Zinc bis(benzenesulphinate)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames assay (OECD 471): non-mutagenic.

Micronucleus assay (OECD 487): positive without metabolic activation

Genetic toxicity in vivo

Description of key information

Single cell gel / comet assay has been proposed.

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

An in vitro gene mutation study in bacteria was run following OECD guideline 471 in S. typhimurium strains TA98, TA100, TA1535, TA1537 and E. coli WP2 uvrA with and without metabolic activation.

All strains were tested according to plate incorporation method in 2 experiments. Concentrations ranges were 50 - 5000 µg/plate (exp. I) and 15 - 1500 µg/plate (exp. II). Each concentration was tested in triplicate. Toxicity was evaluated in TA98 strain. Positive and negative (untreated, solvent) controls were run.

Test substance was found to be non-mutagenic to all strains with and without metabolic activation.

An in vitro micronucleus assay in mammalian cells was run according to OECD guideline 487 using peripheral human blood lymphocytes.

In the first experiment, cells were exposed at doses between 62.5 and 1000 µg/ml for 3 hours with and without metabolic activation; in the second experiment, cells were exposed at doses between 31.25 and 500 µg/ml for 23 hours without metabolic activation. Positive and negative controls were included.

Doses causing high cytotoxicity, i.e. more than 55 ± 5 %, were not used to assess genotoxic effects, i.e. doses of 500 and 1000 µg/ml were excluded.

Dose-dependent genotoxic effects were seen at 125 and 250 µg/ml without metabolic activation.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), a mutation means a permanent change in the amount or structure of the genetic material in a cell. The term ‘mutation’ applies both to heritable genetic changes that may be manifested at the phenotypic level and to the underlying DNA modifications when known.

The more general terms ‘genotoxic’ and ‘genotoxicity’ apply to agents or processes which alter the structure, information content, or segregation of DNA, including those which cause DNA damage by interfering with normal replication processes, or which in a non- physiological manner (temporarily) alter its replication.

For the purpose of classification for germ cell mutagenicity, substances are allocated to one of two categories:

 

Category 1: substances known to induce heritable mutations or to be regarded as if they induce heritable mutations in the germ cells of humans.

Category 1A: based on positive evidence from human epidemiological studies.

Category 1B: based on:

- positive result(s) from in vivo heritable germ cell mutagenicity tests in mammals; or

- positive result(s) from in vivo somatic cell mutagenicity tests in mammals, in combination with some evidence that the substance has potential to cause mutations to germ cells.

- positive results from tests showing mutagenic effects in the germ cells of humans, without demonstration of transmission to progeny; for example, an increase in the frequency of aneuploidy in sperm cells of exposed people.

 

Category 2: substances which cause concern for humans owing to the possibility that they may induce heritable mutations in the germ cells of humans, based on positive evidence obtained from experiments in mammals and/or in some cases from in vitro experiments, obtained from:

- somatic cell mutagenicity tests in vivo, in mammals; or

- other in vivo somatic cell genotoxicity tests which are supported by positive results from in vitro mutagenicity assays

 

Based on available data, i.e.:

- negative result in a gene mutation assay in bacteria

- positive result in an in vitro micronucleus assay,

the assessment on the genotoxic potential of target substance is currently inconclusive; a decision on classification under the CLP Regulation (EC 1272/2008) will be taken once further information is available.