Although the epidemiologic associations between urban particulate air pollution and human mortality and morbidity have been accumulating for several years, the causal agents (a specific chemical component, a specific particle size range, one or more pollutant combinations, etc.), and the physiological mechanisms behind the associations have yet to be identified. Significant questions regarding confounding effects due to weather, indoor air pollutant exposures and co-pollutants (that accompany particulate matter) stubbornly remain. The events in the United States began with recent epidemiological associations, followed by a lawsuit forcing the US EPA to accelerate the standard-setting process, and finally controversy over the scientific basis of the new standard. In contrast to the potential risks posed by particulate air pollution, many of the sources of such particles are positive contributors to human health; control measures to meet the proposed standard may therefore produce offsetting enhanced mortality and morbidity. In order to establish the information required for well-informed public health policies, a substantial research program is needed because of uncertainties relating to, the affected individuals, the potential causal agents, and the consequences of particle-control activities. Not only are the remaining scientific questions significant, but the particle exposure/health effects associations also call into question some of the current scientific assumptions relating to the nature of effects of population exposures to low concentrations of pollutants.

Scientists, regulators, legislators, and segments of industry and the lay public are attempting to understand and respond to epidemiology findings of associations between measures of modern particulate air pollutants (PM) and adverse health outcomes in urban dwellers. The associations have been interpreted to imply that tens of thousands of Americans are killed annually by small daily increments in PM. These epidemiology studies and their interpretations have been challenged, although it is accepted that high concentrations of air pollutants have claimed many lives in the past. Although reproducible and statistically significant, the relative risks associated with modern PM are very small and confounded by many factors. Neither toxicology studies nor human clinical investigations have identified the components and/or characteristics of PM that might be causing the health-effect associations. Currently, a massive worldwide research effort is under way in an attempt to identify whom might be harmed and by what substances and mechanisms. Finding the answers is important, because control measures have the potential not only to be costly but also to limit the availability of goods and services that are important to public health.

Pulmonary dosimetry models provide quantitative information on the locations and amounts of deposition of inhaled toxins, both gaseous and particulate. The specification of location may be quite broad, as in an entire region (head, tracheobronchial airways, or parenchyma), or very specific, for example within each of the many generations of the tracheobronchial tree. The uses for such information include proper selection of laboratory animalspecies in toxicologic studies, refined interpretation of laboratory animal toxicologic data, and prediction of potential sites of high local-injury from inhaled materials. Further, dosimetry models tend to identify the roles of relevant factors in potential lung injury. Such relevant factors may be physical-chemical (particle size, gas water solubility, etc.), physiologic (air flow patterns, mucus characteristics, etc.), or anatomical (airway dimensions, branch angles, etc.).Predictive dosimetry models are of two major types, theoretical and empirical. In both types, the ultimate requirements for acceptability are the same; they must be realistic, must be validated, and must be of use in predicting whatwould occur in unexamined circumstances. Theoretical dosimetry models are constructs which usually begin with simplifications of the real world. Such simplifications occur in theselection of equations describing movement of gases and particles toward airway walls, use of manageable airflow descriptions, and incorporation of anatomical geometries that represent averages of actual lung morphology. Such models are later made more sophisticated by the incorporation of additional complexities.Empirical modeling usually involves analysis of dosimetric data obtained in constructed hollow models, or less often in actual lungs, which have been exposed to airborne materialunder conditions simulating breathing. The analysis of such data permits development of mathematical relationships that describe the distribution of material deposited. Such relationships are then used to predict deposition patterns in unstudied circumstances. In addition to their value for predicting dose patterns, the equations that result from theoretical and empirical models can shed light on the mechanisms which control such dose patterns. Knowledge regarding mechanism is a fuel which fires scientific inquiry, stimulating the design of future studies. © 1984 by Hemisphere Publishing Corporation.

Toxicity Testing in the 21st Century: A Vision and a Strategy (NRC, 2007) presents a bold plan for chemical toxicity testing that replaces whole-animal tests with cell-culture, genetic, other in-vitro techniques, computational methods, and human monitoring. Although the proposed vision is eloquently described, and recent advances in in-vitro and in-silico methods are impressive, it is difficult believe that replacing in-vitro testing is either practical or wise. It is not clear that the toxicity-related events that occur in whole animals can be adequately replicated using the proposed methods. Protecting public health is a serious endeavor that should not be limited by denying animal testing. Toxicologists and regulators are encouraged to read the report, carefully consider its implications, and share their thoughts. The vision is for too important to ignore.

An exploded wire aerosol generator was evaluated using test aerosols derived from silver wires and results were compared with existing published information on exploded wire particles. Aerosol properties relevant to inhalation studies were emphasized. Primary particles were spherical, metallic, and distributed nearly lognormally by volume (geometric standard deviation about 1·5) with count median diameters between 0-05 and 0-008 μm. The primary particle size decreased as the explosion energy per unit mass of wire was increased. Primary particles rapidly formed agglomerates of up to hundreds of spherical units but an air blast aimed at and synchronized with the wire explosion was successful in reducing agglomeration. Agglomerate aerosols with submicron aerodynamic diameters were produced by rapidly diluting the explosion zone after the air blast. Agglomerates of 0-026 μm count median diameter primary particles had measured specific surfaces of 16-4 m3/g and solubility rate constants of 10 μg/cm2 per day in a lung fluid simulant containing protein. The relevance of exploded wire agglomerates to inhalation studies is briefly discussed. © 1972.

The Third Colloquium on Particulate Matter and Human Health addressed the roles that inhaled particle dosimetry plays in understanding the potential health risks of human populations exposed to particulate air pollution. Nineteen papers, including posters, were presented that addressed particle deposition and clearance in both humans and laboratory animals. The effects of age, gender, and illness were addressed, as well as ultrafine particles and correlations between particle deposits and tissue pathology. The papers and related discussions also illuminated some important gaps in knowledge, such as the accuracy of dosimetry predictions for individuals; the underrepresentation of susceptible populations; the movement of deposited particles to nonlung tissues and organs; and the accuracy of extrapolations across species. Although current dosimetric information is useful for understanding the effects of particulate air pollution, several unsolved problems remain.