Background mercury air concentration ohio

Neurobehavioral effects of dental amalgam in children: a randomized clinical trial. A prospective study with a relatively large sample size of children living in Lisbon, Portugal, aged 8 to 10 years at the start of the study and who had no prior restorations. The m ean number of surfaces restored was Follow-up lasted for 7 years. Hg levels in the urine were only minimally increased 0. This is far less than the more than the 1.

Subscribe to our newsletter

The peak mercury levels reached in the amalgam group were more than fold less than the lowest urine levels that have been reported as threshold for effects on vision and motor tremor, which are some of the neurological functions most sensitive to disruption by Hg Urban et al. Functional domains assessed included memory, attention, and visuomotor and nerve conduction velocities.

Assessments were performed approximately on an annual basis. IQ was assessed at the beginning and the end of the study. Weaknesses: earliest age was years at start; only 7 years of follow up. Factor-Litvak et al. Mercury derived from dental amalgams and neuropsychologic function. Dose-response data were examined for the number of amalgams vs. Exposure level correlations were examined by stratifying groups into 0; ; ; ; and total amalgam surfaces.

The data showed that urinary Hg levels increase with increasing amalgam surfaces for each 10 surfaces the urine Hg levels went up between 0. There was no evidence that dental amalgams produced neurotoxicity. Strengths: humans; long-term exposures; relevant endpoints; good n and power; attempt to correlate exposure level with effect dose-response: no association. Weaknesses: cross-sectional study; absence of data on when amalgams were actually placed, removed or replaced, but suspect exposures of years.

Hujoel et al. Mercury exposure from dental filling placement during pregnancy and low birth weight risk. This study reported Hg exposure as number of amalgam fillings note that this was not number of surfaces. Data were stratified into 0, or fillings for dose-response analyses concerning low birth weight. There was no significant association with dose of inorganic Hg number of amalgam fillings and low birth weight. Strengths: human subjects, large n; case-control study.

Weaknesses: no urine Hg levels. Kingman et al. Amalgam exposure and neurological function. Urine Hg levels were not given in this study but can be inferred through the earlier Kingman et al. Significant but marginal effects were observed on continuous vibrotactile response, but only in select groups i. There was no dose-response in the findings.

Strengths: humans subjects; amalgam exposures; large n. Weaknesses: lack of continuous variables i. Regional brain levels of Hg were determined at autopsy in 68 subjects with AD and in 33 controls. Regional Hg levels in the brain did not correlate with the number of amalgams and there were no differences between the AD and the control group with respect to number of amalgams. The authors concluded that the Hg levels were not elevated in persons with AD and that the number of amalgams could not be shown likely to affect the incidence of AD. Weaknesses: even with relatively high numbers for a tissue analysis study, the number of subjects was low.

Summary of human amalgam exposures and outcomes. Collectively, these studies provide some of the most important and relevant new observations concerning the possibility that mercury amalgam might result in adverse human health effects in persons with amalgam restorations. The two clinical trials in children also provide data for a very important sensitive subpopulation. The large retrospective studies have large sample sizes. Considering all of the studies, the data do not support adverse effects of mercury amalgam in the groups evaluated.

In those studies where a significant association was noted i. For the MS observation, it was noted that the incidence of MS in the study population was well below that of the general population. In addition, there were significant Hg-related decreases in hazard ratios for several outcomes including kidney disorders, inflammatory responses and toxic neuropathy in the same study.

An additional cross-sectional study in adults found no correlation between urine Hg levels and a variety of endpoints assessing several levels of the neuraxis. In the study showing significant correlations between number of amalgam surfaces and decreased vibrotactile response, it was noteworthy that the effect was demonstrable only in select groups. In addition, there were no urine Hg data presented in that particular study, making both interpretation and dose-response analysis difficult; e. The two clinical trials in children found no correlations between amalgam placements and adverse effects even with extensive and repeated assessments of a multitude of neurobehavioral functions.

Thus, the weight of evidence from these studies that provide the most relevant data clearly do not support the hypothesis that exposure to mercury via dental amalgam restorations causes adverse biological outcomes. Five studies examined the ability of human genetic polymorphisms to alter biological responses to mercury exposure. This was a very comprehensive clinical study also discussed earlier under occupational exposures in dentists and dental assistants that reported the effects of a brain derived neurotrophic factor BDNF polymorphism Val66MET or Hg on motor activity and a variety of psychomotor functions e.

