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Toxicological information

Genetic toxicity: in vivo

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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:
weight of evidence
Study period:
2001 (April 25 to June 12)
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Results issued from reviewed document but only the summary was available.

Data source

Reference
Reference Type:
secondary source
Title:
OECD SIDS 1,1,2-trichloroethane
Author:
UNEP
Year:
2000
Bibliographic source:
UNEP Publications, Tokyo

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material : 1,1,2-trichloroethane
- Analytical purity: 97.5%
- Impurities (identity and concentrations): unknown
- Lot/batch No.: 01404MQ
- Source: Sigma-Aldrich Japan Co.
- Stability under test conditions: stabilizer 2-propanol (0.5%) was used

Test animals

Species:
mouse
Strain:
other: Crj: CD-1 (ICR)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 9 weeks old


IN-LIFE DATES: From: April 25 To: june 12 2001 (48 days including preliminary study)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Olive oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:

no data
Duration of treatment / exposure:
24 and 48 hours
Frequency of treatment:
Single administration
Post exposure period:
48 days including preliminary study
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100, 200 and 400 mg/kg
Basis:
nominal in diet
No. of animals per sex per dose:
5 males per dose
Control animals:
other: methyl cellulose
Positive control(s):
cyclophosphamide

Examinations

Tissues and cell types examined:
bone marrow
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
In preliminary experiments (5 males and 5 females per dose: 100, 200, 400 and 600 mg/kg), the MTD was determined to be 600 mg/kg without clear sex differences.


DETAILS OF SLIDE PREPARATION:
Staining of bone marrow cells was performed using acridine orange fluorescence dye on slide glass
Evaluation criteria:
no data
Statistics:
The incidences of micronucleated polychromatic erythrocytes in negative control group and positive control group were analyzed whether they were within the range of the background variance. The significances between the treatment and negative control groups were analyzed by Fisher's exact test, following to Bonderroni's correction. Dose dependency was analyzed by Cochran-Armitage trend test.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Remarks:
This chemical did not induce micronuclei in bone marrow cells up to 400 mg/kg (the maximum tolerated dose), although it suppressed their proliferation at 400 mg/kg
Toxicity:
no effects
Remarks:
Toxic dose > 400 mg/kg
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Additional information on results:
See remarks on results

Any other information on results incl. tables

- The preliminary study had revealed that 1,1,2-trichloroethane induced hypoactivity in mice at doses of 400 mg/kg and above.

- Statistical results: No significant changes between negative control group and any chemical treatment group.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
No increase of micronucleated polychromatic erythrocyte counts in 2000 polychromatic erythrocytes in bone marrow cells were observed in any dose groups at 24 and 48 hours after administration. Based on these results, 1,1,2-trichloroethane was considered not genotoxic in vivo.
Executive summary:

To elucidate the genotoxic potential of 1,1,2-trichloroethane in vivo, a mammalian erythrocyte micronucleus test according to OECD test guideline 474 was conducted. 1,1,2-trichloroethane was administered by gavage in olive oil to male CD-1 mice at 100, 200 and 400 mg/kg bw, based on severe toxicity at 600 mg/kg and no sex differences on the toxicity in a previous range-finding study. The number of micronucleated PCEs in 2000 PCEs of bone marrow cells was counted at 24 and 48 h after the administration.

The 1,1, 2-trichloroethane exposed male mice showed low locomotor activity at 400 mg/kg.

Cyclophosphamide, a positive control, induced significant increase of micronucleated PCEs. No increase in the number of micronucleated PCEs in bone marrow cells were observed both 24 and 48 h after administration in any treated groups.