In Vitro Cytotoxicity of Cyanuric Acid and Selected Derivatives

Abstract

Background Cyanuric acid and its derivatives belong to the group of s-triazines. They have wide industrial application, generally in the production of pesticides, bleaching agents and disinfectants. Recent reports showed significant negative effect of cyanuric acid in combination with melamine but low general cytotoxicity of cyanuric acid alone. However, evaluations of cyanuric acid toxicity against different human cell types using a panel of in vitro assays have not been performed. In addition, little is known about the cytotoxicity and potential antitumor effects of certain cyanuric acid derivatives, for example trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate. Aim To investigate the toxicity of cyanuric acid, trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate using different cancer cell lines and normal fibroblasts. Materials and Methods MTT, Neutral red and clonogenic assays were used to characterize the in vitro cytotoxicity of cyanuric acid, trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate. Different concentrations of the compounds were tested on three cancer cell lines (HeLa, A549, CaOV) and normal human fibroblasts. IC 50 values were calculated and compared. Intracellular ATP measurements and microscopic evaluations of cellular morphology after exposure to cyanuric acid, trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate were performed. Results Among the three test-agents trichloroisocyanuric acid (TCIC) demonstrated the highest cytotoxicity in vitro. Interestingly, MTT assays indicated that the toxic effects of TCIC were mainly directed towards cancer cells affecting mitochondrial functionality. Clonogenicity of cancer cell lines was completely inhibited in the presence of low concentrations of the triazine. Exposition to TCIC influenced the morphology and intracellular ATP concentration in both cancer cells and normal fibroblasts but the observed effects were stronger in cancer cells. Conclusion The order of cytotoxicity of the tested compounds is as follows: trichloroisocyanuric acid>cyanuric acid>1,3,5-tris(2-hydroxyethyl) isocyanurate. Trichloroisocyanuric acid demonstrates selective antitumor effect.

Exceptional Nuclease Resistance of DNA and RNA with the Addition of Small-Molecule Nucleobase Mimics

“…We observe the use of CA at low toxicity in vitro, corroborating previous studies . For CA–R, the improvements in DNA lifetimes result in higher toxicity.…”

“…We observe the use of CA at low toxicity in vitro, corroborating previous studies. 27 For CA−R, the improvements in DNA lifetimes result in higher toxicity. With further investigations, it is possible that the bundling and protective ability could be disentangled from the damage to cells, for example, by replacing the C6 chain with an ethylene glycol chain.…”

The Drinking Water and Swimming Pool Disinfectant Trichloroisocyanuric Acid Causes Chlorination Stress Enhancing Solar UV‐Induced Inflammatory Gene Expression in AP‐1 Transgenic SKH‐1 Luciferase Reporter Mouse Skin†

“…Chlorinated isocyanuric acid derivatives (including the chloramines trichloroisocyanuric acid [TCIC; CAS#: 87‐90‐1], dichloroisocyanuric acid [DCIC] and isocyanuric acid chlorinated in situ in the presence of HOCl) are used worldwide as alternate chlorination agents serving as HOCl precursor and stabilizer compounds that ensure sustained release in aqueous environments such as drinking water reservoirs and swimming pools used according to EPA‐recommended hazard assessment and concentration levels (≤300 μM) (23–26). Ubiquitous use of these agents is predicated on various seemingly favorable chemical features including synthetic accessibility, shelf life, established safety profile and photostability, a property of special significance in the context of pool disinfection where the well‐established UV instability of HOCl/OCl − compromises sustained maintenance of antimicrobial chlorination levels (23–28). Remarkably, biological effects of TCIC on epithelial human tissues are largely understudied, and most available evidence has been obtained performing standard regulatory toxicity assessment (including acute irritant exposure and long‐term feeding models).…”

“…dichloroisocyanuric acid [DCIC] and isocyanuric acid chlorinated in situ in the presence of HOCl) are used worldwide as alternate chlorination agents serving as HOCl precursor and stabilizer compounds that ensure sustained release in aqueous environments such as drinking water reservoirs and swimming pools used according to EPA-recommended hazard assessment and concentration levels (≤300 lM) (23)(24)(25)(26). Ubiquitous use of these agents is predicated on various seemingly favorable chemical features including synthetic accessibility, shelf life, established safety profile and photostability, a property of special significance in the context of pool disinfection where the wellestablished UV instability of HOCl/OCl À compromises sustained maintenance of antimicrobial chlorination levels (23)(24)(25)(26)(27)(28). Remarkably, biological effects of TCIC on epithelial human tissues are largely understudied, and most available evidence has been obtained performing standard regulatory toxicity assessment (including acute irritant exposure and long-term feeding models).…”