Learn More
This study presents a nonlinear system of delay differential equations to model the concentrations of five hormones important for regulation and maintenance of the menstrual cycle. Linear model components for the ovaries and pituitary were previously analyzed and reported separately. Results for the integrated model are now presented here. This model(More)
The concept that the product of the concentration (C) of a substance and the length of time (t) it is administered produces a fixed level of effect for a given endpoint has been ascribed to Fritz Haber, who was a German scientist in the early 1900s. He contended that the acute lethality of war gases could be assessed by the amount of the gas in a cubic(More)
In this study, a mathematical model is developed for the production of the ovarian hormones (estradiol, progesterone, and inhibin) with input functions which represent blood levels of the gonadotropin hormones (luteinizing hormone and follicle stimulating hormone). A 9-dimensional system of linear, nonautonomous, ordinary differential equations tracks the(More)
A panel of experts in physiologically based pharmacokinetic (PBPK) modeling and relevant quantitative methods was convened to describe and discuss model evaluation criteria, issues, and choices that arise in model application and computational tools for improving model quality for use in human health risk assessments (HHRAs). Although publication of a PBPK(More)
Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia, pancytopenia, and acute myelogenous leukemia. However, the risks of leukemia at low exposure concentrations have not been established. A combination of metabolites(More)
Benzene (C(6)H(6)) is a highly flammable, colorless liquid. Ubiquitous exposures result from its presence in gasoline vapors, cigarette smoke, and industrial processes. Benzene increases the incidence of leukemia in humans when they are exposed to high doses for extended periods; however, leukemia risks in humans subjected to low exposures are uncertain.(More)
Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene are well documented and include aplastic anemia and pancytopenia. Some individuals exposed repeatedly to cytotoxic concentrations of benzene develop acute myeloblastic anemia. It has been hypothesized that metabolism of(More)
The application of metabolic control theory (MCT), or other methods of determining metabolic sensitivity to the rates of specific cellular processes, such as enzymatic reactions, requires knowledge of the elasticity coefficients (system partial derivatives) for the processes under study. Although rate equations are available in the literature for some(More)
BACKGROUND The U.S. EPA's Integrated Risk Information System (IRIS) completed an updated toxicological review of dichloromethane in November 2011. OBJECTIVES In this commentary we summarize key results and issues of this review, including exposure sources, identification of potential health effects, and updated physiologically based pharmacokinetic (PBPK)(More)
In this commentary, we summarize exposure sources and the major findings, advancements , critical issues, and future research needs identified in the IRIS assessment, particularly with respect to the physiologically based pharmacokinetic (PBPK) model structure , approaches used to incorporate sensitivity based on genotype, and other sources of variability(More)