Application of manure, biosolids, and recycled wastewater to croplands could be a potential pathway through which trace organic compounds (TOrCs) may be taken up by food crops. We present a framework to prepare a short list of TOrCs for detailed risk assessment and evaluation in terms of bioaccumulation. The framework was modified from Lipinski's method to predict drug permeability based on four critical properties: (i) molecular weight (MW); (ii) lipophilicity (expressed as log, the octanol-water partition coefficient); (iii) H-bond acceptors; and (iv) H-bond donors. The literature shows that the compounds with MW ranging from 200 to 500 can readily diffuse through mammalian membranes, the uptake of compounds with log >5 is hindered, and an excessive number of H-bond donors and H-bond acceptors reduces the permeability across a mammalian membrane bilayer. In general, mammalian and plant membranes are similar in structure and functions. Based on these four properties, we developed the "Rule of 3," which states that greater absorption and higher permeability of a TOrC is likely when its log is <3, its MW is <300, H-bond donors are <3, and H-bond acceptors are <6. Applicability of the framework was tested with published data, which showed that uptake and bioaccumulation of TOrCs in plants decreased in the order: Rule of 3 > Rule of 3 to 5 (log between 3 and 5, MW between 300 and 500, H-bond acceptors between 3 and 6, and H-bond donors between 3 and 5) > Rule of 5 (log >5, MW >500, H-bond acceptors >10, and H-bond donors <5). We conclude that TOrCs following the "Rule of 3" could be prioritized for detailed risk assessment involving dietary exposure.