Contribution of Dental Amalgam to Urinary Mercury Excretion in Children
Environ Health Perspect. doi:10.1289/ehp.11013 available via http://dx.doi.org [Online 15 February 2008]
Referencing: The Contribution of Dental Amalgam to Urinary Mercury Excretion in Children
Woods et al. (2007) studied a group of children (n = 507) who were exposed by inhalation to elemental mercury (Hg0) from dental amalgam fillings. In the study, 253 subjects were exposed, whereas the remaining 254 children, the control group, were exposed to composite resin. We consider the experimental design of their study to be adequate, but we do have questions about their methods of data handling and interpretation.
For example, we do not understand why instead of always using creatinine-adjusted Hg levels, they used—in some instances—unadjusted Hg levels. In fact, there is continuous alternation and exchange between the two biological concepts (i.e., between the unadjusted and the adjusted concentrations). There are at least three well-grounded and well-known reasons that creatinine adjustment is essential: a) urinary creatinine accounts for variations in 24-hr excretion (Aito et al. 1983); b) urinary creatinine adjustment reportedly reflects Hg blood levels (Smith et al. 1970) and possibly Hg body burden; and c) in the light of established knowledge, Hg blood levels reflect recent exposure (Piotrowski et al. 1975).
Accordingly, the lack of significance between the Hg levels (not adjusted for creatinine) of the amalgam and the control subgroups at year 7, the final year of the study by Woods et al. (2007), is probably a bias that is indicated by the disappearance of overlapping if creatinine adjustment had been performed, as suggested by Aitio et al. (1983) as long as 25 years ago. Also, because no adjusted data were reported for male and female levels, the impact of such an adjustment cannot be conjectured by the reader. Subsequently this prevents accurate evaluation of the Hg level trend over the years.
It should be pointed out that the data of Woods et al. (2007) do not allow us to extrapolate whether or not the exposed subgroup is in the steady state, because this condition depends on the time lag between urine collection and the last amalgam treatment(s). This limitation prevents an accurate interpretation of the decrease in urinary Hg levels over years.
Geller (1976) reported that Hg sulfide can coat Hg0, thereby slowing down the release of Hg vapor. Although no specific study has determined whether this is true for amalgams, we cannot exclude that Hg oxidation may yield Hg sulfide on the amalgam surface. Woods et al. (2007) speculated about the decrease in Hg urinary excretion over years, but they did not consider the possibility of sulfide formation. Moreover, they did not explain the decrease in Hg levels over time after year 2 but simply stated that "the rate of urinary [Hg] excretion exceeds the rate of [Hg] exposure from dental amalgam." The formation of a thin film of Hg sulfide on amalgam surfaces could be an explanation, especially since the Hg body burden—and consequently Hg urinary levels—may be either in the steady state or at an increasing elimination rate because of the addition of new fillings.
Furthermore, we feel that the use of the term "dose–effect relationship" by Woods et al. (2007) is questionable. Also, it is not clear if the term "dose" refers to the number of additional amalgam fillings over the years or to the difference between means. Also, "effect" has a completely different meaning in toxicology. In this case, another term should be used to more accurately indicate the difference in two urinary Hg levels. In our opinion, "differential dose minus follow-up years" would be more appropriate in the text than "dose effect."
Woods et al. (2007) stated that in children who received "up to 9 initial amalgam fillings, urinary Hg returned to pretreatment value within one year," but this statement is not clear because this trend applies only to children who received 0–4 amalgam fillings at baseline but not to the group that received 5–9 [Figure 4; Woods et al. (2007)].
Finally, Woods et al. (2007) omitted error bars from their Figure 4; SE or SD could have been easily calculated by the theory of error propagation and would probably have addressed the discussion more accurately, or at least would have tempered some conclusions, especially with regard to confirmation of the "whole-body biological half-time of Hg on the order of 60–70 days." This half-time is correct but there is a large margin of uncertainty based on the experimental data.
In conclusion, although Woods et al. (2007) used a well-structured experimental design, their conclusions are not accurate because of their handling of the experimental results and their use of basic toxicology terminology.
The authors declare they have no competing financial interests.
Ivo Iavicoli
Giovanni Carelli
Institute of Occupational Medicine
Catholic University of Sacred Heart,
Roma, Italy
E-mail: gcarelli@rm.unicatt.it
References
Aitio A, Valkonen S, Kivistö H, Yrjänheikki E. 1983. Effect of occupational mercury exposure on plasma lysosomal hydrolase. Int Arch Occup Environ Health 53:139–147.
Geller SA. 1976. Subacute and chronic tissue reaction to metallic mercury: two cases and a review of the literature. Mt Sinai J Med 43:534–541.
Piotrowski JK, Trojanowska B, Mogilnicka EM. 1975. Excretion kinetics and variability of urinary mercury in workers exposed to mercury vapour. Int Arch Occup Environ Health 35:245–246.
Smith RG, Vorwald AJ, Patil LS, Mooney TF Jr. 1970. Effects of exposure to mercury in the manufacture of chlorine. Am Ind Hyg Assoc J 31:687–700.
Woods JS, Martin MD, Leroux BG, DeRouen TA, Leitão JG, Bernardo MF, et al. 2007. The contribution of dental amalgam to urinary mercury excretion. Environ Health Perspect 115:1527–1531.
