Review of the Air Quality Criteria Document for Particulate Matter

Line 19: Was the change in heart rate variability an increase rather than adecrease? I think what should be stated here is that the ratio of low and high frequency band ofHRV decreased.Page 8-32, lines 10-19: Here the two different dog studies by Godleski and Muggenbergare compared, however, the studies are significantly different from each other in that Godleskiused CAPS and Muggenberg used ROFA, the particle size might also have been very different.Thus, it is difficult to compare the different findings between the two studies given also thatstorage of ROFA could have played an important role in altering its toxicity. It should also beconsidered that the dogs in the study by Godleski were exposed via a tracheostomy tube.Page 8-34, line 4: I suggest to change “high concentrations” to “only highconcentrations.”Page 8-37, lines 28-29: The exposure concentration of ROFA was 15 mg/m 3 ?Page 8-38, line 17: Change “Teflon particles” to “ultrafine PTFE fumes”.Page 8-39, line 9: In this section of age-related differences in PM effects, the studies byElder et al. should be included, they describe effects of inhaled carbonaceous model particles inLPS-sensitized rats of old and young age (Elder, A.C.P., Gelein, Finkelstein, J.N., Cox, C. and Oberdörster,G. Pulmonary inflammatory response to inhaled ultrafine particles is modified by age, ozone exposure, and bacterialtoxin. Inhalation Toxicology 12 (Suppl. 4): 227-246, 2000; Elder, A.C.P., Gelein, R., Finkelstein, J.N., Cox, C. andOberdörster, G. Endotoxin priming affects the lung response to ultrafine particles and ozone in young and old rats.Inhalation Toxicology 12 (Suppl.): 85-98, 2000).Page 8-40, line 2: Is a fibrotic response an important endpoint for ambient PM?Page 8-39 thru 8-45: In this section on genetic susceptibility to inhaled particles, adiscussion on the dose levels used in the different types of studies would be useful to put them inperspective to ambient levels and deposited doses.Page 8-48, lines 7-9: Among the severe limitations of in vitro studies are the dose levelswhich are generally orders of magnitude higher than experienced in vivo; and in addition the factthat only acute effects and mechanisms can be evaluated in vitro which could be very differentfrom mechanisms causing chronic effects in vivo. These significant limitations should be addedonto the discussion in this section.The title of Chapter 8.5 refers only to in vitro exposures, which gives theimpression that mechanisms can only be evaluated by doing in vitro studies. This is not correct,mechanisms are also evaluated by in vivo studies, in fact, the in vivo studies may be moreimportant since they only can provide compelling evidence that any mechanistic pathwayexplored in vitro, indeed, is also operating under in vivo conditions which are obviously muchmore complex.Page 8-57, lines 30-31: This two-line summary can be used for any type of particle andis not very specific, and it may be useful here to also again point out that the high doses that areused in these in vitro studies need to be considered. A sentence stating that detailed specificmechanisms related to ambient PM still need to be uncovered should be included here.Page 8-65, line 8: What does the study of i.p. injection of ROFA contribute to anevaluation of mechanisms? This study doesn’t seem to make much sense.Lines 18-30: When comparing different dust materials in in vitro studies, itbecomes very difficult to rank the toxicity of the different dusts because it is not known as towhether the different particles are internalized by the cells to the same degree, and also thedosemetric in terms of mass vs. particle number or size can significantly influence the result.The term “exposure–dose” used in line 30 is not clear, what does it mean?Page 8-70, lines 15-16: This statement is only true if the chemical composition of theultrafine particle and larger particle is the same, which should be added here.Lines 15-29: Lines 27 – 29 provide an explanation for the observation that highdoses of fine particles cause a greater effect than high doses of instilled ultrafine particles.Indeed, results of our earlier study (Oberdörster et al., 1992) demonstrated that the significantamount of ultrafine particles being interstitialized when high doses are instilled causes a decreasein the inflammatory cells in the alveolar space compared to inflammatory cell influx at lowerdoses of instilled ultrafine particles.Line 31: The studies by Oberdörster et al. (2000), which are alluded to here, inA - 69