Methylmercury neurotoxicity independent of PCB exposure.

It is unclear whether the SDA long-term morbidity results (10) are coherent with mortality results. Among individuals who were symptom-free at the start of the study, there was an association between increased symptoms and PM. These risk estimates were 40-fold greater than those estimated for smoking. There were no analyses presented for those individuals who had symptoms at the start of the study, but became symptom-free at the end of the study. This analysis is just as important as the analysis of incidence of new symptoms. If both showed an association with PM, the results would not be internally coherent (1). I presented evidence showing why reduced lung function could be a confounder in these studies and that it meets the criteria for confounding. First, reduced lung function must be a risk factor for increased mortality (1). Second, reduced lung function must be correlated with between-city variations in PM2.5, although the relationship shown in Figure 3 (1) could only be tested with the ecologically based exposure measures used in that study. Third, reduced lung function should not be on the same causal pathway as PM2 5 for mortality; the point of the example shown in Figure 4 (1) was to suggest that important differences occur in the distribution of risk factors between cities, with lung function being one of many possible risk factors. I do not believe that adjustment for a few individual-level risk factors has adequately addressed the complex overall potential for confounding in these studies. We all realize that we can never make all groups completely comparable, but between-city differences in PM2 5 concentrations are so small and relative risks so low that these studies are particularly susceptible to even slightly confounded results. I believe this paper (1) and the questions raised by Kuinzli and Tager are in line with the scientific process of verification and refutation. They have led to further discussion that will hopefully lead to additional testing. However, it is disappointing that Kunzli and Tager chose to question the integrity of the author's motivation based on affiliation. Judgment on whether or not my critique clouds the complex issues around PM2.5 and mortality should be determined not by my affiliation but solely on the scientific merits of the argument. I thank John Bukowski, Wendy Huebner, Mark Nicolich, and Rob Schnatter for their stimulating discussions and input.