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.

BackgroundHormesis is a specific type of nonmonotonic dose response whose occurrence has been documented across a broad range of biological models, diverse types of exposure, and a variety of outcomes. The effects that occur at various points along this curve can be interpreted as beneficial or detrimental, depending on the biological or ecologic context in which they occur.ObjectiveBecause hormesis appears to be a relatively common phenomenon that has not yet been incorporated into regulatory practice, the objective of this commentary is to explore some of its more obvious public health and risk assessment implications, with particular reference to issues raised recently within this journal by other authors.DiscussionHormesis appears to be more common than dose–response curves that are currently used in the risk assessment process [e.g., linear no-threshold (LNT)]. Although a number of mechanisms have been identified that explain many hormetic dose–response relationships, better understanding of this phenomenon will likely lead to different strategies not only for the prevention and treatment of disease but also for the promotion of improved public health as it relates to both specific and more holistic health outcomes.ConclusionsWe believe that ignoring hormesis is poor policy because it ignores knowledge that could be used to improve public health.

Mortality was updated to the end of 1982 for 594 employees exposed to benzene who had been studied previously and for an additional 362 exposed workers not studied previously. Cause specific mortality comparisons were made using United States white male, age, and calendar year adjusted rates. Total mortality was observed to have been significantly below expectation, and this was particularly evident for deaths from accidental causes. Mortality from skin cancer was significantly raised, although there were no unusual or common characteristics among the affected individuals which would suggest a link with exposure to benzene. A non-significant excess of total deaths from leukaemia was noted based on four observed cases; however, all four were myelogenous leukaemias and this represented a significant excess in that subcategory. These and other deaths of possible interest are reviewed in detail. Analyses by work area, duration of exposure, and cumulative dose index did not show patterns suggestive of a causal association between exposure to benzene and any particular cause of death.

BOND GG, BODNER KM, OLSEN GW, COOK RR. Mortalit y among wor kers engaged in the development or manufactu re of styrene-based produ cts -an update . Scand J Work Environ Health 1992; 18:145-54. Mortality was updated another 11 years through 1986 for a pr eviously studied cohort of 2904 male chemical workers who were potent ially exposed to styrene and related materials for a year or more between 1937 and 1971. Substantial deficits in mortality from all causes and total cancer were observed in the cohort when it was compared with white males in the United States, and also other chemical worker s who were unexposed to styrene-based products. Mortality from leukemia was slightly less than expected during the updated period , in contrast to an excess of lymphatic leukemia observed in the original period. Yet small elevations in risk of other types of lymphatic cancer, particularly multiple myeloma, persisted. The risk of these cancers did not increase with estimated inten sity or duration of styrene exposure. The findings are discussed in context with those of studies of similarly exposed workers in related industries.

Concern for many women with breast implants has been focused on three topics: cancer (both breast and other cancers), delayed detection of breast cancer, and increased breast cancer recurrence or decreased length of survival. In this study, a qualitative review of the literature on these subjects was conducted, coupled with a meta-analysis of the risk for breast cancer or other cancers (excluding that of the breast). Researchers have consistently found no persuasive evidence of a causal association between breast implants and any type of cancer. The meta-analysis results obtained by combining the epidemiology studies support the overall conclusion that breast implants do not pose any additional risk for breast cancer (relative risk, 0.72; 95% confidence interval, 0.61 to 0.85) or for other cancers (relative risk, 1.03; 95% confidence interval, 0.87 to 1.24). This analysis suggests that breast implants may confer a protective effect against breast cancer. Women with implants should be reassured by the consistency of scientific studies which have uniformly determined that, compared with women without implants, they are not at increased risk for cancer, are not diagnosed with later-stage breast malignancies, are not at increased risk for breast cancer recurrence, and do not have a decreased length of survival.

If the hormetic dose-response were accepted as the default dose-response model for risk assessment it could have important implications for environmental exposure standards for noncarcinogens and especially for carcinogens. Most notably it would lead to the recognition that carcinogens act via a threshold process rejecting the concept of linearity at low doses. The hormetic concept also provides agencies with a broader range of toxicologically-based exposure options, which permit a consideration for avoiding harm, as well as possibly enhancing benefits for both normal and high risk segments of the population. By dismissing hormesis, regulatory agencies such as EPA deny the public the opportunity for optimal health and avoidance of disease.

A recent cohort mortality study of male, hourly wage employees of a large Michigan chemical production and research facility had found a greater than expected number of deaths coded to liver and biliary tract cancer. In response, an additional investigation was then undertaken of the 44 liver and biliary tract cancer deaths observed between 1940 and 1982. A random sample (N = 1,888) of subjects was selected from the total cohort (N = 21,437) to serve as referents. Company work history records were used to classify cases and referents by work area assignment and potential for exposure to 11 selected chemical agents which have been shown to produce cancer of the liver or biliary passages in experimental animals. Statistically significant associations in both positive and negative directions were found for several work areas within the facility. A suggestive association was found for vinyl chloride monomer, based on five cases with presumed exposure.

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