1,1,2-trichloroethane

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:

weight of evidence

Study period:

2001 (April 25 to June 12)

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Results issued from reviewed document but only the summary was available.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

1,1,2-trichloroethane

EC Number:

201-166-9

EC Name:

1,1,2-trichloroethane

Cas Number:

79-00-5

Molecular formula:

C2H3Cl3

IUPAC Name:

1,1,2-trichloroethane

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 or test system 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

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw (total dose)

Remarks:

control

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw (total dose)

Remarks:

nominal

Doses / concentrations 3

Dose / conc.:

200 mg/kg bw (total dose)

Remarks:

nominal

Doses / concentrations 4

Dose / conc.:

400 mg/kg bw (total dose)

Remarks:

nominal

No. of animals per sex per dose:

5 males per dose

Control animals:

yes, concurrent vehicle

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 validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

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.