Methadone Contributes to N‑Nitrosodimethylamine Formation in Surface Waters and Wastewaters during Chloramination

N-Nitrosodimethylamine (NDMA) is a probable human carcinogen that forms in drinking water as a disinfection byproduct. Several specific precursor chemicals present during chloramination are known but cannot account for the total observed NDMA formation potential (FP) in drinking waters. We discovered a pharmaceutical precursor of NDMA with high FP using a liquid chromatography/quadrupole/time-of-flight mass spectrometry (LC/QTOF-MS) screening procedure. The pharmaceutical methadone, which is used to mitigate heroin withdrawal symptoms and is also prescribed for chronic pain, contains a dimethylisopropylamine functional group that reacts to form large amounts of NDMA upon chloramination. In this study, methadone had a molar NDMA yield ranging from 23 to 70% depending on chloramine dose (1–150 mg of Cl₂/L) and was responsible for between 1 and 10% of NDMA FP in most raw surface waters in which it was detected and up to 62% of NDMA FP in wastewater. Samples with higher methadone concentrations had greater NDMA FP. We measured a median methadone concentration of 23 ng/L with a range of 1–2256 ng/L among detections, which was consistent with high occurrence rates and environmental persistence for methadone in the published literature for surface waters and wastewaters. A literature review of methadone use, metabolism, and fate in the United States resulted in a prediction of low nanogram per liter levels of methadone-associated NDMA FP at drinking water treatment plants (DWTPs) downstream of communities using methadone. Medicinal use of methadone potentially displaces and transforms the health risks associated with heroin use by individuals to possible cancer risk for populations served by downstream DWTPs. This work is among the first to contrast known public health benefits of pharmaceutical-taking patients against the potential exposure of millions of people to physiologically relevant levels of carcinogenic NDMA in chloraminated drinking water.