a b s t r a c tInhaled aerosol dose models play critical roles in medicine, the regulation of air pollutants and basic research. The models fall into several categories: traditional, computational fluid dynamical (CFD), physiologically based pharmacokinetic (PBPK), empirical, semi-empirical, and "reference". Each type of model has its strengths and weaknesses, so multiple models are commonly used for practical applications. Aerosol dose models combine information on aerosol behavior and the anatomy and physiology of exposed human and laboratory animal subjects. Similar models are used for in-vitro studies. Several notable advances have been made in aerosol dose modeling in the past 80 years. The pioneers include Walter Findeisen, who in 1935 published the first traditional model and established the structure of modern models. His model combined aerosol behavior with simplified respiratory tract structures. Ewald Weibel established morphometric techniques for the lung in 1963 that are still used to develop data for modeling today. Advances in scanning techniques have similarly contributed to the knowledge of respiratory tract structure and its use in aerosol dose modeling. Several scientists and research groups have developed and advanced traditional, CFD, and PBPK models. Current issues under study include understanding individual and species differences; examining localized particle deposition; modeling non-ideal aerosols and nanoparticle behavior; linking the regions of the respiratory tract airways from nasal-oral to alveolar; and developing sophisticated supporting software. Although a complete history of inhaled aerosol dose modeling is far too extensive to cover here, selected highlights are described in this paper.

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The toxicity and carcinogenicity of nickel compounds are considered in three broad categories: (1) systemic toxicology, (2) molecular toxicology, and (3) carcinogenicity. The systemic toxicity of nickel compounds is examined based upon human and animal studies. The major organs affected are discussed in three categories: (1) kidney, (2) immune system, and (3) other organs. The second area of concentration is molecular toxicology, which will include a discussion of the chemistry of nickel, its binding to small and large molecular weight ligands, and, finally, its cellular effects. The third major area involves a discussion of the carcinogenicity and genotoxicity of nickel compounds. This section focuses on mechanisms, using studies conducted in vivo and in vitro. It also includes a discussion of the assessment of the carcinogenicity of nickel compounds.