Scientific Basis of Tolerable Daily Intake Derivation in Japan: Analysis of Study Types, Uncertainty Factors, and Critical Effect Levels in FSCJ Risk Assessment Reports.

This study aimed to clarify the scientific basis for deriving Tolerable Daily Intake (TDI) values in risk assessments conducted by the Food Safety Commission of Japan (FSCJ), with a particular focus on the types of studies used, uncertainty factors (UFs), and critical effect levels (No-Observed-Adverse-Effect Levels and Lowest-Observed-Adverse-Effect Levels). We reviewed 77 chemical risk assessment reports published by the FSCJ as of October 2022. Using a standardized data extraction template developed with reference to the ATSDR and IRIS formats, ten trained reviewers examined and coded relevant toxicological information. In total, 46 reports were included in the final analysis. Most TDI values (73.9%) were derived from animal studies and were typically accompanied by large UFs ranging from 100 to 1000. Human-based TDIs derived from human observational (15.2%) and human intervention (10.9%) studies accounted for a smaller proportion but were generally associated with higher TDI values and smaller UFs. The examination of the NOAEL and LOAEL distributions indicated that lower exposure thresholds were primarily based on human study, whereas higher thresholds predominantly relied on animal studies. The derivation of TDI in Japan relies predominantly on animal study. Enhancing the availability of high-quality human data and improving consistency in the application of UFs may strengthen the transparency and scientific validity of health-based guidance in the future.