There were no significant effects of Hg or the BDNF polymorphism on verbal intelligence or reaction time. In this study, as in the previous work from this group, several quantitative measures of neural function were analyzed. The BDNF polymorphism was correlated with effects on 4 measures in the dentists and 3 measures in the assistants. Both the BDNF polymorphism and urine Hg levels correlated with scores on finger tapping in the dentists and hand steadiness and trail making in the dental assistants.

The authors suggest the possibility of additive effects between Hg exposure and the BDNF polymorphism for these measures, implying that persons with the BDNF polymorphism may be at greater risk of Hg effects. This is a follow-up clinical study in the same subjects dentists and dental assistants used in the Echeverria et al. In the present study, correlation of a CPOX4 polymorphism alteration in exon 4 of the gene encoding the coproporphyrinogen oxidase enzyme of the heme synthetic pathway or urine Hg levels with a host of neurological endpoints were analyzed. Significant correlations were found between urine Hg levels and 9 neurobehavioral measures in dentists digit span forward and backward; visual reproduction; symbol-digit; finger tapping dominant, non-dominant and alternate; hand steadiness; and tracking and 8 measures in assistants digit span forward; digit-symbol; pattern discrimination; trailmaking B; hand steadiness; finger tapping dominant, non-dominant and alternate; and vibration sensitivity.

In addition, the CPOX4 polymorphism alone was associated with 4 measures in dentists spatial span, pattern memory, symbol digit, vigilance and 5 in dental assistants digit span, visual reproduction, symbol digit, simple and choice Reaction Times. The authors suggest the possibility of additive effects between the CPOX4 polymorphism and Hg exposure which suggests that persons with the CPOX4 polymorphism may be at greater risk for Hg effects. The authors present their analysis of self-reported data obtained from questionnaires for evaluating a range of recent and chronic symptoms including mood, and physical and other mental status.

They observed 3 significant correlations between the BDNF polymorphism alone a p value of 0. Three measures in dentists 2 in the predicted direction and 13 in dental assistants 11 in the predicted direction were correlated with urine Hg levels only. Although it was suggested that persons with the BDNF polymorphism may be at greater risk from Hg exposure, there was only one outcome that correlated with both urinary Hg and the BDNF polymorphism in this study. Strengths: human subjects; large n; large number of relevant observations; genetic markers. Weaknesses: lack of non-dental worker controls; dental assistants were from the same clinics as dentists.

A cascade analysis of the interaction of mercury and coproporphyrinogen oxidase CPOX polymorphism on the heme biosynthetic pathway and porphyrin production. There were no non-dental worker controls and the number of years of exposure to amalgam were not reported here. The subjects are very likely a subset of those in other studies Echeverria et al. This work basically revisits earlier work Woods et al. However, there is no explanation of why this would be relevant to any blood disorders or other adverse effects.

This manuscript is clinically oriented but is more of a review article about remodeling and refining the ways in which Hg can interact with humans having the CPOX4 allele to affect products and intermediates in the heme biosynthetic pathway. Strengths: human subjects, relevant endpoints; genetic markers. Weaknesses: lack of non-dental worker controls could maximize population homogeneity; dental assistants were from the same clinics as dentists; both of these issues make it impossible to rule out workplace characteristics or exposures other than Hg that may have contributed to their findings; there is no discussion of an association of altered heme synthetic pathways and adverse biological effects.

Woods et al. The association between genetic polymorphisms of coproporphyrinogen oxidase and an atypical porphyrinogenic response to mercury exposure in humans. The number of amalgams is not reported in this study. Since there are no non-dental controls there could be another factor s that the dentists and dental assistants have in common other than Hg exposures to influence the findings.

Weaknesses: lack of non-dental worker controls; dental assistants were from the same clinics as dentists; no discussion of how altered heme synthetic pathways as reported here might lead to potential adverse effects. Summaries of studies that examined the relationship between human genetic polymorphisms and urine Hg levels to alter biological responses. All of the studies in this section were carried out in the same human subjects or subsets of the same populations. Thus, to varying degrees, they all share different strengths but the same weaknesses.

Portable Mercury Vapor Analyzer Light | USA | Ohio Lumex

These studies lacked the use of non-dental worker controls, thus the issue of selection bias arises. In addition, the dental assistants chosen as participants were from the same clinics as the participating dentists. There were often no associations between the outcomes of interest and any index of cumulative or past peak Hg exposures. These issues make it impossible to rule out workplace characteristics or exposures other than Hg that may have contributed to the findings from all of these papers.

