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The ability of either beta-adrenergic blockade or bilateral renal denervation to alter erythropoietin (ESF) production in rabbits exposed to hypobaric hypoxia was studied. ESF elaboration during 5 h of exposure to hypoxia was not affected by beta-blockade, but was markedly reduced by prior surgical denervation of both kidneys. After 18 h of hypoxia plasma ESF levels in renal denervated rabbits did not differ significantly from those of sham-operated controls. Previous studies have shown that ESF production during this more prolonged exposure to hypoxia was significantly inhibited by some beta-adrenergic blocking agents. Combined renal denervation and beta-blockade were more effective than renal denervation alone in attenuating ESF production during 5 h of exposure to hypoxia. However, ESF elaboration during 18 h of hypoxia was significantly greater in animals with combined denervation and beta-blockade than in control rabbits. These results suggest the existence of two distinct mechanisms for ESF production in rabbits exposed to hypobaric hypoxia.

Trichloroethylene (TCE), an environmental contaminant of National concern, is the focus of a new health risk assessment process incorporating the Proposed Cancer Risk Assessment Guidelines. This paper describes not only how TCE became an environmental problem for the Air Force, but also details the new Risk Assessment process envisioned by the Environmental Protection Agency's (EPA) National Center for Environmental Assessment (NCEA). Insights on epidemiological evaluations, both past and future, and their impact on the cancer classification of TCE are discussed. Examples of how physiologically based pharmacokinetics and dose-response characterization described in the new Cancer Guidelines are applied to TCE are provided. In addition, a variety of modeling techniques are discussed for the development of reference doses (oral exposure) and reference concentrations (inhalation exposures) for TCE. Finally, the role of risk communication is included. This new process provides an example of how interagency (EPA, Department of Defense. Department of Energy) and extramural (industry, academia) partnerships can provide greater gains to the nation, as a whole, than any of the parts on their own.

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