<?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%">Gaither, Kari A</style></author><author><style face="normal" font="default" size="100%">Tyrrell, Kimberly</style></author><author><style face="normal" font="default" size="100%">Garcia, Whitney</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Smith, Jordan N</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Human in vitro metabolism of an environmental mixture of polycyclic aromatic hydrocarbons (PAH) found at the Portland Harbor Superfund Site.</style></title><secondary-title><style face="normal" font="default" size="100%">Toxicol Lett</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Toxicol Lett</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Chromatography, High Pressure Liquid</style></keyword><keyword><style  face="normal" font="default" size="100%">Environmental Pollutants</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">Microsomes, Liver</style></keyword><keyword><style  face="normal" font="default" size="100%">Polycyclic Aromatic Hydrocarbons</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2025</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2025 Oct</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">412</style></volume><pages><style face="normal" font="default" size="100%">172-181</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 widespread environmental contaminants that pose health risks to humans. Toxicity testing approaches of PAHs have evolved from traditional rodent models to New Approach Methodologies (NAMs), such as high-throughput screening in zebrafish, enabling rapid evaluation of chemical hazards. However, translating toxicity findings from laboratory systems to humans remains difficult due to complexity and species-specific differences. Chemical dosimetry modeling offers a quantitative framework to bridge this gap, but its accuracy depends on robust knowledge of PAH metabolism. The objective of this study was to measure human metabolism rates of Supermix-10, the ten most abundant PAHs found at the Portland Harbor Superfund Site, to support development of human pharmacokinetic models. We incubated individual PAHs from Supermix-10 in pooled human liver microsomes and quantified parent PAH disappearance using high-performance liquid chromatography (HPLC) with UV and florescent detection. To assess the potential of mixture interactions, we also measured metabolism of all 10 compounds in an equimolar mixture and compared rates of parent disappearance to those observed for individual PAHs. All Supermix-10 PAHs demonstrated rapid parent compound disappearance in human hepatic microsomes. PAHs grouped into three metabolism patterns: high metabolism rates and capacity (2-methylnaphthalene, acenaphthylene, fluorene, naphthalene), high affinity metabolism that rapidly achieves low-level saturation (benzo[a]anthracene, chrysene), and moderate metabolism rates and capacity (fluoranthene, pyrene, retene, phenanthrene). Smaller PAHs exhibited faster metabolism, and higher metabolism rates correlated inversely with molecular weight. When incubated in an equimolar mixture, Supermix-10 demonstrated significantly slower metabolism (47-89 %) compared to metabolism of individual PAHs at the same concentration. These findings enhance our understanding of PAH metabolism in humans and demonstrate significant mixture interactions under the conditions tested. Our findings offer insights into the metabolic behavior of Supermix-10 and provide critical metabolism rate data to support the development of physiological based pharmacokinetic (PBPK) models. Dosimetry models can translate PAH chemical dosimetry from high-throughput testing platforms, like zebrafish and cellular system assays, to human exposures enhancing the accuracy and reliability of PAH risk assessments.&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%">Rude, Christian I</style></author><author><style face="normal" font="default" size="100%">Smith, Jordan N</style></author><author><style face="normal" font="default" size="100%">Scott, Ricky P</style></author><author><style face="normal" font="default" size="100%">Schultz, Katherine J</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Tanguay, Robyn L</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">A mixture parameterized biologically based dosimetry model to predict body burdens of polycyclic aromatic hydrocarbons in developmental zebrafish toxicity assays.</style></title><secondary-title><style face="normal" font="default" size="100%">Toxicol Sci</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Toxicol Sci</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Body Burden</style></keyword><keyword><style  face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword><keyword><style  face="normal" font="default" size="100%">Embryo, Nonmammalian</style></keyword><keyword><style  face="normal" font="default" size="100%">Models, Biological</style></keyword><keyword><style  face="normal" font="default" size="100%">Polycyclic Aromatic Hydrocarbons</style></keyword><keyword><style  face="normal" font="default" size="100%">Toxicity Tests</style></keyword><keyword><style  face="normal" font="default" size="100%">Toxicokinetics</style></keyword><keyword><style  face="normal" font="default" size="100%">Water Pollutants, Chemical</style></keyword><keyword><style  face="normal" font="default" size="100%">Zebrafish</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2025</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2025 Jun 01</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">205</style></volume><pages><style face="normal" font="default" size="100%">326-343</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 a group of environmental toxicants found ubiquitously as complex mixtures in human-impacted environments. Developmental zebrafish exposures have been used widely to study PAH toxicity, but most studies report nominal exposure concentrations. Nominal exposure concentrations can be unreliable dose metrics due to differences in toxicant bioavailability resulting from disparate exposure methodologies and chemical properties. Toxicokinetic modeling can predict toxicant tissue doses to facilitate comparison between exposures of different chemicals, methodologies, and biological models. We parameterize a biologically based dosimetry model for developmental zebrafish toxicity assays for 9 PAHs. The model was optimized with measurements from media, tissue, and plastic plate walls throughout a static developmental exposure to a mixture of 10 PAHs of high abundance within the Portland Harbor Superfund Site. Plate binding, volatilization, zebrafish permeability, and tissue-media partitioning coefficients vary widely between PAHs. Model predictions accounted for 83% and 54% of 48 hpf body burdens within a factor of 2 resulting from exposures to mixtures and individual PAHs, respectively. Accounting for solubility significantly improves model performance. Competition for active sites in metabolizing enzymes may change biotransformation kinetics between individual PAH and mixture exposures. Area under the curve estimations of concentrations in zebrafish resulted in altered hazard rankings from nominal exposure concentrations. Future work will be oriented to generalizing the model to other PAHs. This PAH dosimetry model improves the interpretability of developmental zebrafish toxicity assays by providing time-resolved body burdens from nominal exposure concentrations.&lt;/p&gt;
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