Thus, interpretation of the data for those with dental amalgam restorations is more difficult. Given these deficiencies, it does appear that BDNF and CPOX polymorphisms are associated with alterations in important behavioral responses nervous system functions. Mercury vapor and female reproductive toxicity. Adult female rats were exposed nose only to Hg vapor over postnatal days PNDs There were no significant effects of Hg vapor exposure on pregnancy rate or number of implantation sites. Estrous cycles were slightly prolonged in the 2 higher dose groups, and progesterone and estradiol levels were significantly different in the high dose group.

Kidney Hg levels 0. Strengths: some dose-response information; inhalation of elemental mercury which is relevant to amalgam; nose-only exposures eliminates deposition on fur and subsequent ingestion; relevant endpoints. Weaknesses: rodent model; short-term exposures, urine samples were collected immediately after exposures so hr levels are not known; high doses maternal toxicity occurred at high doses.

Morgan et al. Deposition of inhaled mercury vapor in pregnant rats: maternal toxicity and effects on developmental outcome. Hg levels were measured in brain, liver and kidney in both exposed maternal animals and offspring and several other maternal tissues.

Hg levels increased in a dose-dependent manner in all tissues. No exposure-related histopathology was seen in lung, kidney or livers of pregnant animals when examined at several time points: gestational days 6 or 15 or postnatal day 1. Adverse effects on developmental outcome increased resorptions; decreased litter size and pup body weights occurred only at exposure levels that also caused maternal toxicity, i. Weaknesses: rodent model; short-term exposures, urine samples collected immediately after exposures so hr levels are not known; high doses maternal toxicity occurred at high doses.

Summary of animal studies that looked at issues of maternal and reproductive toxicity. Both studies indicate that there is no development toxicity associated with mercury vapor exposures that do not also cause maternal toxicity. Three studies were identified that examined the relationship between exposure to mercury vapor and behavioral outcomes. Evaluation of sensory evoked potentials in Long Evans rats gestationally exposed to mercury Hg 0 vapor. Offspring one male and female per litter were evaluated as adults between at postnatal days and Brain Hg levels were not reported for the animals in this study but these animals were given an exposure identical same lab to that reported to produce Hg levels of 0.

Those data showed that very little Hg crosses the placenta into the pups after maternal exposures. The neurological evaluations flash evoked potentials; pattern evoked potentials; compound nerve action potentials; cortical somatosensory evoked potentials; brainstem auditory evoked response; cerebellar somatosensory evoked potentials; nerve conduction velocity showed no conclusive effects on any measure tested; compound nerve potentials suggested a slight, but not significant, trend toward impairment.

The study concluded that there were no effects of prenatal Hg exposure on responses evoked from peripheral nerves or the somatosensory, auditory or visual modalities. Strengths: sampled a variety of levels of the neuraxis; mercury vapor was used; gestational exposure; assessed long-term residual effects in adulthood PND Weaknesses: rats; high dose exposure. Yoshida et al.

Elemental mercury exposure: An evidence-based consensus guideline for out-of-hospital management

Susceptibility of metallothionein-null mice to the behavioral alterations caused by exposure to mercury vapor at human-relevant concentration. This study utilized adult female mice with mutant metallothionein genes that are nonfunctional knocked out - KO versus animals with wild type metallothionein genes to look at how the metallothionein function affects the neurotoxicity produced by exposure to Hg vapor whole body immersion at 0.

At necropsy, the brain Hg levels in the metallothionein KO mice were 0. KO mice had a higher open field activity and poorer performance in passive avoidance test than the wild type mice. Hg toxicity and lower brain Hg levels were observed in KO mice compared to wild type mice.

Behavioral changes in metallothionein-null mice after the cessation of long-term, low-level exposure to mercury vapor. This study was an adult mouse study very similar to Yoshida et al. Evaluations for neurotoxicity occurred at the end of exposure and 12 weeks later and included locomotor activity open field behavior , learning ability passive avoidance , and spatial learning ability Morris water maze. After 29 weeks of exposure, metallothionein knock-out KO mice had brain Hg levels of 0. At the end of exposure, locomotor activity was marginally depressed in both strains, while 12 weeks later it was marginally increased in both strains.

Performance of the Morris water maze was not affected at any time point. The authors note their findings were the first to indicate that long-term, low-level Hg vapor can lead to persistent neurobehavioral effects.

