<?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%">Monica L. Vermillion Maier</style></author><author><style face="normal" font="default" size="100%">Siddens, Lisbeth K</style></author><author><style face="normal" font="default" size="100%">Jamie Pennington</style></author><author><style face="normal" font="default" size="100%">Sandra Uesugi</style></author><author><style face="normal" font="default" size="100%">Susan C Tilton</style></author><author><style face="normal" font="default" size="100%">Vertel, Emily A</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Lane G Tidwell</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%">Jordan Smith</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%">Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3&#039;-diindolylmethane (DIM) or Brussels sprouts.</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%">2023</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2023 Jan 12</style></date></pub-dates></dates><pages><style face="normal" font="default" size="100%">116377</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Utilizing the atto-zeptomole sensitivity of UPLC-accelerator mass spectrometry (UPLC-AMS), we previously demonstrated significant first-pass metabolism following escalating (25-250 ng) oral micro-dosing in humans of [C]-benzo[a]pyrene ([C]-BaP). The present study examines the potential for supplementation with Brussels sprouts (BS) or 3,3&#039;-diindolylmethane (DIM) to alter plasma levels of [C]-BaP and metabolites over a 48-h period following micro-dosing with 50 ng (5.4 nCi) [C]-BaP. Volunteers were dosed with [C]-BaP following fourteen days on a cruciferous vegetable restricted diet, or the same diet supplemented for seven days with 50 g of BS or 300 mg of BR-DIM® prior to dosing. BS or DIM reduced total [C] recovered from plasma by 56-67% relative to non-intervention. Dietary supplementation with DIM markedly increased T and reduced C for [C]-BaP indicative of slower absorption. Both dietary treatments significantly reduced C values of four downstream BaP metabolites, consistent with delaying BaP absorption. Dietary treatments also appeared to reduce the T and the plasma AUC() for Unknown Metabolite C, indicating some effect in accelerating clearance of this metabolite. Toxicokinetic constants for other metabolites followed the pattern for [C]-BaP (metabolite profiles remained relatively consistent) and non-compartmental analysis did not indicate other significant alterations. Significant amounts of metabolites in plasma were at the bay region of [C]-BaP irrespective of treatment. Although the number of subjects and large interindividual variation are limitations of this study, it represents the first human trial showing dietary intervention altering toxicokinetics of a defined dose of a known human carcinogen.&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%">Monica L. Vermillion Maier</style></author><author><style face="normal" font="default" size="100%">Siddens, Lisbeth K</style></author><author><style face="normal" font="default" size="100%">Jamie Pennington</style></author><author><style face="normal" font="default" size="100%">Sandra Uesugi</style></author><author><style face="normal" font="default" size="100%">Labut, Edwin M</style></author><author><style face="normal" font="default" size="100%">Vertel, Emily A</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Lane G Tidwell</style></author><author><style face="normal" font="default" size="100%">Susan C Tilton</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%">Jordan Smith</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%">Impact of phenanthrene co-administration on the toxicokinetics of benzo[a]pyrene in humans. UPLC-accelerator mass spectrometry following oral microdosing.</style></title><secondary-title><style face="normal" font="default" size="100%">Chem Biol Interact</style></secondary-title><alt-title><style face="normal" font="default" size="100%">Chem Biol Interact</style></alt-title></titles><dates><year><style  face="normal" font="default" size="100%">2023</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2023 Jun 25</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">382</style></volume><pages><style face="normal" font="default" size="100%">110608</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Current risk assessments for environmental carcinogens rely on animal studies utilizing doses orders of magnitude higher than actual human exposures. Epidemiological studies of people with high exposures (e.g., occupational) are of value, but rely on uncertain exposure data. In addition, exposures are typically not to a single chemical but to mixtures, such as polycyclic aromatic hydrocarbons (PAHs). The extremely high sensitivity of accelerator mass spectrometry (AMS) allows for dosing humans with known carcinogens with de minimus risk. In this study UPLC-AMS was used to assess the toxicokinetics of [C]-benzo[a]pyrene ([C]-BaP) when dosed alone or in a binary mixture with phenanthrene (Phe). Plasma was collected for 48&amp;nbsp;h following a dose of [C]-BaP (50&amp;nbsp;ng, 5.4&amp;nbsp;nCi) or the same dose of [C]-BaP plus Phe (1250&amp;nbsp;ng). Following the binary mixture, C of [C]-BaP significantly decreased (4.4-fold) whereas the volume of distribution (V) increased (2-fold). Further, the toxicokinetics of twelve [C]-BaP metabolites provided evidence of little change in the metabolite profile of [C]-BaP and the pattern was overall reduction consistent with reduced absorption (decrease in C). Although Phe was shown to be a competitive inhibitor of the major hepatic cytochrome P-450 (CYP) responsible for metabolism of [C]-BaP, CYP1A2, the high inhibition constant (K) and lack of any increase in unmetabolized [C]-BaP in plasma makes this mechanism unlikely to be responsible. Rather, co-administration of Phe reduces the absorption of [C]-BaP through a mechanism yet to be determined. This is the first study to provide evidence that, at actual environmental levels of exposure, the toxicokinetics of [C]-BaP in humans is markedly altered by the presence of a second PAH, Phe, a common component of environmental PAH mixtures.