Reaction mass of tridecanal and 2-methyldodecanal and pentadecanal and 2-methyltetradecanal

Endpoint summary

Additional information

Mutagenicity in bacteria:

C13/C15 aldehyde was tested in an Ames test that was conducted according to OECD TG 471 and under GLP conditions, using Salmonella genetically manipulated strains TA 97a, TA98, TA100, TA102, and TA1535, with and without metabolic activation. The test item was dissolved in ethanol. Three independent experiments were conducted.

In the first experiment, five concentrations of the test item (5000, 1500, 500, 150, 50 µg/plate; dissolved in ethanol) were used in the plate incorporation method. Test concentrations were 150, 50, 15, 5, and 1.5 µg/plate in the second experiment, and 150, 75, 38, 19, 10, 5, and 2.5 µg/plate in the third experiment. Bacteriotoxicity was seen at 150 µg/plate and above. The number of revertants was not significantly increased with and without metabolic activation. The negative and positive controls performed as expected. Therefore, C13/C15 aldehyde was not mutagenic to bacteria (Salmonella typhimurium, strains TA 97a, TA 98, TA 100, TA 102 and TA 1535) under the test conditions (LAUS, 2010).

Chromosome damage

n-/i-C13 -C15 -aldehyde (purity 82%), diluted in DMSO, was assessed for its mutagenic potential in an in vitro micronucleus test using human lymphocytes, conducted according to OECD TG 487 and under GLP conditions. Two independent experiments with two replicates were conducted, without and with metabolic activation (S9 supernatant from induced (Phenobarbital/ß-naphtoflavone) male Wistar rat liver. The test substance concentrations were based on the results of range finding studies. The top concentrations were 2.0 µL/mL in the absence and 5.0 µL/mL in the presence of metabolic activation. The exposure period was 4 hours in the presence of metabolic activation in both experiments, and 4 and 20 hours in the experiment I and II, respectively, without metabolic activation. 2000 binucleated cells per concentration were examined for micronuclei.

The test substance was poorly soluble and precipitation was seen at low concentrations (0.00098 µL/mL and 0.313 µL/mL with/without metabolic activation, respectively, in experiment I). Marked cytotoxicity was also noted at low concentrations, e.g. 52.7% at 0.0625 µL/mL in experiment II in the absence of metabolic activation. The number of micronucleated cells was not increased after treatment with the test substance, with or without metabolic activation. The negative and positive controls performed as expected and demonstrated proper function of the test method.

Thus, n/i-C13 -C15 aldehyde is considered to be non-mutagenic in this in vitro mutagenicity test, when tested up to cytotoxic concentrations (Harlan, 2011).

Mutagenicity in mammalian cells

A structurally related substance, n-Undecanal, was tested for its genotoxic potential in mammalian cells in-vitro (Chinese hamster, V79 cells) at concentrations from 0.6 to 500 µg/mL in the presence and absence of metabolic activation. The assay was conducted according to the OECD TG 476 and under GLP conditions. Precipitation of undecanal was seen at 115 µg/mL and above. In the first experiment, cytotoxicity was seen at 7.5 and 20 µg/mL and higher in the absence of metabolic activation after a 4-hour exposure period. In the second experiment, cytotoxicity was seen at 25 µg/ml without S-9 mix (exposure period 24 hours), and at 500 µg/mL (with S-9 mix, exposure period 4 hours).

Undecanal did not increase the mutation frequency such that the evaluation criteria for rating the test substance were met. Vehicle and positive controls performed as expected and were comparable with historical control data of this laboratory. Therefore, undecanal was considered to be non-mutagenic in this HPRT assay (Harlan, 2010).

Read across from n-Undecanal is justified because unbranched and 2-methyl substituted saturated long chain aldehydes are closely related to each other. As a consequence, the biochemical/physiological and (eco) toxicological fate (ADME, irritation, sensitisation, genetic toxicity, repeated dose toxicity) is considered to be comparable.

 

Justification for selection of genetic toxicity endpoint
No study selected, since all three in vitro studies were negative

Short description of key information:
N-/i-C13/C15 aldehyde was non-mutagenic in a valid OECD TG 471 GLP study, with and without metabolic activation. N-/i-C13/C15 aldehyde was also non-mutagenic in mammalian cells (human lymphocty in vitro micronucleus test; GLP, OECD TG 487). Undecanal, a structurally closely related substance, was not mutagenic in a mammalian cell gene mutation assay (HPRT assay with Chinese hamster lung fibroblasts). This result can be read across to N-/i-C13/C15 aldehydes.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

N-/i-C13/C15 aldehydes and a closely related structure, n-undecanal, were not mutagenic in bacterial and human cell assays in vitro. Hence, classification is not required according to the criteria set in Regulation (EC) No 1272/2008.