Due to their exceptionally low water solubilities, polychlorinated dibenzo-p-dioxins and -furans (PCDD/Fs) are strongly and extensively bound to the solid particles of sediments and soils, especially charcoal-like pyrogenic carbonaceous matter (PCM, [1]), amorphous organic matter (AOM), and clay minerals. The United States Environmental Protection Agency (USEPA) conservatively assumes that 100% of soil-bound PCDD/Fs are bioavailable to mammals, including humans [2], while measured bioavailabilities of PCDD/Fs in real soils are far lower [3-13]. Real mammalian bioavailabilities are poorly understood, but we have recently advanced the science of PCDD/F bioavailability from soils by relating it to the properties of individual particle types: We have shown that PCDDs that are bound to AOM, clay minerals, or porous-silica particles are indeed 100% bioavailable (relative to those in corn oil) [14-18]. In contrast, we showed that PCDDs bound to a special kind of PCM called activated carbon (AC) had bioavailabilities of zero to mice [19, 20] and protected mammalian health. Our recent work provides two hypotheses to inform risk assessment and remediation strategies for PCDD/F-contaminated sites: 1) Low levels of PCM are ubiquitous in soils and sediments, so AC-like domains in PCM may be responsible for lowering the mammalian bioavailabilities of PCDD/Fs in real soils, and 2) Our understanding of soil particle types simplifies the complexity of soils enough that we can directly and mechanistically test whether AC amendment of PCDD/F-contaminated soils has potential to be protective of human and ecosystem health by minimizing mammalian bioavailability. Remediation using AC amendment was proposed long ago, because it is far cheaper and less environmentally disruptive than removing contaminated soils to hazardous-waste landfills, but regulators cannot adopt AC as a remedy because no one has shown that AC amendments are truly protective of mammalian and human health. We propose a set of experiments designed to rigorously test the hypothesis that PCDDs bound to AC amendments are no longer bioavailable to mammals, and thereby help USEPA and state regulators critically assess this promising treatment for remediation of PCDD/F-contaminated Superfund sites: We will track the full mass balance of PCDDs in soils after AC has been added, and then administer these soils orally to mice and measure PCDD bioavailability and mass balance in the mice. For the first time, we will directly measure the kinetics of PCDD accumulation in AC amendments and compare these with measured kinetics of soil-PCDD mammalian bioavailability. This work will inform risk assessment by supplying data for six practical criteria that EPA uses [21] to select Superfund remedies, including whether AC amendments are likely to protect human and ecosystem health, the kinetics of their short-term bioavailability reduction, and the longer- term stabilities of PCDD-AC complexes once they form. In sum, Pro...