Basic Information about Mercury

The effects reported did not follow the prediction that higher brain Hg levels are associated with greater neurological impairments. Summaries of studies that examined the relationship between exposure to mercury vapor and behavioral outcomes. The findings that lower brain Hg levels were associated with a greater degree of neurological deficit and the lack of concurrent controls in this study make the data difficult to interpret. The data from these studies do not provide information useful for addressing issues related to the effects of Hg vapor at the levels experienced by persons with amalgam restorations.

Consistent with previous reviews USPHS, ; ; ATSDR, of the literature, a positive association was observed between urinary mercury values and the number of amalgam fillings or surfaces placed Kingman et al, ; Factor-Litvak et al. It is clear that persons chronically exposed to mercury vapor in the workplace can suffer adverse health effects that often manifest as decrements in nervous system function. In some cases, recovery of function occurs after exposure has ended even though the process may take several years.

General cognitive function and intellectual capacity appears to be relatively unaffected in such cases. Occupational exposure of dentists and dental assistants to mercury vapor appears to increase Hg body burden that is not reflected in urine mercury levels. The data are not sufficient at present to conclude whether this increase in mercury body burden results in adverse neurobehavioral outcomes. Clinical trials in children have provided critical observations concerning the effects of exposure to mercury from dental amalgam.

Extensive, repeated assessments of a multitude of neurobehavioral functions demonstrated that there were no correlations between amalgam placements and adverse effects. Data from retrospective studies in large populations of adults do not support the finding of adverse effects of mercury amalgam and in a cross-sectional study there was no correlation between urine mercury levels and a variety of endpoints assessing several levels of the neuraxis.

Fetal levels of mercury are generally much less than maternal levels and decrease after birth even when exposure via breast milk continues. The weight of evidence from human clinical and epidemiological studies of mercury amalgam does not support the hypothesis that exposure to mercury via dental amalgam restorations causes adverse biological outcomes. Data from animal studies indicate that there is no developmental toxicity associated with mercury vapor exposures that do not also cause maternal toxicity. Gestational exposures to relatively high concentrations of mercury vapor did not result in any significant adverse effects on a variety of sophisticated electrophysiological outcomes in rat offspring when tested as adults.

Based on an evaluation of the extensive literature reviews conducted by ATSDR , and EPA , and an assessment of the health effects-based exposure reference values for elemental mercury derived by those agencies and WHO and ACGIH, no information was found that would change the comprehension of health risks for inorganic or elemental mercury and mercury in dental amalgam. Compared to previous analyses performed by USPHS, no significant new information was discovered from the review of these 34 articles that would change the risk estimates by FDA for the use of dental amalgam.

It is concluded that there is insufficient evidence to support an association between exposure to mercury from dental amalgams and adverse health effects in humans, including sensitive subpopulations. Neurotoxicology ; 26 3 Int J Epidemiol ; 33 4 J Am Med Assoc ; 15 Neurotox Teratol ; 20 4 Environ Hlth Perspec ; 10 : Toxicol Sci ; J Am Med Assoc ; 15 : Occup Environ Med ; 62 6 Neurotoxicol Teratol ; 27 6 Neurotoxicol Teratol ; 28 1 Occup Med ; 47 6 Neurotoxicol ; Environ Health Perspect ; 5 Toxicol Sci ; 82 1 Toxicol Sci ; 81 2 Tox Lett ; Am J Epidemiol ; 8 Toxicol Appl Pharmacol ; Neurotoxicology ; 26 2 J Dent Res ; 77 3 Neurotoxicol ; 21 4 Arch Gynecol Obstet ; 2 J Am Dent Assoc ; Environ Health Perspect ; 4 Neurotoxicology ; 24 1 Neurotoxicology ; 24 Sci Total Environ ; Vis Neurosci ; 21 3 Toxicol Appl Pharmacol ; 2 Toxicol Sci ; 80 1 Toxicol Lett ; 3 N Engl J Med ; 22 American Conference of Governmental Industrial Hygienists.

Cincinnati, Ohio. Environmental Protection Agency. March 29, Br J Ind Med ; Int Arch Occup Environ Hlth ; Roels H, Abdeladim S, Ceulemans E, Lauwerys R: Relationships between the concentrations of mercury in air and in blood and urine in workers exposed to mercury vapour. Ann Occup Hyg ; Public Health Service. January From the Working Group on Dental Amalgam.

outer-edge-design.com/components/facebook/1530-cell-tracker-reviews.php October World Health Organization. Based on Executive Summary Introduction II. Human Studies V. Animal Studies V.


  • command to find my ip address.
  • Learn more about Mercury Contamination.
  • Related Articles.
  • can i find an address from a phone number.
  • Mercury in the Nation's Streams?

