Melvin E. Andersen

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One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation of H2O2. In(More)
Methylene chloride (dichloromethane, DCM) is metabolized by two pathways: one dependent on oxidation by mixed function oxidases (MFO) and the other dependent on glutathione S-transferases (GST). A physiologically based pharmacokinetic (PB-PK) model based on knowledge of these pathways was used to describe the metabolism of DCM in four mammalian species(More)
This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically(More)
A physiologically based pharmacokinetic model describing the disposition of chloroform in mice, rats, and humans was developed. This model was designed to facilitate extrapolations from high doses, such as those used in chronic rodent studies, to low doses that humans may be exposed to in the workplace or the environment. Kinetic constants for mice and rats(More)
Manganese (Mn)-deficiency or Mn-excess can lead to adverse biological consequences. Central nervous system tissues, rich in dopaminergic neurons, are the targets whether the Mn gains entrance by inhalation, oral ingestion, or intravenous administration. Risk assessments with Mn need to ensure that brain concentrations in the globus pallidus and striatum(More)
A physiologically based pharmacokinetic model which describes the behavior of inhaled styrene in rats accurately predicts the behavior of inhaled styrene in humans. The model consists of a series of mass-balance differential equations which quantify the time course of styrene concentration within four tissue groups representing (1) highly perfused organs,(More)
Dichloromethane (methylene chloride, DCM) and other dihalomethanes are metabolized to carbon monoxide (CO) which reversibly binds hemoglobin and is eliminated by exhalation. We have developed a physiologically based pharmacokinetic (PB-PK) model which describes the kinetics of CO, carboxyhemoglobin (HbCO), and parent dihalomethane, and have applied this(More)
Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) compounds associated with surface protection product manufactures are distributed globally. The 3-5-year half-lives, reproductive and liver toxicity in animals, and lack of understanding of the factors regulating retention in the body have led to a world-wide public concern for use of these(More)
In 2007, the U.S. National Academy of Sciences released a report, Toxicity Testing in the 21st Century: A Vision and a Strategy, that envisions a not-so-distant future in which virtually all routine toxicity testing would be conducted in human cells or cell lines in vitro by evaluating cellular responses in a suite of toxicity pathway assays using(More)