US EPA

5467423 

Technical Report 

Incorporation of in vitro metabolism data in a physiologically based pharmacokinetic (PBPK) model for chloroprene 

Ramboll :: Ramboll 

2020 

English 

is related to other part(s) 9959766 Follow up – External peer review of a report on physiologically based pharmacokinetic (PBPK) modeling for chloroprene and a supplemental analysis of metabolite clearance

A physiologically based pharmacokinetic (PBPK) model for chloroprene in the mouse, rat and
human has been developed that relies solely on in vitro studies for the estimation of model
parameters describing tissue metabolism and partitioning. The PBPK model accurately predicts in
vivo pharmacokinetic data from a 6-hr, nose-only chloroprene inhalation study conducted with
female B6C3F1 mice, the most sensitive species/gender for lung tumors in the 2-year bioassays
conducted with chloroprene. This PBPK model has been developed to support an inhalation
cancer risk assessment for chloroprene using in vitro data on the metabolism of chloroprene to
reactive epoxides in the lung target tissue of mice and humans. The approach for calculating
target tissue (lung) dose metrics was based on the PBPK modeling performed in support of the
inhalation cancer risk assessment for methylene chloride and represents the best available
science for determining the impact of species differences in metabolism of chloroprene.