Bis(2-chloroethoxy)methane

Genetic toxicity: in vivo

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

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1999

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

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

Test material information

Constituent 1

Reference substance name:

Bis(2-chloroethoxy)methane

EC Number:

203-920-2

EC Name:

Bis(2-chloroethoxy)methane

Cas Number:

111-91-1

Molecular formula:

C5H10Cl2O2

IUPAC Name:

1-chloro-2-[(2-chloroethoxy)methoxy]ethane

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 .