Use of spot urine sample results in physiologically based pharmacokinetic modeling of absorbed malathion doses in humans

Recently state health and regulatory agencies in California used a PB-PK model to estimate the absorbed doses of malathion in individuals allegedly exposed to aerial sprays during an urban pesticide application. Dose simulation in that study was performed on the results of single urine samples collected within 48 h of a potential exposure, and was based on a model validated with observed values from only a single volunteer. As a continuing effort another case study is presented in this chapter to validate the model with more human literature data. Results from this validation study showed that the time courses of the serial urinary malathion (metabolites) excretion presented in the literature were consistent with those simulated by the PB-PK model. When urine results collected from the literature cases at 8 - 12 h, 12 - 24 h, and 24 - 36 h or 24 - 48 h after initial exposure were postulated as spot samples, the majority (64/85) of the individual total absorbed doses simulated were within two-fold of their measured values, with no simulation doses exceeding three-fold. This validation study further showed that the accuracy would be improved considerably, if the simulation for each literature case were performed on two or more spot samples collected at different time points preferably within the first 24 or 36 h of exposure.