Contribution of Dental Amalgam to Urinary Mercury Excretion in Children: Woods et al. Respond
Environ Health Perspect. doi:10.1289/ehp.11013R available via http://dx.doi.org [Online 15 February 2008]
We are pleased to respond to Iavicoli and Carelli's comments on our article (Woods et al. 2007).
Iavicoli and Carelli question our use of creatinine adjustment; in previous studies, we addressed the pros and cons of this issue in depth (Heyer et al. 2007; Martin et al. 1996; Woods et al. 1998). In terms of the present study (Woods et al. 2007), instead of advocating one approach over the other, we presented data, where appropriate (e.g., Figure 2), as both adjusted and unadjusted measures to provide the reader access to both sets of results. Iavicoli and Carelli note only a slight difference in Figure 2 between comparisons of adjusted and unadjusted urinary Hg levels at year 7; in our article we explained the higher variability (not bias) in the unadjusted values. Because creatinine adjustment did not otherwise alter the urinary Hg findings in the study, as stated in our Figure 3 (Woods et al. 2007), we did not present adjusted values for data described in Figures 3 or 4. Iavicoli and Carelli's comments about blood Hg levels are not relevant because we did not measure blood Hg concentrations in this study.
Regarding Iavicoli and Carelli's comment on "steady state," data presented in our Figure 4 (Woods et al. 2007) allow the reader to discern the influence of additional amalgam treatment on Hg body burden over time, as inferred from annual urinary Hg levels. A comprehensive pharmacokinetic evaluation of Hg body burden was neither intended nor within the scope of this study.
Iavicoli and Carelli speculate that Hg sulfide on teeth surfaces might have affected observed changes in urinary Hg levels; however, others (Brune 1986; Brune and Evje 1985; Gebel and Dunkelberg 1996) have clearly shown that sulfide (and other oxidation) layers are continuously removed by the effects of mastication, as well as by hot foods and liquids. These layers do regenerate but are in a constant state of flux. Because all of the amalgam used in this study (Woods et al. 2007) was of a single formulation, there would have been no variation in the tendency to form sulfide layers from amalgam treatment. Additionally, although there may have been some variation in oral pH among study subjects that could have influenced this process, Hg elimination still occurs at a relatively constant state. Therefore, we do not consider Hg sulfide film formation to be a significant factor in urinary Hg excretion over time.
Iavicoli and Carelli question our use of "dose effect" to describe the relationship of amount of amalgam treatment received with urinary Hg concentration. However, we consider this depiction appropriate.
Finally, Iavicoli and Carelli point out that the trend that children who received up to nine initial amalgam fillings but no subsequent treatment returned to pretreatment values within 1 year is not clear. This statement should have been "within 1 additional year" (i.e., by year 3 of follow-up). Urinary Hg levels were highest approximately 2 years after initial amalgam treatment for those with no subsequent treatment; those with ≥ 10 fillings at initial treatment and no subsequent treatment took > 3 years (approximately 5 years) to return to pretreatment levels. For Figure 4 (Woods et al. 2007), we obtained confidence intervals, but they were not included because of the clutter they created in the figures. Thus, the statements refer to trends and not statistical significance.
The authors declare they have no competing financial interests.
James S. Woods
Department of Environmental and Occupational Health Sciences
University of Washington
Seattle, Washington
jwoods@u.washington.edu
Michael D. Martin
Department of Oral Medicine
University of Washington
Seattle, Washington
Timothy A. DeRouen
Department of Dental Public Health Sciences
University of Washington
Seattle, Washington
References
Brune D. 1986. Metal release from dental biomaterials. Biomaterials 7:163–175.
Brune D, Evje DM. 1985. Man's mercury loading from a dental amalgam. Sci Total Environ 44: 51–63.
Gebel T, Dunkelberg H. 1996. Influence of chewing gum consumption and dental contact of amalgam fillings to different metal restorations on urine mercury content. Zentralbl Hyg Umweltmed 199:69–75.
Heyer NJ, Bittner AC Jr, Echeverria D, Woods JS. 2007. Response to comment on: "A cascade analysis of the interaction of mercury and coproporphyrinogen oxidase (CPOX) polymorphism on the heme biosynthetic pathway and porphyrin production" by Heyer et al. Toxicol Lett 2006; 161:156–166. Toxicol Lett 169:93–94.
Martin MD, McCann T, Naleway C, Woods JS, Leroux BG, Bollen MA. 1996. The validity of spot urine samples for low level occupational mercury exposure assessment and relationship to porphryin and creatinine excretion rates. J Pharmacol Exp Ther 277:239–244.
Woods JS, Martin MD, Leroux BG. 1998. Validity of spot urine samples as a surrogate measure of 24-hour porphyrin excretion rates. Evaluation of diurnal variations in porphyrin, mercury, and creatinine concentrations among subjects with very low occupational mercury exposure. J Occup Environ Med 40:1090–1101.
Woods JS, Martin MD, Leroux BG, DeRouen TA, Bernardo MF, Luis HS, et al. 2007. The contribution of dental amalgam to urinary mercury excretion in children. Environ Health Perspect 115:1527–1531.
