A clinically useful all-in-one endodontic irrigant with combined proteolytic and decalcifying properties is still elusive. In this study, the chemical effects of dissolving the tetrasodium salts of 1-hydroxyethane 1,1-diphosphonic acid (Na4HEDP) or Na4EDTA directly in sodium hypochlorite (NaOCl) irrigants in polypropylene syringes were assessed during the course of 1 hour.The solubility of the salts in water was determined. Their compatibility with 1% and 5% NaOCl was measured by iodometric titration and in a calcium complexation experiment by using a Ca2+-selective electrode.The salts dissolved within 1 minute. The dissolution maximum of Na4HEDP in water (wt/total wt) was 44.6% ± 1.6%. The corresponding dissolution maximum of Na4EDTA was 38.2% ± 0.8%. Na4HEDP at 18% in 5% NaOCl caused a mere loss of 16% of the initially available chlorine during 1 hour. In contrast, a corresponding mixture between NaOCl and the Na4EDTA salt caused 95% reduction in available chlorine after 1 minute. Mixtures of 3% Na4EDTA with 1% NaOCl were more stable, but only for 30 minutes. Na4HEDP lost 24% of its calcium complexation capacity after 60 minutes. The corresponding loss for Na4EDTA was 34%.The compatibility and solubility of particulate Na4HEDP with/in NaOCl solutions are such that these components can be mixed and used for up to 1 hour. In contrast, short-term compatibility of the Na4EDTA salt with NaOCl solutions was considerably lower, decreasing at higher concentrations of either compound. Especially for Na4HEDP but also for Na4EDTA, the NaOCl had little effect on calcium complexation.