Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

No information is available for trisodium citrate (CAS number 68 -04 -2). Information is available for the closely related substances, sodium dihydrogen citrate and citric acid. Information is available for citric acid (CAS number 77-92-9 ) and sodium dihydrogen citrate (CAS number 18996-35-5) from reliable studies for mutagenicity to bacteria. There is also information available from studies of lower reliability that citric acid does not cause chromosome aberrations in vitro. Information from reliable studies indicate that citric acid does not cause chromosome damage in somatic or in germ cells in vivo. A recent publication described positive results in mammalian cells, including a chromosome aberration analysis and an in vitro micronucleus assay. The micronucleus assay was chosen as key, as the method was close to the draft guideline and effects were observed.

It is considered that this positive result does not affect the overall genetic toxicity assessment of this substance as the effects seen in vitro were not observed in vivo and are not considered biologically relevant

Short description of key information:
In vitro:Gene mutation (Bacterial reverse mutation assay / Ames test): read across from sodium dihydrogen citrate: negative with and without activation in all strains tested (similar to OECD TG 471)
Cytogenicity in mammalian cells: read across from citric acid: positive for induction of micronuclei in cultured human lymphocytes without activation (similar to OECD draft TG 487)

In vivo
Mammalian Chromosome Aberration test in rat (oral gavage administration) (similar to OECD TG 475): read across from citric acid: negative
Rat dominant lethal Assay (oral gavage administration) (similar to EU 22): read across from citric acid: negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data, obtained by read-across from citric acid and sodium dihydrogen citrate, is sufficient to fulfil the information requirements for this endpoint. Information available in the public domain on tests carried out on other salts of this metal indicates that the sodium ions are not expected to contribute to the genetic toxicity of the substance. Additionally, the substance will dissociate when in solution, so the test organisms will be exposed to the citrate and the metal ions separately.

Therefore, it is possible to freely read across from one citrate salt to another and conduct the hazard assessment for this substance, trisodium citrate, on the properties of citric acid and sodium dihydrogen citrate. In vivo studies on citric acid showed no effects, so it is concluded that classification for mutagenicity is not required.