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This study describes the development and intercomparison of generic physiologically-based toxicokinetic (PBTK) models for humans comprised of internally consistent one-compartment (1Co-) and multi-compartment (MCo-) implementations (G-PBTK). The G-PBTK models were parameterized for an adult male (70 kg) using common physiological parameters and in vitro biotransformation rate estimates and subsequently evaluated using independent concentration versus time data (n = 6) and total elimination half-lives (n = 15) for diverse organic chemicals