3,3',4,4',5'-Pentachlorobiphenyl (PCB126) is a carcinogenic environmental pollutant and its toxicity is mediated through binding with aryl hydrocarbon receptor (AhR). Earlier, we found that PCB126 treated F344 rats had 110-400 times higher PCB126 concentration in the liver than in the fat. Protein binding was suspected to be a major factor for the high liver concentration of PCB126 despite its high lipophilicity. In this research, we conducted a combined pharmacokinetic/pharmacodynamic study in male F344 rats. In addition to blood and tissue pharmacokinetics, we use the development of hepatic preneoplastic foci (glutathione-S-transferase placental form [GSTP]) as a pharmacodynamic endpoint. Experimental data were utilized for building a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model. PBPK/PD modeling was consistent with the experimental PK and PD data. Salient features of this model include: (1) bindings between PCB126 and hepatic proteins, particularly the multidrug resistance-associated protein (Mrp2), a protein transporter; (2) Mrp2-mediated excretion; and (3) a relationship between area under the curve of PCB126 in the livers and % volume of GSTP foci. Mrp2 involvement in PCB126 pharmacokinetics is supported by computational chemistry calculation using a three-dimensional quantitative structure-activity relationship model of Mrp2 developed by S. Hirono et al. (2005, Pharm. Res. 22, 260-269). This work, for the first time, provided a plausible role of a versatile hepatic transporter for drugs, Mrp2, in the disposition of an important environmental pollutant, PCB126.
Raymond S. H. Yang, Quantitative and Computational Toxicology Group, Department of Environmental and Radiological Health Sciences, Colorado State University, 137A Physiology Building, Fort Collins, CO 80523-1680
Links with this icon indicate that you are leaving the CDC website.
The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
You will be subject to the destination website's privacy policy when you follow the link.
CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website.
For more information on CDC's web notification policies, see Website Disclaimers.
CDC.gov Privacy Settings
We take your privacy seriously. You can review and change the way we collect information below.
These cookies allow us to count visits and traffic sources so we can measure and improve the performance of our site. They help us to know which pages are the most and least popular and see how visitors move around the site. All information these cookies collect is aggregated and therefore anonymous. If you do not allow these cookies we will not know when you have visited our site, and will not be able to monitor its performance.
Cookies used to make website functionality more relevant to you. These cookies perform functions like remembering presentation options or choices and, in some cases, delivery of web content that based on self-identified area of interests.
Cookies used to track the effectiveness of CDC public health campaigns through clickthrough data.
Cookies used to enable you to share pages and content that you find interesting on CDC.gov through third party social networking and other websites. These cookies may also be used for advertising purposes by these third parties.
Thank you for taking the time to confirm your preferences. If you need to go back and make any changes, you can always do so by going to our Privacy Policy page.