3-chloropropionyl chloride

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

3-chloropropionyl chloride

EC Number:

210-890-4

EC Name:

3-chloropropionyl chloride

Cas Number:

625-36-5

Molecular formula:

C3H4Cl2O

IUPAC Name:

3-chloropropanoyl chloride

Details on test material:

- Name of test material (as cited in study report): 3-Chlorpropionsäurechlorid
- Physical state/ appearance: Yellowish to brownish liquid
- Storage conditions: 4-6 °C

Method

Species / strain

Species / strain / cell type:

lymphocytes: human (from heparinized human venous blood)

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat S-9 mix

Test concentrations with justification for top dose:

5, 10, 20, 40 and 60 µg/mL (without activation system), 60, 125, 250, 500, 750 µg/mL (with activation system)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: culture medium

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

0.1 µg/mL

Positive control substance:

mitomycin C

Remarks:

without S-9 mix

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

5 µg/mL

Positive control substance:

cyclophosphamide

Remarks:

with S-9 mix

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: 48 hours
- Exposure duration: Without metabolic activation: 24 hours; With metabolic activattion: 24 hours (After about 3 hours of incubation at 37°C, cells were washed twice with unsupplemented culture medium and then re-incubated in complete culture medium for further 21 hours).
- Fixation time (start of exposure up to fixation or harvest of cells): 72 hours

SPINDLE INHIBITOR: colcemid

STAIN: Giemsa/Titrisol solution

NUMBER OF REPLICATIONS: 2

NUMBER OF CELLS EVALUATED: 100 metaphases

DETERMINATION OF CYTOTOXICITY: mitotic index

Evaluation criteria:

As a rule, 100 metaphases of each culture for the test substance, negative and solvent controls or 50 cells of each culture for the positive controls were analyzed for chromosome aberrations. A test substance was positive in this test if it led to a biological significant increase in the number of aberrant metaphases incl. and excl. gaps when compared to the untreated control or to the historical control.

Statistics:

The statistical evaluation of the data was carried out using the MUCHAN program system (BASF SE).
For each group the proportion of metaphases with aberrations was calculated.
A comparison of each dose group with the negative control group was carried out using Fisher's exact test for the hypothesis of equal proportions. This test was Bonferoni-Holm corrected over the dose groups separately for each time point and was performed one-sided.

Results and discussion

Test results

Species / strain:

lymphocytes: human (from heparinized human venous blood)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

According to the results of the present study, the test substance did not cause a biological significant increase in the number of aberrant metaphases incl. and excl. gaps when compared to the untreated control or to the historical control data (2.0 - 12.0% incl. gaps or 0.5 - 4.0% excl. gaps).

No differences regarding aneuploidies (hyperploid metaphases) and polyploidies between the varous dose groups and the negative control were observed.

Remarks on result:

other: all strains/cell types tested