Zinc di(acetate)

Endpoint summary

Additional information

GENETIC TOXICITY IN VITRO:

Weight of evidence: Experimental and estimated data.

Zinc acetate has been analyzed in four short-term mutagenicity assays (Thompson et al., 1989). In the Salmonella assay (with or without hepatic homogenates), zinc acetate was not mutagenic over a dose range of 50-7200μg/plate. In the mouse lymphoma assay, zinc acetate gave a dose-dependent positive response with or without metabolic activation; the mutation frequency doubled at 10μg/mL. In the Chinese hamster ovary cell in vitro cytogenetic assay, zinc acetate gave a dose-dependent positive response with or without metabolic activation, but the presence of hepatic homogenates decreased the clastogenic effect. Zinc acetate was not positive in the unscheduled DNA synthesis assay in rat hepatocytes over a dose range of 10-1000μg/mL.

In the Mammalian Chromosome Aberration Test of zinc acetate(performed by Gasiorek et al)was performed with human lymphoblastoid cells (TK6). The exposure of unstimulated human lymphocytes to the zinc acetate did not produce a clastogenic effect but in the study performed by Santra, zinc acetate dihydrate, the clastogenic effects was observed, particularly at 72h after inoculation at 24h.

Based on published experimental data on the analogue Phenoxyacetic acid (repoted under endpoint record 07.06.01_12 Phenoxyacetic acid), which is considered to be not mutagenic on mouse lymphoma cells, with and without metabolic activation, and applying the read-across approach, the substance Zinc Acetate is also considered to be not mutagenic under test conditions.

A Danish (Q)SAR prediction with the Multicase model was realized to estimate the mutagenic potential of Zinc acetate on mammalian cells (mouse lymphoma and HGRT (CHO): Chinese hamster ovary cell HGPRT forward mutation assay). Test substance was predicted to be not mutagenic in mammalian cells. This prediction can be used for classification and risk assessment.

The available data indicate that the genotoxicity results vary widely. Conflicting results have been found. The genetic toxicity results are used for predicting either possible carcinogenic effects or toxicity to reproduction. As showed in chapters: 7.7 and 7.8 substance is not a carcinogen and has not toxic effects for reproduction.

The presented results have to be discussed with overall existing knowledge presented by official world bodies.

According to WHO, exposure to zinc does not increase mutation frequencies in the majority of bacterial or mammalian cell culture test systems. The weight of evidence from the in vitro and in vivo genotoxicity tests supports the conclusion that zinc, notwithstanding some positive findings at chromosome levels at elevated doses, has no biologically relevant genotoxicity activity (reviewed by Walsh et al., 1994; WHO, 2001).

This conclusion has also been cited in EU document “Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Zinc” (05/03/2003). The weight of evidence from thein vitro and in vivo genotoxicity tests supports the conclusion that zinc, notwithstanding some positive findings at chromosome levels at elevated doses, has no biologically relevant genotoxicity activity (reviewed by Walsh et al., 1994; WHO, 2001).

Justification for selection of genetic toxicity endpoint
Secion 7.6.1 information

Short description of key information:
Genetic toxicity in vitro:
Weight of evidence: Experimental data provided on bacterial tests, chromosome aberration test, mammalian cell gene mutation assay, and DNA damage and repair assay. Estimated data on Zinc Acetate from Danish (Q)SAR database on mammalian cell gene mutation.
Officilal bodies conclusion that zinc, notwithstanding some positive findings at chromosome levels at elevated doses, has no biologically relevant genotoxicity activity.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the information from studies and statements of autrorities on toxicity of zinc the substance is non classified.