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Toxicological information

Genetic toxicity: in vitro

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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