Determining safety thresholds involves a combination of laboratory experiments, animal studies, and epidemiological research. Scientists identify the dose-response relationship of a substance, which helps establish the No-Observed-Adverse-Effect Level (NOAEL) and the Lowest-Observed-Adverse-Effect Level (LOAEL). These levels are then adjusted for uncertainty factors to account for variations in sensitivity among the human population, resulting in the Reference Dose (RfD) or Tolerable Daily Intake (TDI).
