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Untreated hexamethylenetetramine (HMT) was discharged into the Tone River in the central area of Japan, and the risk management plan in the watershed area has been strengthened because HMT is the precursor of formaldehyde (FA) regulated by Japanese water supply law. The release of HMT could occur not only in steady but also in unsteady environmental conditions. In this context, no quantitative environmental risk assessments have dealt with the combined events of FA precursor outflow and natural disasters, such as a massive tsunami attack. In this study, we estimated the time course changes of HMT concentrations at the near water treatment plant (WTP) intakes due to tsunami run-up in the river after HMT discharge from facilities along the river during a massive tsunami attack, then potential ecological and health impacts were estimated. This method has a strong analytical ability to reveal the relationship between wave source and inland water run-up in consideration of 3D density flow. For ecological risk, the half maximal effective concentration (EC50) was employed. We found that HMT concentration would not reach a level of concern even after the accident. For potential health risk in terms of the possible maximum inlet concentration of HMT at the WTP, the FA formation amount was 5.3 × 10−2 mg/L, which was below the water quality standard. [ABSTRACT FROM AUTHOR]