Genotoxic and cytotoxic effects of triammonium citrate E380 on human peripheral lymphocytes in vitro

Triammonium citrate (TS) is widely used as an acidity regulator in the food industry, a stabilizer in pharmaceuticals, a metal-coating agent in cleaning products, and a buffering agent in water treatment and laboratory research. This study aimed to evaluate the genotoxic and cytotoxic profiles of TS through multidisciplinary methodologies to assess its safety for industrial and pharmaceutical applications. The cytotoxic effect of TS was analyzed using the CCK-8 assay in MCF-7 (human breast cancer) and NIH3T3 (mouse fibroblast) cell lines. The results showed that no cytotoxic effect was observed in both cell groups at all concentrations and times. Genotoxic potential was assessed in human peripheral lymphocytes via chromosomal aberration (CA), micronucleus (MN), and sister chromatid exchange (SCE) tests, which demonstrated no significant DNA damage or chromosomal instability compared to controls. Mutagenicity was evaluated using the Ames test (Salmonella typhimurium TA98 and TA100 strains), and no increase in revertant colony formation was observed at concentrations of 1–5 mg/plate. TS exhibited DNA protective activity in a pBR322 plasmid DNA model against UV- and H₂O₂-induced damage, indicating antioxidant-like properties that mitigated oxidative stress. Molecular docking simulations revealed moderate binding affinity of TS with DNA polymerase delta (−5.7 kcal/mol), Topoisomerase 1 (−5.9 kcal/mol), Glutamate dehydrogenase (−5.4 kcal/mol), and Glutamine synthetase (−6.1 kcal/mol). These findings indicate that TS does not pose cytotoxic, genotoxic or mutagenic risks at all application times and concentrations, while its DNA-protective role may counteract oxidative damage. Supported by a comprehensive array of test batteries, this study demonstrates that the current use of TS exhibits a reliable safety profile. Furthermore, it underscores that its protective effects against DNA-damaging agents warrant careful consideration rather than being overlooked.