Relatively few measured data are available for the thousands of chemicals requiring hazard and risk assessment. The whole body, total elimination half-life (HL_T) and the whole body, primary biotransformation half-life (HL_B) are key parameters determining the extent of bioaccumulation, biological concentration, and risk from chemical exposure. A one-compartment pharmacokinetic (1-CoPK) mass balance model was developed to estimate organic chemical HL_B from measured HL_T data in mammals. Approximately 1900 HLs for human adults were collected and reviewed and the 1-CoPK model was parametrized for an adult human to calculate HL_B from HL_T. Measured renal clearance and whole body total clearance data for 306 chemicals were used to calculate empirical HL_B,emp. The HL_B,emp values and other measured data were used to corroborate the 1-CoPK HL_B model calculations. HLs span approximately 7.5 orders of magnitude from 0.05 h for nitroglycerin to 2 × 10⁶ h for 2,3,4,5,2′,3′,5′,6′-octachlorobiphenyl with a median of 7.6 h. The automated Iterative Fragment Selection (IFS) method was applied to develop and evaluate various quantitative structure–activity relationships (QSARs) to predict HL_T and HL_B from chemical structure and two novel QSARs are detailed. The HL_T and HL_B QSARs show similar statistical performance; that is, r² = 0.89, r^2-ext = 0.72 and 0.73 for training and external validation sets, respectively, and root-mean-square errors for the validation data sets are 0.70 and 0.75, respectively.