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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No genetic toxicity study with fatty acids, C9-13-neo-, copper salts is available, thus the genetic toxicity will be addressed with existing data on the individual assessment entities copper and neodecanoate. As detailed in the RAAF report, neodecanoic is considered as representative of fatty acids, C9-13-neo-. Fatty acids, C9-13-neo-, copper salts is not expected to be genotoxic, since the two moieties copper and neodecanoic acid have not shown gene mutation potential in bacteria and mammalian cells as well as in vitro clastogenicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Copper

Copper II sulphate pentahydrate was assayed for mutation in 5-histaidine requiring strains (TA98, TA100, TA1537 and TA102) of Salmonella typhimurium, both in the presence and absence of metabolic activation by Aroclor 1254 -induced rat liver post-mitochondrial fraction (S-9) in 2 separate experiments.  Following a range finding study, two experiments were carried out with concentrations of 1.6, 8, 40, 200 and 1000 µg/l in experiment one and 50, 100, 200, 400 and 800 µg/l in experiment two. The tests were carried out in triplicate.  Both positive and negative controls were included. None of the dose concentrations in any of the test strains in either the absence or presence of S-9 resulted in an increase in revertant numbers that were statistically significant at the 1% level when analysed using a Dunnett’s test. It was therefore concluded that copper II sulphate pentahydrate was unable to induce mutation in 5 strains of S. typhimurium, when tested at concentrations extending to the toxic range, in both the absence and presence of rat liver metabolic activation system.

 

Copper II sulphate pentahydrate was tested for its ability to induce unscheduled DNA synthesis (UDS) in the livers of orally dosed male rats using an in vivo/in vitro procedure. Groups of 6 male rats were treated once with copper sulphate at 632.5 or 2000 mg/kg by oral gavage at a dose volume of 10 ml/kg. For the negative control, a further 6 male rats received purified water as a negative control at the same dose volume. Positive control animals for the 12-14 hour experiment, 6 male rats were dosed orally with 75 mg/kg 2 -acetamidofluorene, suspended in corn oil. Dimethylmitrosamine, dissolved in purified water, was the positive control for the 2-4 hour experiment.

 

Approximately 12-14 hours (experiment 1) or 2-4 hours (experiment 2) after dose administration the animals were sacrificed and the livers perfused with collagenase to provide a primary culture of hepatocytes. The net grain count, number of grains present in the nucleus, minus the mean number of grains in 3 equivalent areas of cytoplasm were determined.

 

Negative control animals gave a group mean net grain of less than 0 with no cells in repair. Group mean net grain values were increased by both positive controls to more than 5 with more than 50% of cells found to be in repair. This was consistent with historical control data.

 

Treatment with 632.5 or 2000mg/kg copper sulphate pentahydrate (equivalent to 161 or 509 mg Cu/kg) did not produce a group mean net grain value greater than -1.0 nor were any more than 1.0% cells found in repair at either dose.

 

Copper II sulphate pentahydrate was assayed in vivo in a mouse bone marrow micronucleus test at a single dose level of 447 mg/kg (113.76 mg Cu/kg) for two consecutive days to groups of 5 male and 5 female mice sacrificed 24 or 48 hours after the second administration. Both negative (purified water) and positive controls (cyclophosphamide) were included in the study. The study was conducted according to EEC Annex V test B12 guidelines and in compliance with GLP.

 

Mice treated with copper II sulphate pentahydrate exhibited frequencies of micronucleated polychromatic erthrocytes which were similar to vehicle controls at all sampling times. There were no instances of statistically significant increases in micronucleus frequency for any group receiving the test chemical at either sampling point.

 

Based on these results no classification for genetic toxicity is indicated according to the classification, labelling and packaging (CLP) regulation (EC) No 1272/2008.

 

Neodecanoate

Neodecanoic acid is not mutagenic in vitro in bacterial mutation assays (with and without metabolic activation) and was not clastogenic in a cytogenetic assay. Although a test on in vitro gene mutation in mammalian cells is not provided, the bacterial reverse mutation test covering the same endpoint did not show any sign of mutagenic potential with an without metabolic activation. This data suggests that neodecanoic acid is not genotoxic in vitro and likely not genotoxic in vivo.

No classification for genetic toxicity is indicated according to the classification, labelling and packaging (CLP) regulation (EC) No 1272/2008.

 

Fatty acids, C9-13-neo-, copper salts

Fatty acids, C9-13-neo-, copper salts is not expected to be genotoxic, since the two assessment entities copper and neodecanoic acid have not shown gene mutation potential in bacteria and mammalian cells as well as in in vitro clastogenicity. Further testing is not required. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

Justification for classification or non-classification

Fatty acids, C9-13-neo-, copper salts is not expected to be genotoxic, since the two assessment entities copper and neodecanoic acid have not shown gene mutation potential in in vitro tests. Thus, fatty acids, C9-13-neo-, copper salts is not to be classified according to regulation (EC) 1272/2008 as germ cell mutagen.