[{"@context":"https:\/\/schema.org\/","@type":"Article","@id":"https:\/\/iaomt.org\/fda-evidence-for-safety-of-amalgams-appendix-viii\/#Article","mainEntityOfPage":"https:\/\/iaomt.org\/fda-evidence-for-safety-of-amalgams-appendix-viii\/","headline":"FDA Evidence for Safety of Amalgams – Appendix VIII","name":"FDA Evidence for Safety of Amalgams – Appendix VIII","description":"The Casa Pia Children’s Amalgam Trial The FDA’s Evidence that amalgam exposure does not affect long-term health outcomes Woods, J.S. et al., \u201cBiomarkers of Kidney Integrity in Children and Adolescents with Dental Amalgam Mercury Exposure: Findings from the Casa Pia Children\u2019s Amalgam Trial,\u201d\u00a0Environmental Research, Vol. 108, pp. 393-399, 2008. The FDA is STILL using the  [...]","datePublished":"2025-08-11","dateModified":"2025-08-11","author":{"@type":"Person","@id":"https:\/\/iaomt.org\/author\/moore\/#Person","name":"International Academy of Oral Medicine & Toxicology","url":"https:\/\/iaomt.org\/author\/moore\/","identifier":1240,"image":{"@type":"ImageObject","@id":"https:\/\/iaomt.org\/wp-content\/litespeed\/avatar\/bfc92e3fae46f1c852ba2a2990470c47.jpg?ver=1776187415","url":"https:\/\/iaomt.org\/wp-content\/litespeed\/avatar\/bfc92e3fae46f1c852ba2a2990470c47.jpg?ver=1776187415","height":96,"width":96}},"publisher":{"@type":"Organization","name":"The International Academy of Oral Medicine & Toxicology","logo":{"@type":"ImageObject","@id":"https:\/\/iaomt.org\/wp-content\/uploads\/IAOMT-Schema-app-logo.jpg","url":"https:\/\/iaomt.org\/wp-content\/uploads\/IAOMT-Schema-app-logo.jpg","width":120,"height":60}},"image":{"@type":"ImageObject","@id":"https:\/\/iaomt.org\/wp-content\/uploads\/iaomt-logo2.jpg","url":"https:\/\/iaomt.org\/wp-content\/uploads\/iaomt-logo2.jpg","width":100,"height":100},"url":"https:\/\/iaomt.org\/fda-evidence-for-safety-of-amalgams-appendix-viii\/","about":["Articles"],"wordCount":1403,"keywords":["Dental Mercury Regulatory"],"articleBody":"The Casa Pia Children’s Amalgam TrialThe FDA’s Evidence that amalgam exposure does not affect long-term health outcomesWoods, J.S. et al., \u201cBiomarkers of Kidney Integrity in Children and Adolescents with Dental Amalgam Mercury Exposure: Findings from the Casa Pia Children\u2019s Amalgam Trial,\u201d\u00a0Environmental Research, Vol. 108, pp. 393-399, 2008.The FDA is STILL using the above-referenced study, and others, on their website (hyperlinked above) and in the Special Controls document[1] to tout the safety of Amalgam fillings, despite new data to refute or reduce the impact of the initial study findings. The data for this, and prior and subsequent studies came from the Casa Pia trial in which urinary porphyrin data, sensitive indicators of mercury exposure, were acquired but not examined in initial reports.In this trial, increases in urine mercury younger children were observed (8\u20139 years) during peak exposure at years 2\u20133*, suggesting potential subclinical renal impact[2]. Third, they identified strong sex differences in urinary mercury. The FDA chose to ignore these findings.*In the trial urinary mercury (U-Hg) peaked at ~3.2\u202f\u00b5g\/L in year 2 and then declined to baseline by year 7 (despite acquiring more amalgam fillings) – likely reflecting excretory limitations rather than reduced exposure, potentially underestimating internal body burden.[3]In a New England trial, microalbuminuria (a marker of subtle kidney dysfunction) was significantly more frequent in the amalgam group during years 3\u20135 (OR ~1.8), including persistent cases, calling into question the claim of \u201cno organ-level effect.\u201d[4]Even large cohorts (n \u2248\u202f500) may lack sensitivity to detect subtle neurocognitive or renal effects, especially when using broad clinical tests rather than specialized neurotoxicological endpoints.