Chemical persistency studies are crucial for the regulatory risk assessment of chemicals. One of their major challenges is the formation of so-called non-extractable residues (NERs) in soil as current analytics cannot easily differentiate hazardous xenobiotic NERs from harmless biogenic NERs (bioNERs). Widely-used radiocarbon (14C) tracing allows a rapid quantitation of total NERs whereas stable isotope labeling (13C or 15N) can track bioNERs but is not economically efficient. This study investigated the potential of deuterium isotope probing (DIP) as a new method to simplify the risk assessment associated with xenobiotic NER (xenoNER) formation. Deuterium (D) and 13C tracers were used to study the simulated degradation of three model compounds in soil, the results of which showed negligible incorporation of D into bioNERs as compared to 13C. This indicates the high potential of DIP for a rapid estimation of the hazardous xenoNERs, which could simplify chemical persistency studies in soil.