Attorney Jim Love of the IAOMT
Jim Love of the IAOMT explains why the Fawer Study is not Appropriate for RfC or MRL Derivation in the FDA's 2009 amalgam rule.
In its Final Rule on amalgam in 2009, the FDA relied on a 1995 EPA risk assessment for mercury, which relied principally on a study by Fawer, et al., in establishing a reference concentration of 0.3 µgs/m?. EPA's reliance on Fawer was criticized by the Petitioners because Fawer studied workers at a chlor-alkali plant.
Dr. Richardson criticized EPA's reliance on Fawer, et al., on the basis that the presence of chlorine gas reacted with mercury vapor. The resulting mercuric-chloride did not absorb as well as mercury vapor and did not have the same pharmacokinetics. FDA asked its Committee whether the exposure-response relationship for mercury vapor was modified by concomitant exposure to both mercury vapor and chlorine gas.
Dr. Griffin of the EPA argued that the issue wasn't worthy of consideration because 250 subjects were considered in the course of three studies, not one, and only 12 of the 250 workers were chlor-alkali workers. The balance of the subjects were dentists and fluorescent lamp workers who were not exposed to chlorine gas.
Dr. Richardson, who had already spoken to the Committee, was not allowed to address this comment, but he later communicated his objection to Michael Adjodha of the FDA.
Dr. Richardson's comments are set forth below:
I was not given the opportunity to challenge the panelist from EPA, nor rebut the claim that my (and co-authors) concern for confounding by chlorine gas exposure in chloralkali workers was a "red herring". Her claim of "only 12" chloralkali workers in the Fawer, et al study is correct, but this was 12 of only 26 workers studied, or 46% of the exposed cohort. This is not an insignificant proportion of those studied.
Dr. Richardson further noted:
EPA's IRIS summary reflects EPA's reliance on studies by Piikivi and Tolonen (1989; 41 chloralkali workers) and Piikivi and Hanninen (1989; 60 chloralkali workers), and Piikivi (1989; 41 chloralkali workers). The studies of Ngim, et al. in 98 dentists, and Liang, et al. in 88 fluorescent lamp factory workers were referenced as "corroborative studies" only, which "bracketed" the exposures within the other studies.
Dr. Richardson concluded:
Assuming that Ngim, et al. and Liang, et al. cohorts are added into the total studied cohorts, the total persons exposed = 354, of which 154 (43.5%) are from chloralkali plants. Again, this is not an insignificant proportion, nor is concern for confounding by chlorine gas exposure a "red herring".
Further, if Ngim, et al. and Liang, et al. are only corroborative studies (noted in the IRIS summary as "bracketing" the exposure range of the other studies), then they don't count in the total, and the total exposed considered for RfC development was 168, of which 154 (91.7%) exposed workers were chloralkali workers.
Of all of the reported average Hg levels in air for the various exposed groups, the Ngim, et al. study reported the lowest time weighted average air concentration (the lowest LOAEL; 14 µgs /m3) associated with effects, of any of the studies.
So, it appears that the most sensitive study (effects at lowest level) was ignored; it may also indicate that co-exposure to chlorine gas increased the LOAEL (decreased sensitivity in workers) by 85% (raising the LOAEL from 14 to 26 ug/ m3); again, no red herring.
Therefore:
- reliance on Fawer, et al. has 46% of exposed persons from chloralkali industry;
- reliance on all studies has 43.5% chloralkali workers;
- if Ngim, et al. and Liang, et al. are "corroborative" only (i.e., used for comparison but not for direct calculation of REL), then 91.7% of exposed group were chloralkali workers.
- reliance on Fawer, et al. and others as per USEPA also ignored the lowest measured LOAEL.
In preparing his 2009 risk assessment for mercury, Dr. Richardson relied on Ngim, et al., which did not rely on the study of workers from the chloralkali industry. The paper also represented the lowest reported LOAEL. Dr. Griffin stated that the goal of REL development was to identify the study that had critical effects at the lowest level; and that basing the RfC on this 'most sensitive study' helps protect against effects observed at higher levels.
So, Dr. Richardson's concern for use of chloralkali workers was not a red herring. In fact, the Ngim, et al. study reported the lowest LOAEL of the studies relied on by EPA, and has no confounding interference by concomitant chlorine gas exposure. Neither Dr. Griffin nor FDA has since commented on Dr. Richardson's criticisms. As we stated in our Petition, reliance on Fawer, et al. is misplaced.
Dr. Ismail supported the view of the Petitioners that the literature needed to be updated between 1992 and 2010, and that it was inappropriate to rely on a 1995 EPA RfC while ignoring the many years of published research during this period. [494] Dr. Bates agreed with Dr. Ismail. [495]
MERCURY EXPOSURE HAS TRIED TO CONTACT DR GRIFFIN FOR COMMENT (7/20/2011), BUT SHE HAS NOT RESPONDED AT THE TIME OF THIS POSTING.