[5] Critics have suggested that continuous measures (e.g., nerve conduction, attention tasks) or genetically susceptible subpopulations (e.g., metallothionein polymorphisms) were not adequately examined.These two points are crucial: Reviewers criticize the selective presentation of endpoints, notably porphyrin data, (which was collected but not presented), and the exclusion of genetically or clinically vulnerable children, which biases conclusions toward safety.Critique AreaSpecific ConcernBiomarkersMissing subtle renal\/neurotoxic signals in urinary porphyrinsExposure metricsDeclining U-Hg levels reflect excretion limits, not true exposureRenal effectsMicroalbuminuria suggests mild kidney stress\/damageStatistical sensitivityStudy may be underpowered for small effect sizesEndpoint selectionCoarse tests may overlook nuanced neurotoxicity or susceptible subgroupsThe above-listed findings highlight that while Lauterbach et\u202fal. concluded no neurological harm, valid concerns remain regarding subtle renal effects, limitations in exposure measurement, and the potential for overlooked neurotoxic impacts in sensitive subgroups. Comprehensive follow-up studies with targeted biomarkers and sensitive testing are still warranted.[6] Additionally, the amount of exposure was not accounted for – regardless of exposure to amalgam, all amalgam-bearers were lumped together. This is another crucial point. Additional Follow up StudiesGenetic Polymorphisms & Increased VulnerabilityModification of neurobehavioral effects of mercury by genetic polymorphisms of metallothionein in childrenChildren (aged 8\u201312) from the original Casa Pia trial were genotyped for two metallothionein variants (MT1M rs2270837 and MT2A rs10636). Among boys, specific alleles of MT1M and MT2A showed significant interactions with urinary mercury exposure, correlating with worse performance across multiple neurobehavioral domains (memory, attention, etc.). No such effect was observed in girls indicating that genetically susceptible subgroups, particularly boys with certain MT variants, can and do experience adverse effects even when average results appear safe.[7]Extended Neurological & Renal Follow-UpBellinger et al. (New England Children\u2019s Amalgam Trial – NECAT)Children were followed up for 5 years, assessing IQ, memory, visuomotor skills, attention, and executive function. No average group differences between amalgam vs composite groups; however, the study acknowledged the possibility of subtle or delayed effects not captured.[8] Further, all amalgam-bearers were placed in one group, regardless of exposure level – no correlational analyses were performed. Reanalysis by Geier and Geier 2012 of the Casa Pia trial, found a significant dose-dependent relationship between mercury exposure from dental amalgams and urinary mercury levels.[9]Continued Porphyrin & Mercury Biomarker AnalysisAnother reanalysis of the Casa Pia dataset, conducted by Geier et al. (2012) examined urinary mercury and porphyrin profiles in detail. Porphyrins are molecules in the pathway that produce heme. Heme plays several roles in the human body, one of which is as a component of hemoglobin, the molecule that delivers oxygen to our cells. There are several stages in the pathway, and therefore several different porphyrins. Mercury, and only mercury, inhibits the production of the final 3 porphyrins. Mercury exposure was compared to all stages of the porphyrin pathway. A direct relationship was shown, such that exposure to mercury through amalgam fillings resulted in significant reductions in the last 3 porphyrins.Thus, when the same data are analyzed appropriately, using dose-dependent measures, rather than grouping subjects as amalgam-bearers vs not, the data confirm that greater exposure to amalgam fillings (i.e., size, number and length of time of exposure) increase urinary mercury AND decrease the efficiency of heme production, a basic function of the human body. The FDA continue to deny this – but simple common sense and a reading of the literature, including the letter that must have been written in futility by the authors of the early Casa Pia Trial papers,[10] refuting the Geier and Geier science, clearly show that even a relatively short exposure (8 years) to mercury from amalgam fillings cause disruption of cell function and therefore, mercury amalgam fillings can only be classified as unsafe. One must wonder how DeRouen and Lauterbach sleep at night knowing that deeper dives into the data such as dose-response analyses are crucial to unveiling effects. Why do they insist on grouping all amalgam-bearers into one category, muddying the data? Any decent epidemiologist knows the flaws of conducting science in such a way.FocusFindingsGenetic susceptibilityMT variants linked to adverse neurobehavioral outcomes in boys (pubmed.ncbi.nlm.nih.gov)Sample stratificationEffects may be masked when genetic variability is not consideredRenal\/biomarkersUrinary mercury and porphyrin profiles reflect dose\u2013response heterogeneityLong-term exposureMercury excretion dynamics change over time, suggesting tissue effects need further studyBroader Evidence of Genetic InteractionsAn FDA white paper (2021) reviews several studies showing: Polymorphisms in BDNF, CPOX4, and MT genes can significantly affect neurobehavioral and psychomotor outcomes in dental professionals exposed to low-level mercury.