhalation in 100-L chambers
Duration of treatment / exposure:
15 and 90 days
Frequency of treatment:
daily
Post exposure period:
no
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/m³ air (nominal)
Dose / conc.:
0.5 mg/m³ air (nominal)
Dose / conc.:
1 mg/m³ air (nominal)
No. of animals per sex per dose:
no data
Control animals:
yes, sham-exposed

Examinations

Tissues and cell types examined:
bone marrow cells
Details of tissue and slide preparation:
The preparation for cytological investigation were prepared by the method of Ford and Woolam (Ford C.E. and Woolam D.H. Stain technology, Vol.38, p.271, 1963).
Evaluation criteria:
The incidence of structural chromosome breakages and aneuploidy, recorded in metaphases of marrow cells, was used as the criterion of a mutagenic effect. The control was provided by the incidence of similar breakages in the marrow of intact rats of the same age and sex, maintained under identical conditions.
Statistics:
Student's test.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
not examined
Additional information on results:
The incidence of cells with structural chromosome breakages was similar to that in the control preparations (0-2%), and was independent of the duration of poisoning or the concentration of DMA. Analysis of the chromosome count in the same cells revealed that the incidence of aneuploid cells in the experimental animals was somewhat higher than in the controls, for both DMA concentrations and at various times after the beginning of exposure. Statistically significant differences from the controls (p < 0.01) were detected only after 3 month' poisoning, for both DMA concentartions. The incidence of aneuploid cells in the marrow after 90 days poisoning was nearly double that after 15 days poisoning. The significant increase in the incidence of aneuploidy with both DMA concentrations and after different poisoning periods was due to both hypoploid and hyperploid cells.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
DMA did not produce cytologically detectable chromosome breakages.
Executive summary:

Male Wistar rats were exposed to 0.5 and 1 mg/cm³ dimethylamine via continuous inhalation for 15 and 90 days. 50 to 100 bone marrow cells were scored per animal. The incidence of cells with chromosomal breakage was did not exceed controls (0 -2%) in any experimantal variant but the incidence of aneuploid cells was significantly higher at both concentrations after 90 days. No decrease in mitotic activity was observed.