Acetaldehyde oxime

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: gene mutation

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

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 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster)

GLP compliance:

not specified

Type of assay:

Drosophila SLRL assay

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)

Test animals

Species:

Drosophila melanogaster

Strain:

other: Canton-S

Sex:

male

Administration / exposure

Route of administration:

oral: feed

Details on exposure:

Young adult Canton-S males (post-meiotic germ cell stages) and young adult Canton-S males of 1-2 days old (pre-meiotic germ cell stages) were exposed to 2000 ppm AAO by feeding on glass fiber filter paper that had been inundated with either the exposure or control solution. This method also results in contact exposure and inhalation of any fumes that are present. The solvent used is a 5% sucrose solution kept at a pH of 6.8 by a phosphate buffer (1:1 ratio of 4.539 g KH2PO4 per L and 5.938g Na2HPO4.2H2O per L).

Duration of treatment / exposure:

3 days

Doses / concentrations

Remarks:

Doses / Concentrations:
2000 ppm
Basis:
nominal conc.

Control animals:

yes, concurrent vehicle

Positive control(s):

ethyl methane sulfonate: post-meiotic germ cell stages
dimethylnitrosamine: pre-meiotic germ cell stages

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Genetic testing of acetaldehyde oxime in the Drosophila melanogaster sex-linked recessive lethal test indicates that it is not mutagenic in this organism. There is evidence, however, that AAO may have induced a significant level of sterility in the treated males.

Executive summary:

In the original study on post-meiotic germ cells a cluster of 8 mutants was recovered in the acetyldehyde oxime (AAO) series. In general terms, a cluster constitutes more than one lethal mutation recovered from an individual treated male. In instances where the overall mutation frequency is low, as in the present study, it is not clear that such clusters represent independent mutational events or that they result from a clone of germ cells carrying a prior formed spontaneous mutation. In the former case the mutations would be dispersed over the length of the X chromosome whereas in the latter case they would all occur at the same genetic locus. Unfortunately, the SRLR test does not possess the capability to detect which of these two alternatives is the true situation. When the cluster of 8 was considered as 8 independent events the frequency of mutations in the AAO treated series was significantly elevated above the control frequency. On the other hand, when the cluster was treated as a single prior event the effect of AAO was not significant. The equivocal nature of these data necessitated repeating the experiment. When the data of the second experiment are pooled with those of the first experiment a statistical analysis indicates that AAO did not induce a significant number of mutations. This is true whether the cluster is treated as 8 independent events or a single prior event.

In order to further substantiate that AAO is not mutagenic in higher eukaryotes it was decided to ascertain what effect, if any, it had on spermatogonial cells. These cells are considered to be at highest risk in males because they can accumulate genetic damage over the life time of the organism. Furthermore, they are physiologically different from the post meiotic germ cells in that they are continuously undergoing cell proliferation.

The data clearly show AAO to be non-mutagenic in Drosophila spermatogonial cells. An additional observation that deserves mention, however, is the fact that approximately 23% of the males on test with AAO exhibited complete sterility. This compares to a frequency of 6% in the negative control and is significant.