title: Application of Biologically Based Lumping To Investigate the Toxicokinetic Interactions of a Complex Gasoline Mixture.
abstract: People are often exposed to complex mixtures of environmental chemicals such as gasoline, tobacco smoke, water contaminants, or food additives. We developed an approach that applies chemical lumping methods to complex mixtures, in this case gasoline, based on biologically relevant parameters used in physiologically based pharmacokinetic (PBPK) modeling. Inhalation exposures were performed with rats to evaluate the performance of our PBPK model and chemical lumping method. There were 109 chemicals identified and quantified in the vapor in the chamber. The time-course toxicokinetic profiles of 10 target chemicals were also determined from blood samples collected during and following the in vivo experiments. A general PBPK model was used to compare the experimental data to the simulated values of blood concentration for 10 target chemicals with various numbers of lumps, iteratively increasing from 0 to 99. Large reductions in simulation error were gained by incorporating enzymatic chemical interactions, in comparison to simulating the individual chemicals separately. The error was further reduced by lumping the 99 nontarget chemicals. The same biologically based lumping approach can be used to simplify any complex mixture with tens, hundreds, or thousands of constituents.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Micah N
authors.initials: MN
authors.lastname: Jasper
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Sheppard A
authors.initials: SA
authors.lastname: Martin
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Oshiro
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Jermaine
authors.initials: J
authors.lastname: Ford
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bushnell
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Hisham
authors.initials: H
authors.lastname: El-Masri
mesh_terms: D000818:Animals; D045424:Complex Mixtures / Q000633:toxicity; D005260:Female; D005742:Gasoline / Q000633:toxicity*; D019570:Inhalation Exposure; D008962:Models, Theoretical; D020318:Rats, Long-Evans; D066007:Toxicokinetics
chemical_list: D045424:Complex Mixtures; D005742:Gasoline