&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%">Monica L. Vermillion Maier</style></author><author><style face="normal" font="default" size="100%">Siddens, Lisbeth K</style></author><author><style face="normal" font="default" size="100%">Jamie Pennington</style></author><author><style face="normal" font="default" size="100%">Sandra Uesugi</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author><author><style face="normal" font="default" size="100%">Lane G Tidwell</style></author><author><style face="normal" font="default" size="100%">Susan C Tilton</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%">Jordan Smith</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%">Benzo[a]pyrene (BaP) metabolites predominant in human plasma following escalating oral micro-dosing with [C]-BaP.</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><dates><year><style  face="normal" font="default" size="100%">2022</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2022 Jan 15</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">159</style></volume><pages><style face="normal" font="default" size="100%">107045</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 formed by incomplete combustion of organic materials (petroleum, coal, tobacco, etc.). BaP is designated by the International Agency for Research on Cancer as a group 1 known human carcinogen; a classification supported by numerous studies in preclinical models and epidemiology studies of exposed populations. Risk assessment relies on toxicokinetic and cancer studies in rodents at doses 5-6 orders of magnitude greater than average human uptake. Using a dose-response design at environmentally relevant concentrations, this study follows uptake, metabolism, and elimination of [C]-BaP in human plasma by employing UPLC - accelerator mass spectrometry (UPLC-AMS). Volunteers were administered 25, 50, 100, and 250&amp;nbsp;ng (2.7-27 nCi) of [C]-BaP (with interceding minimum 3-week washout periods) with quantification of parent [C]-BaP and metabolites in plasma measured over 48&amp;nbsp;h. [C]-BaP median T was 30&amp;nbsp;min with C and area under the curve (AUC) approximating dose-dependency. Marked inter-individual variability in plasma pharmacokinetics following a 250&amp;nbsp;ng dose was seen with 7 volunteers as measured by the C (8.99&amp;nbsp;±&amp;nbsp;7.08&amp;nbsp;ng&amp;nbsp;×&amp;nbsp;mL) and AUC (68.6&amp;nbsp;±&amp;nbsp;64.0&amp;nbsp;fg&amp;nbsp;×&amp;nbsp;hr&amp;nbsp;×&amp;nbsp;mL). Approximately 3-6% of the [C] recovered (AUC) was parent compound, demonstrating extensive metabolism following oral dosing. Metabolite profiles showed that, even at the earliest time-point (30&amp;nbsp;min), a substantial percentage of [C] in plasma was polar BaP metabolites. The best fit modeling approach identified non-compartmental apparent volume of distribution of BaP as significantly increasing as a function of dose (p&amp;nbsp;=&amp;nbsp;0.004). Bay region tetrols and dihydrodiols predominated, suggesting not only was there extensive first pass metabolism but also potentially bioactivation. AMS enables the study of environmental carcinogens in humans with de minimus risk, allowing for important testing and validation of physiologically based pharmacokinetic models derived from animal data, risk assessment, and the interpretation of data from high-risk occupationally exposed populations.&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%">Steven G O&#039;Connell</style></author><author><style face="normal" font="default" size="100%">Nancy I Kerkvliet</style></author><author><style face="normal" font="default" size="100%">Susan Carozza</style></author><author><style face="normal" font="default" size="100%">Diana Rohlman</style></author><author><style face="normal" font="default" size="100%">Jamie Pennington</style></author><author><style face="normal" font="default" size="100%">Kim A Anderson</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">In vivo contaminant partitioning to silicone implants: Implications for use in biomonitoring and body burden.</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><dates><year><style  face="normal" font="default" size="100%">2015</style></year><pub-dates><date><style  face="normal" font="default" size="100%">9/2015</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">85</style></volume><pages><style face="normal" font="default" size="100%">182-188</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Silicone polymers are used for a wide array of applications from passive samplers in environmental studies, to implants used in human augmentation and reconstruction. If silicone sequesters toxicants throughout implantation, it may represent a history of exposure and potentially reduce the body burden of toxicants influencing the risk of adverse health outcomes such as breast cancer. Objectives of this research included identifying a wide variety of toxicants in human silicone implants, and measuring the in vivo absorption of contaminants into silicone and surrounding tissue in an animal model. In the first study, eight human breast implants were analyzed for over 1400 organic contaminants including consumer products, chemicals in commerce, and pesticides. A total of 14 compounds including pesticides such as trans-nonachlor (1.2-5.9ng/g) and p,p&#039;-DDE (1.2-34ng/g) were identified in human implants, 13 of which have not been previously reported in silicone prostheses. In the second project, female ICR mice were implanted with silicone and dosed with p,p&#039;-DDE and PCB118 by intraperitoneal injection. After nine days, silicone and adipose samples were collected, and all implants in dosed mice had p,p&#039;-DDE and PCB118 present. Distribution ratios from silicone and surrounding tissue in mice compare well with similar studies, and were used to predict adipose concentrations in human tissue. Similarities between predicted and measured chemical concentrations in mice and humans suggest that silicone may be a reliable surrogate measure of persistent toxicants. More research is needed to identify the potential of silicone implants to refine the predictive quality of chemicals found in silicone implants.&lt;/p&gt;
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