Fatty acids, C18-24, zinc salts

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No genotoxicity studies with substance Fatty acids, C18-24, zinc salts are available, thus the genetic toxicity will be addressed with existing data on the entities formed upon dissolution of substance Fatty acids, C18-24, zinc salt, namely zinc and fatty acids, C18-24.

Substance Fatty acids, C18-24, zinc salts is not expected to be genotoxic, since the two moieties zinc and fatty acids, C18-24 are considered as non genotoxic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

FATTY ACIDS, C18-24, ZINC SALTS:

No genotoxicity studies with substance Fatty acids, C18-24, zinc salts is available. However, few data on genetic toxicity of the structural analogue substance Fatty acids, C16-18, zinc salts (a bacterial (gene mutation in S. typhimurium) and an eukaryotic assay (gene mutation in S. cerevisiae), both tests negative) have been cited in EU RAR Zinc stearate (see excerpts below). Genetic toxicity will be addressed with existing data on the dissociation products zinc and fatty acids, C18-24. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)). The overall weight of the evidence from the existing in vitro and in vivo genotoxicity assays on soluble zinc substances suggests that zinc compounds do not have biologically relevant genotoxic activity. This conclusion is in line with those achieved by other regulatory reviews of the genotoxicity of zinc compounds (WHO, 2001; EU RAR, 2004, MAK, 2009). Thus, substance Fatty acids, C18-24, zinc salts is not expected to be genotoxic, since the two moieties zinc and fatty acids, C18-24 are considered as non genotoxic. This conclusion is in line with the conclusion of an EU risk assessment carried out on the structural analogue substance Fatty acids, C16-18, zinc salts (i.e. zinc stearate) within the framework of EU Existing Chemicals Regulation 793/93 (EU RAR Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II–Human Health. EUR 21168 EN (http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1):

“Some data were provided on the genotoxicity of zinc distearate. Data on other zinc compounds have also been used, based on the assumption that after intake the biological activities of the zinc compounds are determined by the zinc cation.

The available data indicate that the genotoxicity results vary widely. Conflicting results have been found, even in the same test systems. Overall, the results of the in vitro tests indicate that zinc has genotoxic potential in vitro based on positive results in mammalian test systems for gene mutations and chromosomal aberrations and on the positive in vitro UDS test.

In vivo, increases in chromosomal aberrations were found in calcium-deficient mice exposed via the diet as well as in mice with normal calcium status when dosed intraperitoneally. In mice also negative results were obtained and even at higher intraperitoneal dose levels. Rats tested negative for chromosomal aberrations after oral dosing, either via gavage or via the diet. The positive result for chromosomal aberrations in vitro is considered overruled by negative in vivo tests for this endpoint.

The positive sperm head abnormality test is considered sufficiently counter-balanced by two negative SLRL tests as well as two negative dominant lethal tests. Moreover, this sperm test is not adequately reported and without details on scoring criteria, interpretation of the observations is rather subjective. In addition, sperm head abnormalities are indicative rather than proof for genotoxicity.

Based on the available data there is insufficient ground to classify zinc as genotoxic. It should be noted that the potential to induce gene mutations was not adequately testedin vivo. However, there is no clear evidence from the available data that zinc is genotoxic in vivo and without a clear indication for carcinogenicity (see below) guidance for further testing with respect to target tissue is not available.”

Please refer to the section for the respective assessment entity for data on the moieties. In brief:

ZINC:

Overall weight of evidence suggests that zinc compounds do not have a biologically relevant genotoxic activity.

FATTY ACIDS, C18-24:

Fatty acids, are assessed as not being genotoxic.

Justification for classification or non-classification

As the two moieties of substance Fatty acids, C18-24, zinc salts do not induce genotoxic effects leading to a classification, substance Fatty acids, C18-24, zinc salts in all probability has also no potential to induce genotoxic effects.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptations, substance Fatty acids, C18-24, zinc salts does not have to be classified and has no obligatory labelling requirement for germ cell mutagenicity.