Modeling Receptor-Mediated Processes with Dioxin: Implications for Pharmacokinetics and Risk Assessment

Dioxin (2,3,7,8-tetrachlorodibenzo- p -dioxin; TCDD), a widespread polychlorinated aromatic hydrocarbon, caused tumors in the liver and other sites when administered chronically to rats at doses as low as 0.01 μg/kg/day. It functions in combination with a cellular protein, the Ah receptor, to alter gene regulation, and this resulting modulation of gene expression is believed to be obligatory for both dioxin toxicity and carcinogenicity. The U.S. EPA is reevaluating its dioxin risk assessment and, as part of this process, will be developing risk assessment approaches for chemicals, such as dioxin, whose toxicity is receptor-mediated. This paper describes a receptor-mediated physiologically based pharmacokinetic (PB-PK) model for the tissue distribution and enzyme-inducing properties of dioxin and discusses the potential role of these models in a biologically motivated risk assessment. In this model, ternary interactions among the Ah receptor, dioxin, and DNA binding sites lead to enhanced production of specific hepatic proteins. The model was used to examine the tissue disposition of dioxin and the induction of both a dioxin-binding protein (presumably, cytochrome P4501A2), and cytochrome P4501A1. Tumor promotion correlated more closely with predicted induction of P4501A1 than with induction of hepatic binding proteins. Although increased induction of these proteins is not expected to be causally related to tumor formation, these physiological dosimetry and gene-induction response models will be important for biologically motivated dioxin risk assessments in determining both target tissue dose of dioxin and gene products and in examining the relationship between these gene products and the cellular events more directly involved in tumor promotion.     

How Danish companies plan

A study of 12 Danish firms shows that many are trying to make the transition from a budgeting to a planning orientation. Quantitative techniques are de-emphasized; niche strategies are prevalent. Some firms are using rather unusual approaches which are worth monitoring.     

The Status of Sociology within the Academy: Where We Are, Why We’re There, and How to Change It

We present data from a survey of deans at colleges and universities throughout the USA on the relative status of disciplines. Findings indicate that the relative status of Sociology within the academy is low, although there are several specific areas of high status—namely, concerning community involvement and engagement. Our analyses also investigate which areas of activity are most closely associated with the overall prestige of disciplines. Findings indicate that research-oriented activities are the most influential, while student-oriented activities have a more ambivalent association with status. Based on those findings, we offer suggestions for raising the status of the discipline, based on the cultivation of natural synergies linking research, community engagement, student training, and focusing on the benefits of establishing social science research centers associated with Sociology departments.     

AMISH ABUNDANCE: HOW THE PLAIN PEOPLE PROSPER

Abundance is defined as having enough of whatever one craves and/or needs in life. Thus, one can speak of physical abundance as being distinct from spiritual or social abundance. Abundance is an inherently personal, experiential concept, not amenable to objective, economic measurement such as income. The Amish people of Canada and USA provide an excellent case study in avoiding poverty traps and achieving a sustainable, abundant and healthy life, on very low incomes. This study of Amish culture has important social lessons and policy implications, both on the micro and the macro level. The study also reveals how the social and material security which the Amish enjoy, is however, achieved at the cost of severely circumscribed personal freedoms of thought and action.