Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The data was retrieved from the NTP. Protocol and results are available online and as an appendix to NTP TR 536. No details on test substance composition. NTP study data is generally well trusted.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1999
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Principles of method if other than guideline:
- The study was performed accoding to standard NTP Protocol. The detailed protocol is presented by Shelby et al. (1993).
- Protocol and results are available online. No study report avialable.
- No data on preparation of the animals or housing and feeding conditions of the animals.
- No data on preparation of the doses.
- Signs of toxicity observed in the test animals are not reported in the data that is avialable on the NTP website. A small dose releated decline in %PCE is observed in the study. At the highest dose level a major decline in %PCE is observed and only 2 out of 5 animals survived treatment.
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance: bis(2-chloroethoxy)methane. No further information.

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
3 days
Frequency of treatment:
Daily, 24 hou intervals
Post exposure period:
Samples were taken 24 hours after last exposure
Doses / concentrations
Remarks:
Doses / Concentrations:
16.25, 32.5, 65 or 130 mg/kg
Basis:

No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Route of administration: recommended in the guideline.
- Doses / concentrations: 15 or 25 mg/kg

Examinations

Tissues and cell types examined:
Bone marrow
Evaluation criteria:
In the micronucleus test, an individual trial is considered positive if the trend test P value is less than or equal to 0.025 or if the P value for any single dosed group is less than or equal to 0.025 divided by the number of dosed groups. A final call of positive for micronucleus induction is preferably based on reproducibly positive trials (as noted above). Ultimately, the final call is determined by the scientific staff after considering the results of statistical analyses, reproducibility of any effects observed, and the magnitudes of those effects.
Statistics:
The results were tabulated as the mean of the pooled results from all animals within a treatment group, plus or minus the standard error of the mean. The frequency of micronucleated cells among PCEs was analyzed by a statistical software package that tested for increasing trend over dose groups using a one-tailed Cochran-Armitage trend test, followed by pairwise comparisons between each dosed group and the control group. In the presence of excess binomial variation, as detected by a binomial dispersion test, the binomial variance of the Cochran-Armitage test was adjusted upward in proportion to the excess variation.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Remarks:
At the high dose 3 out of 5 animals died.
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
In this in vivo study, no increases in the frequencies of micronucleated PCEs were seen in bone marrow samples from male F344 rats exposed to concentrations of 16.25 - 130 mg/kg bis(2-chloroethoxy)methane by gavage for 3 days.
Executive summary:

A in vivo micronucleus study was performed in male F344 rats according to NTP protocol (similar to OECD 474). The rats were dosed by oral gavage at doses of 16.25, 32.5, 65 or 130 mg/kg for 3 consecutive days. 24 hours after the last dose bone marrow smears were prepared, . In this in vivo study, no increases in the frequencies of micronucleated PCEs were seen in bone marrow samples from male F344 rats exposed to concentrations of 16.25 - 130 mg/kg bis(2-chloroethoxy)methane by gavage for 3 days .