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Asphaltene properties vary with separation method and sometimes with individual technique. Factors such as contact time, solvent-to-crude oil ratio, and temperature influence asphaltene precipitation and are somewhat standardized. However, the final step in most separations, washing the asphaltene filter cake with solvent, is not standardized. Asphaltene properties can be very sensitive to small amounts of resins and therefore may be sensitive to the amount of washing. Asphaltenes were extracted with three different levels of washing from four source oils (Athabasca, Cold Lake, Lloydminster, and Peace River). In all cases, increased washing decreased asphaltene yield and slightly increased asphaltene density. Increased washing significantly increased molar mass and decreased the solubility of the extracted asphaltenes. A new washing method using a Soxhlet apparatus removed the largest amount of resinous material and yielded asphaltenes with significantly different properties from conventionally washed asphaltenes. Since more resinous material was removed, the Soxhlet method allows a more direct comparison between asphaltenes from different sources. Asphaltenes were also extracted using three standard separation methods, IP 143, ASTM D4124, and a method proposed by Speight. Some property variations between the methods were observed and a set of criteria to obtain consistent samples is proposed.

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The precipitation and redissolution of asphaltenes from mixtures of Athabasca bitumen and n-heptane was measured over time in both air and nitrogen atmospheres at 23 °C. In air, it appears that oxidation of the bitumen increased the asphaltene yield for as long as the experiments were conducted; that is, for several months. When oxidation effects are excluded, asphaltene precipitation and redissolution both appear to reach steady state within 24 h. A hysteresis between asphaltene precipitation and redissolution was also observed in both atmospheres. The hysteresis was exaggerated in the air atmosphere due to oxidation effects. In both air and nitrogen atmospheres, complete reversibility was attained when the heptane-to-bitumen ratio was reduced to 1.5 cm3/g. The hysteresis is attributed to an energy barrier to asphaltene dissociation. As more heptane is added, the asphaltenes likely self-associate to higher apparent molar masses. When the heptane is removed, the asphaltenes may remain in the higher association state and hence precipitate to a greater extent than before at a given heptane-to-bitumen ratio. If the system is heated, the asphaltene yields return to their original values, indicating that the original association state can be restored.

The carcinogenic potential of roxadustat (FG-4592), a novel orally active, heterocyclic small molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) enzymes in clinical development for treatment of anemia, was evaluated in CD-1 mice and Sprague Dawley rats. Inhibition of HIF-PH by roxadustat leads to a rapid increase in cytoplasmic HIF-α concentrations, followed by translocation of HIF-α to the nucleus and upregulation of HIF-responsive genes, including erythropoietin. Roxadustat was dosed by oral gavage 3 times weekly (TIW) for up to 104 weeks in mice at 0, 15, 30, and 60 mg/kg and in rats at 0, 2.5, 5, and 10 mg/kg. Treatment-associated changes in hematology parameters were consistent with the pharmacologic activity of roxadustat and included elevations in hematocrit in mice at 30 and 60 mg/kg TIW and elevations in erythrocyte count, hemoglobin, hematocrit, and red cell distribution width in rats at 10 mg/kg TIW. No increase in mortality or neoplastic effects compared with vehicle controls was observed after roxadustat treatment in either species. No treatment-related nonneoplastic findings were observed in mice, whereas nonneoplastic microscopic findings in rats were limited to atrial/aortic thromboses at 10 mg/kg TIW males and bone marrow hypercellularity in all treated male and female groups, consistent with the pharmacology of roxadustat. In conclusion, roxadustat administered by oral gavage to mice and rats TIW for up to 104 weeks resulted in dose-dependent exposure and hematologic effects with no effect on survival or development of neoplastic lesions at up to 60 mg/kg in mice and up to 10 mg/kg in rats.