Executive Summary Background Elemental mercury and inorganic mercury have been demonstrated for decades to be well-known toxicants in both laboratory animal and human epidemiological studies. Process The previous reviews of the scientific literature pertaining to health risk from mercury in dental amalgam conducted by U.

Conclusions The reviews of the scientific literature on mercury undertaken by ATSDR and EPA are considered highly relevant for assessing the potential risks associated with exposure to dental amalgam mercury. Introduction In the United States, people are exposed to mercury from three major sources: fish methylmercury , vaccines ethylmercury , and dental amalgams elemental mercury in the form of mercury vapor.

Previous Assessments by U. After a comprehensive review of the literature, the USPHS Report on Dental Amalgam provided the following conclusion regarding health risks relevant to FDA policies for dental amalgam: …current scientific evidence does not show that exposure to mercury from amalgam restorations poses a serious health risk in humans, except for an exceedingly small number of allergic reactions. The USPHS report provided the following conclusion, updating the USPHS conclusion: In , with input from a broad cross-section of scientists and dental professionals within USPHS, the FDA completed a review of nearly 60 studies that were published in peer reviewed scientific literature and were cited by citizen groups that petitioned the agency for stringent regulatory actions against dental amalgam.

A similar review by EPA of the literature up to pertinent to the cancer assessment for elemental mercury did not identify any critical new studies. A similar review of the literature up to pertinent to the cancer assessment for inorganic mercury did not identify any critical new studies.

A similar evaluation was performed by ATSDR in each year since the publication of the Toxicological profile, with new literature search coverage extending back to On the basis of standardized review criteria used for all ATSDR Toxicological Profiles and evaluation of studies potentially relevant to toxicity and the potential for human exposure, ATSDR concluded that as of July no studies were identified that would significantly change their toxicological evaluations for metallic or inorganic mercury.

Significant information is defined as information that is likely to change risk estimates by FDA for the use of dental amalgam Identify, using literature selection criteria Appendix A any peer-reviewed studies since contained in the literature reviews provided by ATSDR, EPA, and any governmental public health ministry, department, or agency that are noted by those reviews to be critical or important studies with respect to comprehension of health risk for inorganic or elemental mercury or to mercury in dental amalgam.

Provide critical review of each of the identified peer-reviewed studies with regard to quality and relevance to improve understanding of public health significance by evaluating, for example, study methods, study design, statistical power, and relevance to human health. Provide an overall assessment and summary conclusions regarding significant new information since regarding health risk from mercury in dental amalgam.

Specifically, what contributions have peer-reviewed studies published after made to our understanding of mercury-containing dental amalgams and their potential risk to human health? Update Review Strategy and Process Other government agencies and international organizations have evaluated the peer-reviewed scientific literature regarding human health effects and exposures to mercury that are relevant to assessing the health risks of mercury in dental amalgam. Summary of Previous Agency Reports The ASTDR MRLs for chronic elemental and inorganic mercury exposure derived in , and the EPA RfC for mercury vapor and RfD for mercuric chloride derived in , are health effects-based exposure reference values that have remained unchanged through and represent chronic and lifetime exposures considered to be highly protective for human health.

Review of Additional Scientific Literature In response to the charge for the current review, 29 human studies and 5 animal studies were reviewed and evaluated. Studies on human mercury toxicokinetics and exposure characteristics Seven articles addressing aspects of Hg exposure and distribution were identified. Studies on Human Occupational Exposures to Mercury Vapor and Outcomes Twelve articles on populations occupationally-exposed to mercury vapor were identified. Studies on General Mercury Exposure and Cardiovascular Disease A single article was identified that focused on the issue of cardiovascular health effects and exposure to Hg with dentists comprising a majority of the cohort studied.

Human Amalgam Exposures and Outcomes Seven reports dealing specifically with mercury dental amalgam exposures and outcomes were identified. Mercury Vapor and Neurobehavioral Outcomes Three studies were identified that examined the relationship between exposure to mercury vapor and behavioral outcomes. Maternal amalgam; maternal and infant blood and milk levels. Infant blood levels decrease after birth even while breast feeding. Strengths: humans, maternal, infant, and cord blood and milk levels.

Dye et al. Amalgam surfaces: Primarily serves as reference resource for exposure using association between dental surfaces and urinary Hg levels. Jonsson et al. No amalgam fillings Expired air; urine and plasma levels measured. Urine Hg — 0. Excretion in urine would not plateau for several months post-exposure for most subjects.

