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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro cytogenicity / micronucleus study
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study based on scientific principles, sufficiently documented.

Data source

Reference
Reference Type:
publication
Title:
An investigation into the activation and deactivation of chlorinated hydrocarbons to genotoxins in metabolically competent human cells
Author:
Doherty, A.T. et al.
Year:
1996
Bibliographic source:
Mutagenesis, 11, 247-274

Materials and methods

Principles of method if other than guideline:
Method: other, details see below
GLP compliance:
not specified
Type of assay:
in vitro mammalian cell micronucleus test

Test material

Constituent 1
Chemical structure
Reference substance name:
1-chlorohexane
EC Number:
208-859-5
EC Name:
1-chlorohexane
Cas Number:
544-10-5
Molecular formula:
C6H13Cl
IUPAC Name:
1-chlorohexane
Details on test material:
1-Chlorohexane, not further specified.

Method

Species / strainopen allclose all
Species / strain / cell type:
other: Human lymphoblastoid cell line AHH-1 (metabolically competent: esp. CYP1A1)
Species / strain / cell type:
other: Human lymphoblastoid cell line MCL (metabolically competent: esp. CYP1A1, derived from AHH-1)
Species / strain / cell type:
other: Human lymphoblastoid cell line h2E1 (metabolically competent: esp. CYP2E1)
Metabolic activation:
without
Test concentrations with justification for top dose:
nominal: 1.0, 2.5, 5.0, and 10.0 mM (12 - 120 ug/ml)

Results and discussion

Test resultsopen allclose all
Metabolic activation:
without
Genotoxicity:
ambiguous
Cytotoxicity / choice of top concentrations:
other: 2.5 mM (30 ug/ml)
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
other: 2.5 mM (30 ug/ml)
Remarks on result:
other: other: Human lymphoblastoid cell line AHH-1 (metabolically competent: esp. CYP1A1)
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

All compounds except hexachloroethane produced dose-related increases in the

frequency of micronuclei.

Human lymphoblastoid cell line AHH-1 (metabolically competent: esp. CYP1A1):
1-Chlorohexane showed a significant increase at 5 and 10 mM, but not at 1.0 and

2.5 mM, 2.2 and 3.7-fold above background, respectively. The result proved to be

reproducible in either parallel test.

Human lymphoblastoid cell line MCL (metabolically competent: esp. CYP1A1, derived from AHH-1):

1-Chlorohexane showed a significant increase at 2.5 to 10 mM, but not at 1.0 mM,

3.3 to 4.7-fold above background, respectively. The result proved to be

reproducible in either parallel test.

Human lymphoblastoid cell line h2E1 (metabolically competent: esp. CYP2E1):

1-Chlorohexane showed a significant increase at 2.5 to 10 mM, but not at 1.0 mM,

3.2 to 4.4-fold above background, respectively. The result proved to be

reproducible in either parallel test.



The 1-chlorohexane-induced micronuclei were classified as kinetochor- and

centromer-negative types indicating a clastogenic rather than aneugenic mechanism

in mitosis.
  

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive without metabolic activation