<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Erin Madeen</style></author><author><style face="normal" font="default" size="100%">Siddens, Lisbeth K</style></author><author><style face="normal" font="default" size="100%">Sandra Uesugi</style></author><author><style face="normal" font="default" size="100%">McQuistan, Tammie</style></author><author><style face="normal" font="default" size="100%">Corley, Richard A</style></author><author><style face="normal" font="default" size="100%">Jordan Smith</style></author><author><style face="normal" font="default" size="100%">Katrina M Waters</style></author><author><style face="normal" font="default" size="100%">Susan C Tilton</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Ted J Ognibene</style></author><author><style face="normal" font="default" size="100%">Kenneth Turteltaub</style></author><author><style face="normal" font="default" size="100%">Williams, David E</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Toxicokinetics of benzo[a]pyrene in humans: Extensive metabolism as determined by UPLC-accelerator mass spectrometry following oral micro-dosing.</style></title><secondary-title><style face="normal" font="default" size="100%">Toxicol Appl Pharmacol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Toxicol. Appl. Pharmacol.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019 Feb 01</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">364</style></volume><pages><style face="normal" font="default" size="100%">97-105</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Benzo[a]pyrene (BaP), is a known human carcinogen (International Agency for Research on Cancer (IARC) class 1). The remarkable sensitivity (zepto-attomole C in biological samples) of accelerator mass spectrometry (AMS) makes possible, with de minimus risk, pharmacokinetic (PK) analysis following [C]-BaP micro-dosing of humans. A 46 ng (5 nCi) dose was given thrice to 5 volunteers with minimum 2 weeks between dosing and plasma collected over 72 h. [C]-BaP PK analysis gave plasma T and C values of 1.25 h and 29-82 fg/mL, respectively. PK parameters were assessed by non- compartment and compartment models. Intervals between dosing ranged from 20 to 420 days and had little impact on intra-individual variation. DNA, extracted from peripheral blood mononuclear cells (PBMCs) of 4 volunteers, showed measurable levels (LOD ~ 0.5 adducts/10 nucleotides) in two individuals 2-3 h post-dose, approximately three orders of magnitude lower than smokers or occupationally-exposed individuals. Little or no DNA binding was detectable at 48-72 h. In volunteers the allelic variants CYP1B1, or and GSTM1 or had no impact on [C]-BaP PK or DNA adduction with this very limited sample. Plasma metabolites over 72 h from two individuals (one CYP1B1 and one CYP1B1) were analyzed by UPLC-AMS. In both individuals, parent [C]-BaP was a minor constituent even at the earliest time points and metabolite profiles markedly distinct. AMS, coupled with UPLC, could be used in humans to enhance the accuracy of pharmacokinetics, toxicokinetics and risk assessment of environmental carcinogens.&lt;/p&gt;
</style></abstract></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">JG Teeguarden</style></author><author><style face="normal" font="default" size="100%">Tan, Yu-Mei</style></author><author><style face="normal" font="default" size="100%">Edwards, Stephen W</style></author><author><style face="normal" font="default" size="100%">Leonard, Jeremy A</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Corley, Richard A</style></author><author><style face="normal" font="default" size="100%">Molly Kile</style></author><author><style face="normal" font="default" size="100%">Staci M Simonich</style></author><author><style face="normal" font="default" size="100%">Stone, David</style></author><author><style face="normal" font="default" size="100%">Robyn L Tanguay</style></author><author><style face="normal" font="default" size="100%">Katrina M Waters</style></author><author><style face="normal" font="default" size="100%">Harper, Stacey L</style></author><author><style face="normal" font="default" size="100%">Williams, David E</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework.</style></title><secondary-title><style face="normal" font="default" size="100%">Environ Sci Technol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Environ. Sci. Technol.</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2016</style></year><pub-dates><date><style  face="normal" font="default" size="100%">05/2016</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">50</style></volume><pages><style face="normal" font="default" size="100%">4579-86</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Driven by major scientific advances in analytical methods, biomonitoring, computation, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the &quot;systems approaches&quot; used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences. Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more meaningful integration of exposure assessment and hazard identification. Together, the two frameworks form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">9</style></issue></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Crowell, Susan Ritger</style></author><author><style face="normal" font="default" size="100%">Amin, Shantu G</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Krishnegowda, Gowdahalli</style></author><author><style face="normal" font="default" size="100%">Sharma, Arun K</style></author><author><style face="normal" font="default" size="100%">Soelberg, Jolen J</style></author><author><style face="normal" font="default" size="100%">Williams, David E</style></author><author><style face="normal" font="default" size="100%">Corley, Richard A</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents.</style></title><secondary-title><style face="normal" font="default" size="100%">Toxicol Appl Pharmacol</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Toxicol. Appl. Pharmacol.</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Administration, Oral</style></keyword><keyword><style  face="normal" font="default" size="100%">Algorithms</style></keyword><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Benzo(a)pyrene</style></keyword><keyword><style  face="normal" font="default" size="100%">Benzopyrenes</style></keyword><keyword><style  face="normal" font="default" size="100%">Environmental Pollutants</style></keyword><keyword><style  face="normal" font="default" size="100%">Female</style></keyword><keyword><style  face="normal" font="default" size="100%">Injections, Intravenous</style></keyword><keyword><style  face="normal" font="default" size="100%">Mice</style></keyword><keyword><style  face="normal" font="default" size="100%">Models, Biological</style></keyword><keyword><style  face="normal" font="default" size="100%">Rats</style></keyword><keyword><style  face="normal" font="default" size="100%">Rats, Sprague-Dawley</style></keyword><keyword><style  face="normal" font="default" size="100%">Tissue Distribution</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2011</style></year><pub-dates><date><style  face="normal" font="default" size="100%">12/2011</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">257</style></volume><pages><style face="normal" font="default" size="100%">365-76</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated as byproducts of natural and anthropogenic combustion processes. Despite significant public health concern, physiologically based pharmacokinetic (PBPK) modeling efforts for PAHs have so far been limited to naphthalene, plus simpler PK models for pyrene, nitropyrene, and benzo[a]pyrene (B[a]P). The dearth of published models is due in part to the high lipophilicity, low volatility, and myriad metabolic pathways for PAHs, all of which present analytical and experimental challenges. Our research efforts have focused upon experimental approaches and initial development of PBPK models for the prototypic PAH, B[a]P, and the more potent, albeit less studied transplacental carcinogen, dibenzo[def,p]chrysene (DBC). For both compounds, model compartments included arterial and venous blood, flow limited lung, liver, richly perfused and poorly perfused tissues, diffusion limited fat, and a two compartment theoretical gut (for oral exposures). Hepatic and pulmonary metabolism was described for both compounds, as were fractional binding in blood and fecal clearance. Partition coefficients for parent PAH along with their diol and tetraol metabolites were estimated using published algorithms and verified experimentally for the hydroxylated metabolites. The preliminary PBPK models were able to describe many, but not all, of the available data sets, comprising multiple routes of exposure (oral, intravenous) and nominal doses spanning several orders of magnitude.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">3</style></issue><custom1><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/pubmed/22001385?dopt=Abstract</style></custom1></record></records></xml>