Strengths: Human subjects; 24hr urine levels; followed for 30 days. Weaknesses; small n; reported values in nmole. For this study: males, age yrs old avg. Urine - total and inorganic Hg levels were 3. Blood - total and inorganic Hg in whole blood were 2. Significant correlation found between amalgam exposure and total and inorganic Hg in urine, with or without corrections for creatinine. Weak but statistically significant correlation was found between whole blood and total and inorganic Hg. Results clearly show that Hg concentrations in blood and urine increase with amalgam exposure; however, no significant changes in Hg levels were found when data divided into different age groups.

Number and surface areas of dental amalgam fillings influence Hg concentration in amniotic fluid but not at a significant level; no adverse outcomes were detected through pregnancies and in the newborns. Evaluation of mercury in urine as an indicator of exposure levels of mercury vapor.

Compiles ten studies using different exposure scenarios to see if urinary Hg can be used as reliable predictor of Hg exposure. Includes two studies: Eti et al. For 3 , predicted urinary Hg levels are within background ranges. Total Environ. Dental amalgam. DMPS chelator injected — blood collected after 15, 30, and min, and 24 hrs; urine collected pre-chelator and at 30 min. Median amalgam surfaces: alleged Hg symptoms: This study evaluated the use of DMPS as a diagnostic tool in patients with symptoms allegedly caused by Hg from dental amalgam.

The DMPS exposure also reduced blood Hg levels within minutes in all alleged versus non-alleged groups. Occupational chloralkali workers previously exposed to Hg 0. Avg duration: Follow-up study: 41 exposed subjects and 40 controls had been previously evaluated 5 years earlier Ellingsen et al. Calculated cumulative U-Hg levels past exposure Hg-exposed workers: Current blood Hg total Hg workers: 4. No associations for any neuropsychologic or neurobehavioral tests.

Digit-symbol performance improved in past 5 years after exposure ceased. Exposure to amalgam Hg 0 used in dental occupation. No non-dental practitioner controls. Not reported. Retrospective cross-study of combined 5 psychomotor performance data from 6 previous studies conducted between and Some effect on Finger Tap Test but not significant.

Neurobehavioral effects from exposure to dental amalgam Hg 0: New distinctions between recent exposure and Hg body burden. Male and female subjects served as their own controls. Mean number of amalgams in mouth: 1. Strengths: Pre-chelation urine Hg levels are a metric of recent exposures; post-chelation levels represent longer term exposures body burdens.

Weaknesses: Duration of exposure unknown. No non-dental subjects with similar urine Hg levels.


  1. trace a person by telephone number!
  2. Agency considers further delay on Ohio River mercury rule.
  3. Mercury Contamination!
  4. a person looking out a door.
  5. mclean county north dakota dept of records!
  6. Possible chelation of other essential and non-essential metals. Chronic low-level mercury exposure, BDNF polymorphism, and associations with cognitive and motorfunction. Exposure to amalgams Hg 0 used in dental occupation. Adult male and females. Dentists: 3. BDNF polymorph mutants had affects not attributable to U-Hg on 4 measures in dentists and 3 measures in hygienists. Adult males and females. Same as the Neurotox. Study uses the same subjects as the Tox. Occupational chloralkali workers exposed to Hg 0 — avg duration — Dentists: Log ln 1. Letz et al.

    Mean age — 71 yrs. A battery of tests which includes both peripheral and central nervous system function were evaluated 30 years after heavy Hg exposure. Results showed that exposure to high levels of Hg can have adverse effects mostly on peripheral nerves long after the exposure occurred. Subclinical visual impairment assoc with Hg 0 exposure.

    Appears to be same subjects as used in the other Urban et al. Controls: not measured or reported. Photic driving is a physiologic response of EEG activity to intermittent photic stimulation. No significant associations between 5 parameters of photic driving and urinary Hg 24 hr and cumulative index [duration x U-Hg hr]. Visual Neurosci. Evaluated 5. Retinal function deficits as assessed via full-field electroretinograms and the Cambridge Color Test associated with Hg.

    Nothing else tested. Yoshizawa et al. N Engl J Med Mercury and the risk of coronary heart disease in men. Subjects from Health Professionals Follow-up Study. Significant correlation between toenail Hg levels and fish i. Nested case-control design. Findings do not support association between total Hg exposure and risk of coronary heart disease. Weak relationship cannot be ruled out. Health effects of dental amalgam exposure: A retrospective cohort study. Amalgam; New Zealand Defense. Retrospective epidemiology study. Amalgam surface years.

