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The mutagenic potential of test item was investigated using Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 as tester strains. The study was performed with and without liver homogenate (S9 mix). S9 mix consisted of S9 plus cofactors. No significant cytotoxicity effects were observed, both with and without metabolic activation. No mutagen activity was recorded at any of the concentration, with any strains, both in the presence and in the absence of metabolic activation.


FURTHER INFORMATION: review of existing data



Studies conducted in vitro, as well as in vivo indicate that piperazine does not induce point of mutations or chromosomal aberration effects. However, nitroso-piperazines that can be formed by nitrosation of piperazine in vivo demonstrate genotoxic properties (in vivo DNA strand breaks and mutations) [European Chemicals Bureau, 2005].



Melamine has been considered non-genotoxic in different in vitro and in vivo tests (WHO, 2009 and EFSA, 2010]. Other studies with different endpoints (point of mutation, chromosome aberration, DNA damage, cell transformation) and with different organisms and cells were performed. The studies included the usual Ames test, micronucleus test, cytogenetics in vitro, HGPRT assay, etc. but also other less common assays such as the bioluminescence assay. The majority of the tests returned negative results. Altogether melamine is considered to be not genotoxic and not mutagenic [OECD SIDS, 1998].

The International Agency for Research on Cancer (IARC) noted that the non-DNA reactive mechanism by which melamine produced urinary bladder tumours in male rats occurred only under conditions in which calculi were produced. Therefore, Melamine is not classifiable as carcinogenic to humans (group 3), but there is sufficient evidence in rats and mice that of melamine may cause cancer to rats and mice when administration conditions may induce calculi in the bladder [IARC, 1999]. Melamine induced proliferative epithelial lesions in the urinary tract also in the absence of observed calculi, but this may be due to loss of calculi during the tissue preparation method [WHO, 2009 and EFSA, 2010].



Although limited documentation is generally available on the genetic toxicity assays reported in the literature, the negative results obtained in various assays support the lack of evidence for genetic toxicity for Sodium Tripolyphosphate in vitro and in vivo [HERA, 2003].




Estimated based on positive results for chromosomal aberrations in vivo in mice exposed to the substituted amine phosphate component and positive results for gene mutations following in vitro exposure to the piperazine component in mouse lymphoma assays. There were also positive results in vitro for DNA synthesis-inhibition in HeLa S3 cell and genetic toxicity in Escherichia coli WP2s in a microscreen assay following exposure to the substituted amine phosphate component. No data were located for the substituted amine phosphate mixture salts regarding the genotoxicity endpoint [EPA, 2014].



Environmental Protection Agency (EPA) United States. An Alternatives Assessment for the Flame Retardant Decabromodiphenyl Ether (DecaBDE). Final report. January 2014.

European Chemicals Bureau; Joint Research Centre (2005). European Union Risk Assessment Report. Piperazine CAS 110-85-0 EC: 203-808-3. 3rd Priority List Volume: 56. Office for Official Publications of the European Communities, 2005.

European Food Safety Authority (EFSA), 2010. Scientific Opinion on Melamine in Food and Feed. EFSA Panel on Contaminants in the Food Chain (CONTAM) and EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF). European Food Safety Authority (EFSA), Parma, Italy. EFSA Journal 2010; 8(4):1573.

Human & Environmental Risk Assessment (HERA) on ingredients of European household cleaning products. Sodium Tripolyphosphate (STPP) CAS: 7758-29-4. Draft, June 2003.

IARC (International Agency for Research on Cancer), 1999. Melamine. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 73, 329-338.

OECD SIDS, 1998. Melamine CAS N°: 108-78-1. UNEP Publications.

Justification for selection of genetic toxicity endpoint
Test conducted according to internationally accepted testing procedures and according to the GLP. The OECD recommended combination of strains was respected.

Short description of key information:
Not mutagen

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), for the purpose of the classification for germ cell mutagenicity, substances are allocated in one of two categories in consideration of the fact that they are:

- substances known to induce heritable mutations or to be regarded as if they induce heritable mutations in the germ cells of humans or substances known to induce heritable mutations in the germ cells of humans or

- substances which cause concern for humans owing to the possibility that they may induce heritable mutations in the germ cells of humans.

The test substance did not show reasons of concern in the test performed.

In conclusion, based on the available data the substance does not meet the criteria to be classified for genetic toxicity, according to the CLP Regulation (EC 1272/2008).