Acetaldehyde oxime

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro DNA damage and/or repair study

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980-1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells)

GLP compliance:

not specified

Type of assay:

sister chromatid exchange assay in mammalian cells

Test material

Test material information

Constituent 1

Reference substance name:

Acetaldehyde oxime

EC Number:

203-479-6

EC Name:

Acetaldehyde oxime

Cas Number:

107-29-9

Molecular formula:

C2H5NO

IUPAC Name:

acetaldehyde oxime

Details on test material:

- test material: acetaldehyde oxime (AAO)
- source: Sigma Chemical Company
- Lot No.: 290-0490
- Purity: 99.9% pure by HPLC

Method

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Details on mammalian cell type (if applicable):

- Type and identity of media: Ham's F12 with 10% filtered FBS and 1% antibiotic/antimycotic

Metabolic activation:

with and without

Metabolic activation system:

S9 metabolic system

Test concentrations with justification for top dose:

- Experiment 1: 0, 0.01, 0.03, 0.1, 0.3 μL/mL AAO
- Experiment 2: 0, 0.0006, 0.002, 006 μL/mL AAO
- Experiment 3: 0, 0.01, 0.03, 0.1, 0.3 μL/mL AAO
- Experiment 4: 0, 0.03, 0.06, 0.09 μL/mL AAO

Vehicle / solvent:

water

Controls

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

positive controls: benzo(a)pyrene, ethylnitrosourea

Details on test system and experimental conditions:

DURATION
- Exposure duration: 0.5 - 27 h
- Fixation time (start of exposure up to fixation or harvest of cells): 27 - 29 h

SPINDLE INHIBITOR: colcemid
STAIN: bromodeoxyuridine (BrdU)

DETERMINATION OF CYTOTOXICITY
- Method: determination of dividing cells

Results and discussion

Test results

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive

Analysis of results from the sister chromatid exchange (SCE) assay in cultured mammalian Chinese hamster ovary cells indicates that acetaldehyde oxime (AAO) induces SCEs both with and without metabolic activation, and that it is somewhat more toxic or inhibitory, in terms of cell cycle progression, when used together with metabolic activation system. AAO is, however, a very weak SCE-inducer, as not even a doubling of the background SCE frequency was observed.

Executive summary:

Initial experiments were designed to determine, quite simply, whether or not acetaldehyde oxime (AAO) does or does not induce sister chromatid exchanges (SCEs) in vitro. Positive controls were not employed as there were intended to serve as preliminary, range-finding-type experiments. Low doses were employed in the activation test because previous work (conducted by other Allied personnel) had indicated an approximate 50 -fold increase in toxicity when AAO was used with the metabolic activation systems. While AAO proved to be positive with regard to SCE induction at these low doses, there was no indication of toxicity. Many second division cells were present, indicating that mitotic delay, if present, was not severe; and, in addition, very few dead, floating cells were present in the culture.

Experiment 3 re-tested AAO with the S9 activation system but employed higher doses. AAO was again positive with activation and toxicity was apparent at the highest doses.

The final experiment (No. 4) was intended to determine whether or not the small increases in SCE frequency observed with AAO are truly the result of AAO interactions with CHO DNA or might have been due to AAO toxicity, with the result that surviving cells incorporated more BrdU. It has been previously been reported that increases in the BrdU/cell ratio can increase SCE frequencies nearly 2 -fold. The experimental results indicate that in fact, while higher BrdU doses do lead to greater SCE frequencies, AAO does induce SCEs directly.

In conclusion, AAO induces SCEs both with and without metabolic activation. Metabolic activation has little or no effect on SCE induction, but does render AAO somewhat more toxic, as greater numbers of scorable mitotic cells were present at higher doses when the compound was used directly vis-a-vis use with the metabolic activation system.