    Significant protective effect: HR 0. Strengths: detailed exposure data; large of health outcomes. Weaknesses; lack important covariates: smoking, drug and alcohol history; diet, disease, Pb exposure, no urinary Hg levels. JAMA Mean - 15 surfaces restored over 5 years range Total Hg - 0. Urinary albumin 7. No significant changes in IQ, memory, visuomotor function; urinary albumin renal effects ; if anything an increase in IQ favoring those kids with amalgam. Strengths: humans, prospective randomized clinical trial; children age at first exposure; relevant and well-standardized endpoints IQ evaluated 3 times; neuropsych assessments, 4 times.

    Weaknesses: only 5 years of exposure; earliest exposure to amalgam at 6 years. Mean - Follow-up was 7 years. Strengths: children age at start ; randomized clinical trial; relevant measures; repeated assessments; longitudinal; follow up was high. Weaknesses: only 7 years of follow up. Hg amalgam in adults at years of age. Exposure level correlations were done.

    Groups stratified: 0; ; ; ; total amalgams. Strengths: humans; long-term exposures; relevant endpoints; attempt to correlate exposure with effect dose-response: no association. Weaknesses: cross-sectional study; absence of data on date of amalgam placements, removed or replaced, but suspect exposures of years. Amalgam fillings note that this is not surfaces. Stratified into 0, or fillings for dose-response: correlation with low birth weight.

    Not reported Population-based, case-control study. No significant association with number of amalgam fillings placed during pregnancy and low birth weight. Neurotoxicology Significant effects on continuous vibrotactile response, but only in select groups i. Lack of dose-response. Strengths: Humans; amalgam. No females; Saxe et al. Number of amalgams; number of amalgam surfaces; amalgam location and duration U-Hg NA. Brain region Hg levels determined at autopsy. Regional Hg levels in brain did not correlate with the number of amalgams or surfaces.

    No differences between AD and control groups with respect to number of amalgams or surfaces. Dentists: 1. Similar article to Woods et al. Plausibility of hypothesis not evident, i. The association between genetic polymorphisms of coproporphyrinogen oxidase and an atypical porphyrinogenic response to mercuryexposure in humans. Dentists and Hygienists: 2. No neurotoxicity test information listed for the subjects in this manuscript. Davis et al. No significant effect on pregnancy rate, implantation sites, estrous cycles slightly prolonged in the 2 higher dose groups. Kidney levels were X brain levels with no histological evidence of toxicity in kidney.

    Strengths: some dose-response with effects; inhalation of elemental mercury; nose-only exposures; relevant endpoints. Weaknesses: rodent model; acute, urines collected immediately after exposures so real hr levels are not known; high doses maternal toxicity at high doses. Disposition of inhaled mercury vapor in pregnant rats: Maternal toxicity and effects on developmental outcome. NA Hg levels in tissues such as brain, liver, kidney increased in proportion to exposure concentration a and number of days in both maternal animals and offspring.

    When were assessments made? At what PND? Also, please list actual values. Urinary biomarkers elevated. Hg crossed the placenta and rate of elimination was higher in maternal tissue compare to fetal and especially when compared in the brain. Exposures are much higher than dental amalgam exposures. Herr et al. Prenatal in utero exposure study in rats. It was found that the number and surface areas of dental amalgam fillings influenced the Hg concentrations in amniotic fluid but not significantly.

    The report mentions that no adverse outcomes were detected throughout the pregnancies or in the newborns, but no outcomes were specified. Mercury in amniotic fluid has not been validated as a biomarker of exposure or effect. Strengths: human subjects; pregnant women; amniotic fluid levels.

    Weaknesses: difference in amniotic Hg levels between positive and negative groups was minimal. Tsuji et al. Evaluation of mercury in urine as an indicator of exposure to low levels of mercury vapor. This study reviews data from ten other studies using different exposure scenarios to see if urinary Hg can be used as a reliable predictor of airborne Hg exposure. Two studies using exposure via dental amalgam were included Eti et al. Strengths: summarizes previous work; human data; quantified exposures. Weaknesses: no effects data. Vamnes et al.

    Total Envir. Blood mercury following DMPS administration to subjects with and without dental amalgam. Hg exposure via dental amalgam was reported as amalgam surfaces. Persons with amalgams removed about 2. This study evaluated the use of chelation with DMPS 2, 3 dimercaptopropane-l-sulfonate to decrease blood levels of Hg, noting that urinary Hg levels without chelation are not complete measures of the effects of DMPS chelation of Hg.

