(CASAC) Peer Review of EPA's Integrated Science Assessment

Figure 3-1, Page 3-12: This is an important figure that should be more thoroughlydiscussed. The figure indicates, from one of the larger early studies that there are markeddiscrepancies in the responsiveness of individual subjects. About 25% of the subjectswere essentially unresponsive in terms of airway sensitivity below 2 ppm and another25% were responsive below 0.5 ppm. Thus, in assessing group data it is obviously thecase that within any group the responders and the non-responders need to be consideredseparately if at all possible. In this study of asthmatics, in which the presumption wouldbe that the response pattern would be random across the group, this clearly was not thecase. I am sure that I and others argued in the past that this raises concern that inattempting to justify a short term standard the fact that which 25% of the asthmaticpopulation would be affected cannot be determined prior to exposure argues forconsideration in the setting of a standard with an adequate margin of safety. I wouldcontend that 25% of the population of asthmatics is a larger fraction of the most sensitivepopulation than one should be comfortable to ignore in setting a short term standard.This argument did not win the day in 1994. The data since that time has furtherestablished the issue that there are what might be called “super sensitive” groups ofpeople and the whole issue of both what proportion of the population should be protectedand what the margin of safety should be will need to be revisited. In this case margin ofsafety is not a surrogate for uncertainty of effect but a measure of the size of thepopulation to be protected.In reaching a conclusion on page 3-46 the general impression is that the evidenced issuggestive. However, not taken into account in reaching these conclusions is theevidence that not all subjects within any given population are equally sensitive to theimpact of SO2. In my mind this phenomena tips the balance that regulation of short termexposure is necessary.This point is made even more effectively in Section 4.1.1 on page 4.2-3 along with figure4-1. Given that sRaw is measured as doubling and FEV1 change is measured as 15%decrease the range of changes from 0.2ppm to 0.6 is quite substantial and is consistentwith a significant adverse effect that will need to be modeled in the risk assessment.A better job needs to be done in indicating that subgroups of subjects appear to be moresensitive and may be driving the overall assessments in any specific study. Thesesubgroups appear to exceed 5% to 13% for sRaw and FEV respectively, at the lowestlevels of exposure tested (0.2 ppm). The lack of a threshold at these (relatively) highlevels of exposure as compared to “background of less than 15ppb makes straightforwardextrapolation uncertain. I am sure there are people who are sensitive at these lower levelsbut finding an appropriate level and population at risk will be difficult.With regard to long term exposure and mortality the larger (and better) conducted USstudies are consistent but when assessed in the context of all studies that might beinterpreted as negative leave the impression that the results are inconsistent and thereforeno prudent declaration of causal association can be made. This seems slightly off base asthere is adequate reasoning given as to why some studies might be positive and somenegative and one simply cannot sum the total of studies.45