Molecular size cutoff criteria for screening bioaccumulation potential: fact or fiction?

It has been asserted that, when screening chemicals for bioaccumulation potential, molecular size cutoff criteria (or indicators) can be applied above which no, or limited, bioaccumulation is expected. The suggested molecular size values have increased over time as more measurements have become available. Most of the proposed criteria have been derived from unevaluated fish bioconcentration factor (BCF) data, and less than 5% of existing organic substances have measured BCFs.We critically review the proposed criteria, first by considering other factors that may also contribute to reduced bioaccumulation for larger molecules, namely, reduced bioavailability in the water column, reduced rate of uptake corresponding to reduced diffusion rates, and the effects of biotransformation and growth dilution. An evaluated BCF and bioaccumulation factor (BAF) database for more than 700 substances and dietary uptake efficiency data are compared against proposed cutoff values. We examine errors associated with interpreting BCF data, particularly for developing molecular size criteria of bioaccumulation potential. Reduced bioaccumulation that is often associated with larger molecular size can be explained by factors other than molecular size, and there is evidence of absorption of molecules exceeding the proposed cutoff criteria. The available data do not support strict cutoff criteria, indicating that the proposed values are incorrect. Rather than assessing bioaccumulation using specific chemical properties in isolation, holistic methods that account for competing rates of uptake and elimination in an organism are recommended. An integrated testing strategy is suggested to improve knowledge of the absorption and bioaccumulation of large substances.