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Toxicological information

Genetic toxicity: in vivo

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Administrative data

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
weight of evidence
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic data given, comparable to guideline/standards

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
GLP compliance:
not specified
Type of assay:
chromosome aberration assay

Test material

Constituent 1
Details on test material:
purity: 99%

Test animals

Details on test animals or test system and environmental conditions:
All the animals were located in a room which was separate from but adjacent to the area where the exposures were conducted. They were housed individually in cages in a room with a light intensity of approximately 200 lux, a 12 h light-dark cycle, approximately 10 air changes per hour, temperature maintained at ca 22°C with extreme limits of 23.5°C and 17°C, and relative humidìty ca 50%, with extreme limits of 60% and 32% in the completed portions of the experiment.
The rats designated for cytogenetic analysis were housed in suspended polycarbonate cages measuring 24 x 18 x 41 cm with steel mesh tops and bottoms. The cages were suspended over trays lined with absorbent paper.
Food and water were freely available to the rats at all times.
The animals to be dosed were individually identified using bress ear tags bearing the animal number and suffix letter showing the compound designat. Each rat was ascribed a cage card which identified that animal by project number, animal number, sex and treatment group.

Administration / exposure

Route of administration:
inhalation: vapour
Details on exposure:
The test atmospheres were produced by bubbling dry, oxygen-free nitrogen (BOC Limited) through a liquid reservoir of butylene oxide contained in a glass washing, or Drechsel bottle immersed in a temperature controlled water bath at 28°C. The nitrogen/butylene oxide vapour mixturer so generated was ducted through a vertical stainless steel piping approximately 1.5 m long to a glass mixing vessel and diluted with filtered, compressed air. The resulting mixture of butylene oxide/air was ducted through a 3/4" ID stainless steel tube to the apex of the exposure chamber.
The atmospheres in the exposure chambers were dynamic in that they were continuously generated for a single pass through the animal holding zone,before being extracted from the bottom and ducted away for 'scrubbing'. The required atmospheric concentrations within the exposure chambers were maintained by finely regulating the flow of nitrogen and diluting air into the mixing vessels, by means of adjustable flow meters.
The chamber temperature and relative humidity were recorded at hourly intervals through the exposure period. The animals were also observed at regular intervals for the appearance of clinical signs or adverse reactions to treatment. On completion of the exposure period and purging of the chamber of test compound, the animals were removed from the exposure chamber and returened to the animal holding area. The animals were then removed from their individual compartments, observec for clinical signs, ear numbers checked, body weights recorded and returned to their cages.
Duration of treatment / exposure:
7 single exposures for 5 consecutive days
Frequency of treatment:
7 single exposures for 5 consecutive days
Post exposure period:
no data
Doses / concentrations
Doses / Concentrations:
250, 1000 ppm (0.75, 3.0 mg/l)
nominal conc.
No. of animals per sex per dose:
Control animals:
other: yes; air control group
Positive control(s):
Ethyl methanesulphonate (EMS)


A one-sided Student's t test was used on the transformed values.
This analysis was performed (a) including all abnormalities and (b) excluding cells only exhibiting gaps.

Results and discussion

Test results
Vehicle controls validity:
Negative controls validity:
Positive controls validity:
Additional information on results:
In the multiple exposure cytogenetic test, there were no indications of induction of chromosomal damage in either male or female rats exposed to 250 ppm or 1,000 ppm butylene oxide atmospheres.
On the other hand, treatment with 100 mg EMS/kg/day for 5 days induced large increases in the frequencies of cells with chromatid damage. In both male and female rats this damage included gaps as well as chromatid breaks with fragments.
In the single exposure test rats treated with ethyl methanesulphoate, there were significant increases in aberrant cell frequencies in males and females at the 6 h and 24 h sampling times and in the females at the 48 h sampling time. There was no significant response in the 48 h sampling time males. Theses responses were significant if all aberrant cells were analyzed or if cells containing only gaps were discarded. The damage was mainly to chromatids and there was a tendency for damage other than gaps to appear in the 24 h samples.
Butlyene oxide exposure groups did not show any increase in the frequency of aberrant cells except in the 6 h sample time males exposed to 1000 ppm butylene oxide. If cells only containing gaps were excluded from the analysis, then the statistical significance of the difference from the air control group was reduced.
This result with butylene oxide is probably insufficient evidence on which to base a conclucion for the clastogenic potential of this compound in vivo: the effect was small and was not observed in female rats.

Applicant's summary and conclusion

Interpretation of results (migrated information): negative

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