Cell objects occupy most of Endothelial Cell (99%) and Hepatocyte (90%) spaces. (D) Each Sinusoid Segment configures a parsimony-guided multilevel variety of components so that during execution it functions as an analog of sinusoid components and features averaged across many lobules Sinusoid Segment dimensions are Monte Carlo determined to mimic hepatic variability. Periportal (PP) to CV gradients provided intra-Lobular location information to each Hepatocyte. Bile (dotted green) flows separately from blood (solid red) but is not a factor for the hypotheses tested herein. All flow paths follow the directed graph. The Lobular configurations used herein were validated earlier they are the result of cycling many times through the Iterative Refinement Protocol (described later) and successfully achieving several quantitative Target Attributes having stringent Similarity Criteria. (C) A Lobule comprises a directed graph with a concrete Sinusoid Segment (SS) object (a software agent) at each graph node. (B) A Liver comprises Monte Carlo-determined Lobule variants.

During execution, each discrete time step maps to 1 second.

Mouse Analog components and their organization (A) Mouse Analog comprises a Liver, Mouse Body, as well as a space to contain dose the space enables simulating intravenous, intraperitoneal, and intragastric dosing. Competing Mechanistic Hypotheses of Acetaminophen-Induced Hepatotoxicity Challenged by Virtual Experiments Fig 2

Spacecontrol mouse