Chloroacetaldehyde

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Comparison of the Ames II and traditional Ames test responses with respect to mutagenicity, strain specificities, need for metabolism and correlation with rodent carcinogenicity

Author:

Markus Kamber et al

Year:

2009

Bibliographic source:

Mutagenesis, Vol. 24, No. 4, 359-366, 2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Ames II test results were compared to literature traditional Ames Salmonella test. Reference: NTP database.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Chloroacetaldehyde

EC Number:

203-472-8

EC Name:

Chloroacetaldehyde

Cas Number:

107-20-0

Molecular formula:

C2H3ClO

IUPAC Name:

2-chloroacetaldehyde

Test material form:

other: solution in DMSO

Details on test material:

no data

Method

Target gene:

Ames II: TA 7001-7006 plus TA98

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 98

Species / strain 2

Species / strain / cell type:

other: TA7001-7006

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

Ames II: 4.44 - 4400 µg/mL (with and without S9)

Vehicle / solvent:

Solvent: DMSO

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

2-nitrofluorene

other: 2-Aminoanthracene

Details on test system and experimental conditions:

Metabolic activation: Aroclor 1254-induced rat liver S9 fraction.
Modified liquid fluctuation test in 24-well plates.
Incubation at 737°C for 48 h.
Data aquisition in 384-well plates by an SLT Spectra Image plate reader.
The initial screen was performed without replicates. Ten compounds were chosen to be retested in triplicates
to allow for statistical analysis and to evaluate the robustness of the original screen.

Evaluation criteria:

An isolated data point > 4-fold over the baseline at the highest concentration tested could indicate the beginning of a dose-dependent response
and was therefore classified as possibly positive.

Statistics:

There was 84% agreement between the two procedures in itentifying mutagens and non-mutangens, which is equivalent to the intra- and interlaboratory reproducibility of 87% for the traditional test. The two tests also performed similarly in their predictions of rodent carcinogenicity.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

not specified

Positive controls validity:

valid

Test results 2

Species / strain:

other: TA7001-7006

Metabolic activation:

with and without

Genotoxicity:

ambiguous

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

not specified

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not determined

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not determined

Additional information on results:

Ames II: equivocal with and without S9 mix
Ames: TA98 negative with and without S9 mix, TA100 and TA1535 positive with and without metabolic activation (NTP)

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive

Chloroacetaldehyde has been found to show a positive result in the traditional Ames Salmonella test (OECD 471, NTP database).
The Ames II Salmonella mutagenicity assay procedure gave equivocal results.

Executive summary:

Ames II test results were compared to literature traditional Ames Salmonella test. Reference: NTP database.

Chloroacetaldehyde has been found to show a positive result in the traditional Ames Salmonella test (OECD 471, NTP database).

The Ames II Salmonella mutagenicity assay procedure gave equivocal results. The only strain showing a negative result in both test systems is TA98 (frameshift). Overall the result has to be evaluated as positive for the endpoint.