%0 Journal Article %J Chem Biol Interact %D 2023 %T Impact of phenanthrene co-administration on the toxicokinetics of benzo[a]pyrene in humans. UPLC-accelerator mass spectrometry following oral microdosing. %A Monica L. Vermillion Maier %A Siddens, Lisbeth K %A Jamie Pennington %A Sandra Uesugi %A Labut, Edwin M %A Vertel, Emily A %A Kim A Anderson %A Lane G Tidwell %A Susan C Tilton %A Ted J Ognibene %A Kenneth Turteltaub %A Jordan Smith %A Williams, David E %X

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 h following a dose of [C]-BaP (50 ng, 5.4 nCi) or the same dose of [C]-BaP plus Phe (1250 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.

%B Chem Biol Interact %V 382 %P 110608 %8 2023 Jun 25 %G eng %R 10.1016/j.cbi.2023.110608 %0 Journal Article %J Environ Int %D 2015 %T In vivo contaminant partitioning to silicone implants: Implications for use in biomonitoring and body burden. %A Steven G O'Connell %A Nancy I Kerkvliet %A Susan Carozza %A Diana Rohlman %A Jamie Pennington %A Kim A Anderson %X

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'-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'-DDE and PCB118 by intraperitoneal injection. After nine days, silicone and adipose samples were collected, and all implants in dosed mice had p,p'-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.

%B Environ Int %V 85 %P 182-188 %8 9/2015 %G eng %R 10.1016/j.envint.2015.09.016