Hierarchical mean and covariance structure models

Purpose of this paper is the formulation of a generalized latent variable model. A variety of mixed measurement and structural relationship models for metric, classified metric, ordered categorical, dichotomous and one- and double-sided censored indicators is linked to metric latent variables by three construction principles. These involve the combination of threshold concepts, simultaneous equation systems and hierarchical factor analytical models. The LISREL model is shown to be a special case. While focusing on construction principles and important special cases of the general model, some references to estimation strategies are given. This research was partially supported by a dissertation grant of theStudienstiftung des Deutschen Volkes. Comments and suggestions on earlier drafts by Gerhard Arminger, Günter Bamberg, Bernd Korzen and Andreas Schepers are gratefully acknowleged.     

Cardiac Sensitization Thresholds of Halon Replacement Chemicals Predicted in Humans by Physiologically-Based Pharmacokinetic Modeling

Human exposure to halons and halon replacement chemicals is often regulated on the basis of cardiac sensitization potential. The dose-response data obtained from animal testing are used to determine the no observable adverse effect level (NOAEL) and lowest observable adverse effect level (LOAEL) values. This approach alone does not provide the information necessary to evaluate the cardiac sensitization potential for the chemical of interest under a variety of exposure concentrations and durations. In order to provide a tool for decision-makers and regulators tasked with setting exposure guidelines for halon replacement chemicals, a quantitative approach was established which allowed exposures to be assessed in terms of the chemical concentrations in blood during the exposure. A physiologically-based pharmacokinetic (PBPK) model was used to simulate blood concentrations of Halon 1301 (bromotrifluoromethane, CF₃Br), HFC-125 (pentafluoroethane, CHF₂CF₃), HFC-227ea (heptafluoropropane, CF₃CHFCF₃), HCFC-123 (dichlorotrifluoroethane, CHCl₂CF₃), and CF₃I (trifluoroiodomethane) during inhalation exposures. This work demonstrates a quantitative approach for use in linking chemical inhalation exposures to the levels of chemical in blood achieved during the exposure.