Octanal

Endpoint summary

Additional information

In a study conducted by Florin et al (1980), octanal was investigated for its ability to induce mutagenic activity when tested in an in vitro reverse mutagenicity test using four strains of the bacteria Salmonella typhimurium, specifically TA 98, TA 100, TA 1535 and TA 1537. The study was conducted both in the presence and absence of metabolic activation using S9 mix from Aroclor 1254 or methylcholanthrene induced rats. Under the conditions of this study, octanal was not considered to be mutagenic.

Nonanal solution in saline was added to culture medium containing freshly prepared rat hepatocytes. After 3 hours incubation the medium was removed, cultures were washed and then medium containing epidermal growth factor and bromodeoxyuridine added. After 48 hours, colcemid was added and incubated for a further 3 hours. At least 20 metaphases were scored for chromosomal aberrations. The number of chromosomal aberrations 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. There was no statistically significant increase in chromosomal aberrations in this assay.

Aldehyde solutions were added to culture medium containing freshly prepared rat hepatocytes. After 3 hours incubation medium was removed and cultures were washed twice and 5 ml of mediun containing epidermal growth factor and bromodeoxyuridine were added. 48 hours later, Colcemid was added and incubated for 3 hours. Cells were fixed and stained with DAPI for micronucleus counts. 1000 cells were scored to determine the percent cells with micronuclei. There was no significant increase in the frequency of micronuclei in micronucleated polychromatic erythrocytes. Nonanal was not found to be genotoxic in this assay.

Gene mutation was investigated by Myhr for the read-across candidate heptanal, in an in vitro gene mutation assay using mammalian cells cultures both in the absence and presence of metabolic activation (S9 mix), equivalent or similar to the OECD n°476 Guideline. In a mammalian cell gene mutation assay (TK+/-), mouse lymphoma L5178Y cells cultured in vitro were exposed to the test compound in DMSO for 4 hours at concentrations of 0.781, 37.5, 50, 75 and 100 nl/ml (without metabolic activation) and of 6.25, 100, 150, 200 and 250 nl/ml (with metabolic acitvation). Appropriate positive controls were used and showed a statistical increase in mutant colonies. The average cloning efficiencies for the negative controls varied from 72 % without activation to 68 % with activation, which demonstrated good culturing conditions for the assay. The negative control mutant frequencies were normal, and the positive control compounds induced mutant frequencies that were greatly in excess of the negative controls. The EMS positive control was slightly below the usual lower limit (300x 10-6) of the normal range, but this result (which could be due to EMS hydrolysis) was not considered to have adversely affected the assay. The test compound did not induce increases in the mutant frequeny at the TK locus in L5178Y mouse lymphoma cells with or whithout rat liver S9 microsomal activation. Without activation, concentration up to 100 nl/ml became highly toxic without causing mutant frequency increases. With activation, 250 nl/ml was moderately toxic and nonmutagenic, whereas 400 nl/ml was completely lethal.

Under the conditions of this test, the test compound did not induce increases in the mutant frequency at the TK locus in L5178Y mouse lymphoma cells with or without rat liver S9 microsomal activation.

The test material was therefore considered to be inactive in the mouse lymphoma forward mutation assay.

Investigation of five n-alkanals effects on rat and human hepatocytes indicated that no mutagenic potential was evident at dose levels likely to be experienced through normal exposure. Human hepatocytes were more sensitive than rats and nonanal, used for read across information, elicited no effect from either rats or humans.

The results of these studies performed with octanal or with structurally similar linear aldehydes indicate an absence of mutagenic activity

Justification for selection of genetic toxicity endpoint

A weight of evidence approach is used for this endpoint; a number of negative studies in vitro and in vivo are available.  Studies were performed using octanal and related linear aldehyde substances (read-across)

Short description of key information:

No evidence of mutagenicity was seen in an Ames test performed with octanal; no evidence of clastogenicity was seen in cultured hepatocytes treated with nonanal or in CHL cells exposed to decanal.  There was no increase in the frequency of micronuclei in cultured heptaocyets exposed to nonanal.  No evidence of mammalian cell mutation was seen with heptanal in a mouse lymphoma assay.  No evidence of UDS induction in vivo in hepatocytes was seen with nonanal.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification is proposed for mutagenicity in the absence of any indication of mutagenicity from any of the studies presented.