2-chloropropane

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, according to accepted guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Version / remarks:

1983 followed, reliability scoring based on 1997 guideline.

Deviations:

no

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

2-chloropropane

EC Number:

200-858-8

EC Name:

2-chloropropane

Cas Number:

75-29-6

Molecular formula:

C3H7Cl

IUPAC Name:

2-chloropropane

Details on test material:

- Name of test material (as cited in study report): 2-Chloropropane
- Physical state: Liquid < 36 ºC
- Analytical purity: At least 95%
- Stability under test conditions: Stability of pure test article not indicated by the sponsor. Half-life time in buffered solution (pH 7.0) at 40 ºC = 51.1 hours and at 27 ºC = 135.0 hours
- Storage condition of test material: Room temperature

Method

Species / strain

Species / strain / cell type:

lymphocytes: Human peripheral blood lymphocytes

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver microsomes (S9)

Test concentrations with justification for top dose:

Pre-experiment for toxicity at 24 hours = 1, 3, 10, 30, 100, 300, 600, and 800 µg/mL (+ and - S9)
Pre-experiment for toxicity at 48 hours = 30, 100, 300, 600, and 800 µg/mL (+ and - S9)

Chromosome aberration assay at 24 hours = 0 (solvent control), 0 (negative control), 30, 300, and 800 µg/mL (+ and - S9)
Chromosome aberration assay at 48 hours = 0 (solvent control) and 800 µg/mL (+ and - S9)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: The solvent was chosen according to its solubility properties and its non-toxicity for the cells.

Controls

Untreated negative controls:

yes

Remarks:

Assumed to be a blank control

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Ethylmethanesulfonate (- S9) and cyclophosphamide (+ S9)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 4 hours at 37 ºC
- Fixation time (start of exposure up to fixation or harvest of cells): 24 and 48 hours

SPINDLE INHIBITOR (cytogenetic assays): Colcemide

NUMBER OF REPLICATIONS: 2 cultures/dose level

NUMBER OF CELLS EVALUATED: At least 100 well spread metaphases/culture

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

Evaluation criteria:

A test article is classified as mutagenic if it induces a significantly increased aberration rate with at least one of the concentrations tested as compared with the negative control. A test article which produces no significant positive response at any test point will be regarded as non-mutagenic.

Statistics:

Chi-square test

Results and discussion

Test results

Species / strain:

lymphocytes: Human peripheral blood lymphocytes

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

>800 µg/mL precipitated in the culture medium

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

In the pre-experimental phase, scoring the mitotic index, in the absence and presence of the S9 mix even with the highest concentration, the mitotic index was not reduced as compared to the solvent and negative controls. However, higher concentrations than 800 µg/ml precipitated in the culture medium.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

With the test article 2 -chloropropane, no biologically relevant increase in the structural chromosomal aberration rate could be found when compared with the range of aberrations in the corresponding negative and solvent controls. These results were obtained at each fixation interval both in the absence and presence of S9 mix.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative