Octanal

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:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

no data. Paper accepted for publication 12 October 1989.

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Summary based on data published and detailed in the HPV summary for the structural analogue, nonanal. Provides supporting evidence from a similar substance, but not considered reliable enough to be used as akey study for assessment of octanal.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Principles of method if other than guideline:

In vitro cytogenetic assay in rat hepatocytes
Various investigations are presented in the paper including the in vitro assessment on primary cultures of hepatocytes from several sources - chinese hamster ovary cells, human bronchial fibroblasts, chinese hamster V79 cells and also a salmonella typhimurium bacterial assay. 4-hydroxynonenal and other reactive aldehydes produced by lipid peroxidation were shown to damage celluar DNA and hepatocytes appeared particularly sensitive to the effects. Sister chromatid exchange, micronuclei formation and bacterial cell changes were all identified as markers of cytotoxicity and genotoxicity for reactive aldehydes.

GLP compliance:

not specified

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

aliphatic aldehyde C7

IUPAC Name:

aliphatic aldehyde C7

Constituent 2

Reference substance name:

4-hydroxynonenal

IUPAC Name:

4-hydroxynonenal

Constituent 3

Reference substance name:

aliphatic aldehyde C9

IUPAC Name:

aliphatic aldehyde C9

Constituent 4

Reference substance name:

2-nonenal and nonenal

IUPAC Name:

2-nonenal and nonenal

Test material form:

solid - liquid: suspension

Remarks:

migrated information: dispersion

Details on test material:

Aldehyde solutions used in the assay - aliphatic C7-C9 aldehydes - administered as solutions in 0.9% saline in concentration range of 1-40 µM.
The assays summarised in the publication are for 4-hydroxynonenal (malonaldehyde), 2-nonenal and nonenal - nonenal is considered a read-across candidate for octanal

Method

Target gene:

chromosomal aberrations
free radicals can initiate the oxidative decomposition of cellular membranes by lipid peroxidation and various reactive aldehydes are produced intracellularly during the process. The tests included in this paper investigate cytotoxic and genotoxic effects of reactive aldehydes on primary hepatocyte cultures and includes some information on the genotoxiceffects of reactive aldehydes on isolated DNA, on eukaryotic and prokaryotic organisms

Species / strain

Species / strain / cell type:

hepatocytes: rat

Details on mammalian cell type (if applicable):

No details available

Additional strain / cell type characteristics:

not specified

Metabolic activation:

not specified

Test concentrations with justification for top dose:

0, 0.1, 1.0, 10 or 100 µM /plate equivalent to 0, 16.2, 162, 1620 or 16200 µg/plate

Vehicle / solvent:

0.9% saline

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

not specified

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium
DURATION

SPINDLE INHIBITOR (cytogenetic assays): colcemid


NUMBER OF REPLICATIONS: no data

NUMBER OF CELLS EVALUATED: at least 20 metaphases scored

Evaluation criteria:

Not stated

Statistics:

Student's T-test for independent variables used to evaluate mitotic index, chromosomal aberrations and sister-chromatid exchange

Results and discussion

Test results

Species / strain:

hepatocytes: Rats, Fischer 344 females

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Additional information on results:

At 100 µM (16200 µg/plate) there was a 32 fold increase in aberrations compared with controls but this was not statistically significant (because of the high standard deviation in the assay). There was no statistically significant increase in chromosomal aberrations in this assay.

Treatment of primary cultures of rat hepatocytes with 4-hydroxynonenal at 0.1, 1.0, 10 or 100 µM for 3 hours resulted in an increase in sister chromatid exchange, a sensitive parameter for the reactive aldehydes. 4-hydroxynonenal also increased the formation of micronuclei but effects on chromosomal aberrations were less apparent.

The effects of different structural elements of 4-hydroxynonenal were investigated by repeating the assays using 2-nonenal and nonanal. These aldehydes were not toxic to hepatocytes. 2-Nonenal increased micronuclei but nonanal had no such effect. Increases in chromosomal aberrations induced by both test materials did not achieve statistical significance. The effects of 4-hydroxynonenal were attributed to the functional group "-CH(OH)-CH=CH-CHO" and the 2-nonenal and nonanal substances were not found to be cytotoxic or genotoxic in this investigation

Remarks on result:

other: other: primary cultures of rat hepatocytes

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Nonanal was not mutagenic in this assay. The genotoxicity of reactive aldehydes was established in this paper but the functional group responsible for the hepatotoxicity amd mutagenicity effects was not present in the straight chain aldehydes 2-nonenal or nonenal.
By read across to octanal, it can be assumed mutagenic potential would be similar to nonanal.

Executive summary:

Nonanal solution in saline was added to culture medium containing freshly prepared rat hepatocytes. After 3 hours incubation the medium was removed and cultures were washed twice and then 5 ml of medium containing epidermal growth factor and bromodeoxyuridine were added. After 48 hour colcemid was added and incubated for a further 3 hours. At least 20 metaphases were scored for chromosomal aberrations. The number of chromosomal aberations was reported per diploid cell (42 chromosomes)

At 100 µM (16200 µg/plate) there was a 32 fold increase in aberrations compared with controls but this was not statistically significant (because of the high standard deviation in the assay). There was no statistically significant increase in chromosomal aberrations in this assay. Treatment of primary cultures of rat hepatocytes with 4-hydroxynonenal at 0.1, 1.0, 10 or 100 µM for 3 hours resulted in an increase in sister chromatid exchange, a sensitive parameter for the reactive aldehydes. 4-hydroxynonenal also increased the formation of micronuclei but effects on chromosomal aberrations were less apparent. The effects of different structural elements of 4-hydroxynonenal were investigated by repeating the assays using 2-nonenal and nonanal. These aldehydes were not toxic to hepatocytes. 2-Nonenal increased micronuclei but nonanal had no such effect. Increases in chromosomal aberrations induced by both test materials did not achieve statistical significance. The effects of 4-hydroxynonenal were attributed to the functional group [-CH(OH)-CH=CH-CHO] and the 2-nonenal and nonanal substances were not found to be cytotoxic or genotoxic in this investigation