Review of the Air Quality Criteria Document for Particulate Matter

Page 7-4, Structure of the Respiratory Tract. This section would be enhanced by includingone of the well-known figures illustrating the gross structure of the respiratory tract.Page 7-9: The chapter would be enhanced by inclusion of a figure illustrating regionaldeposition in the human as a function of particle size.Page 7-24: The chapter would be enhanced by including one or more figures illustrating interspeciespatterns of total deposition and regional deposition for commonly used laboratory animalspecies and the species of interest, humans.Page 7-38: The chapter would be enhanced by including one or more figures illustrating interspeciespatterns of clearance and retained burden for commonly used laboratory animal speciesand humans.CHAPTER 8 - TOXICOLOGY – GENERAL COMMENTSThe introduction of the chapter could be strengthened with a better linkage to the epidemiologychapter. The epidemiology chapter relates findings from multiple studies showing an increase inhealth effects, primarily cardio-respiratory effects especially in susceptible populationsassociated with various PM indicators when assessed in larger populations (usually a study sizeof over 10,000 mortality or morbidity events times study days) with a relatively low prevalencerate for the adverse events of concern. Restating this at the beginning of the Toxicology chapterwill help provide a setting for consideration of the toxicological findings on PM in humans andlaboratory animals under controlled exposure conditions. In my opinion, the toxicologicalfindings have generally not been very informative, as to how PM may be pathogenic in humansor in identifying specific putative causative agents with PM. I suggest that the lack of progressrelates to the blunt “statistical” nature of current toxicological methods for tackling lowprobability of added effects when the diseases of concern have low prevalence rate outcomeseven in susceptible populations.It would also be useful if the introduction of the chapter could identify the challenge of movingbeyond characterizing whether a specific material is hazardous; i.e., capable of causing adverseeffects at any level of exposure, to the critical issue of the relevance of the findings at typicalambient concentrations of PM.The section of the chapter addressing susceptible populations should briefly consider the issue ofcigarette smoking as a risk factor. I submit that the vast majority of increased health effectsassociated with PM in adult populations are observed in smokers or former smokers. Thesepopulations contribute a disproportionate number of individuals with cardio-respiratory diseaseand, thus, are the major susceptible population at risk from PM-related disease. It is noteworthythat to date a well-defined animal model has not been found for cigarette smoking inducedcardio-respiratory disease. Smoking-related diseases develop slowly and are usually manifestedlate in life. The absence of such models is also reflected in the lack of well-developed andvalidated models of the common PM-related cardio-respiratory diseases. The minimal nature ofrespiratory disease in young rats exposed for months to heavy doses of cigarette smoke may alsohelp rationalize the relatively refractory nature of rats exposed for modest lengths of time to PMand constituents.The section of Chapter 8 on in vitro exposures lacks information that would help place the invitro studies in perspective relative to in vivo exposures of humans to ambient PM. In commentson Chapter 7, I noted the need for calculations of deposition rates and steady state burdens ofPM in humans exposed to various levels of ambient PM. Such information presented in detail inChapter 7 could be summarized in Chapter 8 and provide a metric for comparison to the levelsused in in vitro studies. A review of these in vitro studies suggests that the concentrations of PMand constituents studied are orders of magnitude in excess of any concentrations likely to beA - 62