[11]Casa Pia and NECAT studies both showed urinary mercury peaked around 2\u20134 years post-amalgam placement, even when new amalgams were placed, and then declined, likely due to changing excretion dynamics, not reduced exposure.[12][1] Center for Devices and Radiological Health, \u201cDental Amalgam, Mercury, and Amalgam Alloy – Class II Special Controls Guidance for Industry and FDA Staff,\u201d FDA, FDA, March 23, 2021, https:\/\/www.fda.gov\/medical-devices\/guidance-documents-medical-devices-and-radiation-emitting-products\/dental-amalgam-mercury-and-amalgam-alloy-class-ii-special-controls-guidance-industry-and-fda-staff.[2] Xibiao Ye et al., \u201cNephrotoxicity, Neurotoxicity, and Mercury Exposure among Children with and without Dental Amalgam Fillings,\u201d International Journal of Hygiene and Environmental Health 212, no. 4 (2009): 10.1016\/j.ijheh.2008.09.004, https:\/\/doi.org\/10.1016\/j.ijheh.2008.09.004.[3] James S. Woods et al., \u201cThe Contribution of Dental Amalgam to Urinary Mercury Excretion in Children,\u201d Environmental Health Perspectives 115, no. 10 (2007): 1527\u201331, https:\/\/doi.org\/10.1289\/ehp.10249.[4] Lars Barregard et al., \u201cRenal Effects of Dental Amalgam in Children: The New England Children\u2019s Amalgam Trial,\u201d Environmental Health Perspectives 116, no. 3 (2008): 394\u201399, https:\/\/doi.org\/10.1289\/ehp.10504.[5] Gene E. Watson et al., \u201cNeurodevelopmental Outcomes at 5 Years in Children Exposed Prenatally to Maternal Dental Amalgam: The Seychelles Child Development Nutrition Study,\u201d Neurotoxicology and Teratology 39 (2013): 57\u201362, https:\/\/doi.org\/10.1016\/j.ntt.2013.07.003.[6] Martin Lauterbach et al., \u201cNeurological Outcomes in Children with and without Amalgam-Related Mercury Exposure: Seven Years of Longitudinal Observations in a Randomized Trial,\u201d Journal of the American Dental Association (1939) 139, no. 2 (2008): 138\u201345, https:\/\/doi.org\/10.14219\/jada.archive.2008.0128.[7] James S. Woods et al., \u201cModification of Neurobehavioral Effects of Mercury by Genetic Polymorphisms of Metallothionein in Children,\u201d Neurotoxicology and Teratology 39 (2013): 36\u201344, https:\/\/doi.org\/10.1016\/j.ntt.2013.06.004.[8] D. C. Bellinger et al., \u201cA Dose-Effect Analysis of Children\u2019s Exposure to Dental Amalgam and Neuropsychological Function: The New England Children\u2019s Amalgam Trial,\u201d J Am Dent Assoc 138 (September 2007): 1210\u201316.[9] DA Geier et al., \u201cA Dose-Dependent Relationship between Mercury Exposure from Dental Amalgams and Urinary Mercury Levels: A Further Assessment of the Casa Pia Children\u2019s Dental Amalgam Trial,\u201d Human & Experimental Toxicology 31, no. 1 (2012): 11\u201317, https:\/\/doi.org\/10.1177\/0960327111417264.[10] TA DeRouen et al., \u201cCritique of Reanalysis of Casa Pia Data on Associations of Porphyrins and Glutathione-S-Transferases with Dental Amalgam Exposure,\u201d Human & Experimental Toxicology 34, no. 3 (2015): 330\u201332, https:\/\/doi.org\/10.1177\/0960327114542885.[11] Food and Drug Administration, \u201cWhite Paper: FDA Update\/Review of Potential Adverse Health Risks Associated with Exposure to Mercury in Dental Amalgam,\u201d FDA, FDA, January 30, 2025, https:\/\/www.fda.gov\/medical-devices\/dental-amalgam-fillings\/white-paper-fda-updatereview-potential-adverse-health-risks-associated-exposure-mercury-dental.[12] Woods et al., \u201cThe Contribution of Dental Amalgam to Urinary Mercury Excretion in Children.\u201d"},{"@context":"https:\/\/schema.org\/","@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"name":"FDA Evidence for Safety of Amalgams – Appendix VIII","item":"https:\/\/iaomt.org\/fda-evidence-for-safety-of-amalgams-appendix-viii\/#breadcrumbitem"}]}]