Criterion of molecular size to evaluate the bioaccumulation potential of chemicals in fish

To evaluate the bioaccumulation potential of chemicals in fish, a molecular-size descriptor, D(max aver), has been used as a weight of evidence under the EU REACH. The D(max aver) value, however, is estimated on the basis of 3-D structures of possible stable conformers in a vacuum using OASIS software that requires expertise upon parameter input. We developed a method to calculate the 3-D conformers in water, which is more suitable for bioaccumulation potential evaluation in an aquatic environment, by introducing MD simulation. By examining the relationship of the calculated molecular size of 1665 chemicals with their reported BCF values, we found that 17.1 Å of D(max aver) or 15.6 Å of D(max min) was a threshold of molecular size in water to predict the low bioaccumulation (i.e., BCF<5000) of a chemical. Setting this threshold as a new standard would reduce the number of animal tests without compromising the quality of safety evaluation.