Statistical Post-Processing Method for Evaluating Bioaccumulation in Fish Due to Dietary Exposure in Japan

Abstract

In 2018, the dietary exposure bioaccumulation fish test of the Organization for Economic Co-operation and Development Test Guideline No. 305 was introduced into Japan’s Chemical Substances Control Law. The Japanese government has adopted a single definitive testing criterion for the absence of high bioaccumulation: the growth-corrected kinetic dietary magnification factor (BMF_Kg) must be less than 0.007. The aim of this study was to decrease regulatory restrictions in order to increase newly developed chemical substances and their subsequent approval of their manufacture and import, i.e., the present study was motivated by concerns over the criterion being too restrictive, rather than scientific concerns, such as uncertainty in criterion. We used statistical post-processing to assess the possibility of expanding the criteria for not being highly bioaccumulative. Based on our results, we proposed the criterion that the test substance should be considered not highly bioaccumulative if the following two conditions are met: (1) The ratio of the maximum to the minimum measured 5% lipid-standardized biomagnification factor at the end of the uptake phase (BMF_5%, n = 5) for the test substance and reference substance should be less than 3.0, and (2) For the measured BMF_5% of the test substance (n = 5), the probability that the next (the sixth) BMF_5% is below 0.0334 should exceed 95% based on statistical post-processing. It is worth noting that the BMF_5% values should only be applied for non-ionizable lipid soluble compounds. Application of our suggested approach to Japan implies that the criterion for chemical substances that are not highly bioaccumulative in the dietary exposure bioaccumulation fish test would be increased from 0.007 to 0.0149.