From a theoretical framework of human exposure and dose assessment to computational system implementation: The Modeling ENvironment for TOtal Risk studies (MENTOR)

Georgopoulos and Lioy ( 1994) presented a theoretical framework for exposure analysis, incorporating multiple levels of empirical and mechanistic information while characterizing/ reducing uncertainties. The present review summarizes efforts towards implementing that framework, through the development of a mechanistic source-to- dose Modeling ENvironment for TOtal Risks studies ( MENTOR), a computational toolbox that provides various modeling and data analysis tools to facilitate assessment of cumulative and aggregate ( multipathway) exposures to contaminant mixtures. MENTOR adopts a Person Oriented Modeling ( POM) approach that can be applied to either specific individuals or to populations/ subpopulations of interest; the latter is accomplished by defining samples of virtual individuals that statistically reproduce the physiological, demographic, etc., attributes of the populations studied. MENTOR implementations currently incorporate and expand USEPA's SHEDS ( Stochastic Human Exposure and Dose Simulation) approach and consider multiple exposure routes ( inhalation, food, drinking water intake; non- dietary ingestion; dermal absorption). Typically, simulations involve: ( 1) characterizing background levels of contaminants by combining model predictions and measurement studies; ( 2) characterizing multimedia levels and temporal profiles of contaminants in various residential and occupational microenvironments; ( 3) selecting sample populations that statistically reproduce essential demographics ( age, gender, race, occupation, education) of relevant population units ( e. g., census tracts); ( 4) developing activity event sequences for each member of the sample by matching attributes to entries of USEPA's Consolidated Human Activity Database ( CHAD); ( 5) calculating intake rates for the sample population members, reflecting physiological attributes and activities pursued; ( 6) combining intake rates from multiple routes to assess exposures; (7) estimating target tissue doses with physiologically based dosimetry/toxicokinetic modelling.