A XXXX risk assessment using a Monte Carlo analysis of parameter uncertainty in conjunction with physiologically-based pharmacokinetic modeling.

@entity1 @entity4966 @entity19 @entity5 @entity2974 @entity2804 @entity4965
A Monte Carlo simulation is incorporated into a risk assessment for @entity4965 ( @entity4966 ) using physiologically-based pharmacokinetic (PBPK) modeling coupled with the linearized multistage model to derive @entity1 carcinogenic risk extrapolations. The Monte Carlo technique incorporates physiological parameter variability to produce a statistically derived range of risk estimates which quantifies specific uncertainties associated with PBPK risk assessment approaches. Both inhalation and ingestion exposure routes are addressed. Simulated exposure scenarios were consistent with those used by the Environmental Protection Agency (EPA) in their @entity4966 risk assessment. Mean values of physiological parameters were gathered from the literature for both @entity19 (carcinogenic bioassay subjects) and for @entity1 . Realistic physiological value distributions were assumed using existing data on variability. @entity19 @entity5 bioassay data were correlated to total @entity4966 metabolized and area-under-the-curve (blood concentration) @entity2804 ( @entity2974 ) as determined by a @entity19 PBPK model. These internal dose metrics were used in a linearized multistage model analysis to determine dose metric values corresponding to 10(-6) lifetime excess @entity5 risk. Using a @entity1 PBPK model, these metabolized doses were then extrapolated to equivalent @entity1 exposures (inhalation and ingestion). The Monte Carlo iterations with varying @entity19 and @entity1 physiological parameters produced a range of @entity1 exposure concentrations producing a 10(-6) risk.
