<?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%">Morshead, Mackenzie L</style></author><author><style face="normal" font="default" size="100%">Truong, Lisa</style></author><author><style face="normal" font="default" size="100%">Carrell, Steven J</style></author><author><style face="normal" font="default" size="100%">Scott, Richard</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%">Chemical structure drives developmental toxicity of alkyl-substituted naphthalenes in zebrafish.</style></title><secondary-title><style face="normal" font="default" size="100%">Environ Int</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Environ Int</style></alt-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Animals</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular Docking Simulation</style></keyword><keyword><style  face="normal" font="default" size="100%">Naphthalenes</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%">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 Oct</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">204</style></volume><pages><style face="normal" font="default" size="100%">109837</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Naphthalene and its alkyl-substituted derivatives are among the most abundant polycyclic aromatic hydrocarbons (PAHs) in environmental and human exposure studies, yet their developmental toxicity and mode of action remain poorly understood due to challenges in testing semi-volatile compounds. This study developed a vial based, high throughput method to effectively assess the activity of naphthalenes and a set of 24 alkyl-substituted naphthalenes. Early life stage zebrafish were exposed to a concentration series of each chemical (0-50&amp;nbsp;µM) in rotating sealed glass vials to minimize volatilization. Benchmark concentration (BMC) values were calculated for morphological endpoints and lowest effect levels were determined for behavioral effects. The data were assessed for evidence of a narcotic mode of action using body burden measurements for select chemicals and logK modeling. Targeted transcriptomics at a single concentration and timepoint as well as in silico molecular docking were conducted to generate mode of action hypotheses. The vial method enabled detection of highly variable developmental toxicity not previously observed using standard 96-well plate exposures. LogK and body burden were poor predictors of toxicity, suggesting a non-narcotic mode of action. Transcriptomic analysis revealed evidence for the disruption of glucocorticoid signaling pathways. Molecular docking identified potential protein targets (e.g., CYP1A2, NT5E, FOLR1) that may mediate observed effects. This study demonstrates the importance of appropriate exposure methods for semi-volatile compounds, reveals structure-dependent toxicity among alkyl-substituted naphthalenes, and provides a foundation for further mechanistic studies and improved risk assessment of alkyl-substituted PAHs.&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%">Morshead, Mackenzie L</style></author><author><style face="normal" font="default" size="100%">Truong, Lisa</style></author><author><style face="normal" font="default" size="100%">Simonich, Michael T</style></author><author><style face="normal" font="default" size="100%">Moran, Jessica E</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%">Developmental toxicity of alkylated PAHs and substituted phenanthrenes: Structural nuances drive diverse toxicity and AHR activation.</style></title><secondary-title><style face="normal" font="default" size="100%">Chemosphere</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Chemosphere</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2024</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2024 Dec 10</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">370</style></volume><pages><style face="normal" font="default" size="100%">143894</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 diverse class of chemicals that occur in complex mixtures including parent and substituted PAHs. To understand the hazard posed by complex environmental PAH mixtures, we must first understand the structural drivers of activity and mode of action of individual PAHs. Understanding the toxicity of alkylated PAHs is important as they often occur in higher abundance in environmental matrices and can be more biologically active than their parent compounds. 104 alkylated PAHs were screened from 11 different parent compounds with emphasis on substituted phenanthrenes and their structurally dependent toxicity differences. Using a high-throughput early life stage zebrafish assay, embryos were exposed to concentrations between 0.1 and 100&amp;nbsp;μM and assessed for morphological and behavioral outcomes. The aryl hydrocarbon receptor (AHR) is often implicated in the toxicity of PAHs and the induction of cytochrome P4501A (cyp1a) is an excellent biomarker of Ahr activation. Embryos were evaluated for cyp1a induction using a fluorescence reporter line. Alkyl and polar phenanthrene derivatives were further assessed for spatial cyp1a expression and Ahr dependence of morphological effects. In the alkyl PAH screen 35 (33.7%) elicited a morphological or behavioral response and of those 23 (65%) also induced cyp1a. 31 (29.8%) of the chemicals only induced cyp1a. Toxicity varied substantially in response to substitution location, the amount of ring substitutions and alkyl chain length. Cyp1a induction varied by parent compound group and was a poor indicator of morphological or behavioral outcomes. Polar phenanthrenes were more biologically active than alkylated phenanthrene derivatives and their toxicity was not dependent upon the Ahr2, Ahr1a or Ahr1b when tested individually, despite cyp1a induction by 50% of polar phenanthrenes. Our results demonstrated that induction of cyp1a did not always correlate with PAH toxicity or Ahr dependence and that the type and location of phenanthrene substitution determined potency.&lt;/p&gt;
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