    The blood levels of Hg were virtually identical in healthy subjects with amalgam versus subjects attributing symptoms to dental amalgam and in those individuals with amalgams removed. The data show that there is no difference in Hg blood levels in subjects with and without self-reported symptoms thought to be caused by amalgams and that chelation by DMPS is short-lived and has minimal impact on blood Hg levels. Strengths: human subjects; blood levels; chelation data.

    Weaknesses: no outcomes data. Summary of the studies on human mercury toxicokinetics and exposure characteristics. The data from these studies provide information on background levels of Hg in urine 0. In addition, there is good evidence that for every 10 Hg amalgam surfaces placed, urine Hg levels increase by 1 to 1. Airborne levels of 3 are not accurately reflected in urine Hg levels, whereas higher airborne levels produce urine Hg levels that do correlate with ambient exposures.

    Removal of a substantial number of Hg amalgam restorations does not result in a large decrease in blood Hg levels, even years after removal. And lastly, in utero fetal exposure to Hg-- presumably via exposure to maternal blood via placental transfer--is greater than postnatal exposure with neonatal Hg levels decreasing after birth even with continued exposure via breast milk.

    In addition, amniotic levels of Hg do not appear to be good biomarkers for the number of maternal amalgams, at least if there are 5 or fewer fillings. Bast-Pettersen et al. A neurobehavioral study of chloralkali workers after the cessation of exposure to mercury vapor. This was a clinical study designed to determine whether there were any lingering neurotoxicities from previous exposure to Hg vapor in 49 male chloralkali workers Extensive neurobehavioral assessments were carried out and many are the same or very similar to those utilized in the Echeverria et al.

    The mean ages of the 49 chloralkali workers and 49 controls were the same at Previous testing of 41 of the 49 workers with mean blood Hg levels of However, thedigit-symbol test did show a decreased performance that correlated with urine Hg levels at the time. When the workers were tested 5 years later there were again no deficiencies in any of the standard tests and the digit-symbol performance had improved. These data indicate that, at relatively low occupational exposures three to ten-fold greater than that expected from exposure to Hg from dental amalgams , minor deficits produced during exposure ameliorated after exposure ended.

    Strengths: human subjects; relatively low occupational exposures; longitudinal assessments of affected subjects; large number of outcome variables. Weaknesses: relatively small n. Bittner et al. Behavioral effects of low-level exposure to Hg 0 among dental professionals: A cross-study evaluation of psychomotor effects. Of the psychomotor measures examined, the IHST showed significant negative associations with log-transformed urinary Hg levels. Echeverria et al. Neurobehavioral effects from exposure to dental amalgam Hg 0 : new distinctions between recent exposure and Hg body burden.

    A key feature of this study was the use of the chelating agent DMPS 2, 3-dimercapto-propanesulfonate to assess Hg body burden. Pre-chelation urine Hg levels of 0. Pre-chelation urine levels were suggested to represent metrics of recent exposures whereas post-chelation levels were suggested to represent longer term exposures body burdens.

    Subtle but statistically significant associations were demonstrated for recent Hg exposure and measures of mood, motor function and cognition, whereas Hg body burden was associated with symptoms, mood, and motor function. Strengths: human subjects, relevant measures, pre- and post-chelation urine Hg levels. Chronic low-level mercury exposure, BDNF polymorphism, and associations with cognitive and motor function.

    This was a very comprehensive clinical study in dentists and dental assistants that reported the effects of a polymorphism in brain derived neurotrophic factor BDNF or Hg on motor activity and a variety of psychomotor functions digit span; hand steadiness; finger tapping; visual reproduction; pattern discrimination; digit-symbol; trailmaking; tracking.

    When present in the homozygous form in humans, the BDNF polymorphism affects a few of the same neurological functions that are affected in Hg intoxication. The study uses most of the same subjects as the Heyer et al. The Hg levels are slightly higher in this report than those reported by this group elsewhere Woods et al.

    Work is cited Aposhian indicating that dental groups excrete fold more Hg in urine after chelation with DMPS suggesting that the body burden of dental populations is much higher than that of non-dental populations. The authors found no significant effects of Hg or the BDNF allele on verbal intelligence or reaction times. Significant correlations between Hg levels in urine were found for 9 behavioral measures in dentists and 8 measures in assistants including visual discrimination, hand steadiness, finger tapping and trail making tests.

    The BDNF polymorphism was correlated with 4 behavioral measures in the dentists and 3 in the dental assistants. Urine Hg levels and the BDNF polymorphism were both correlated with effects on finger tapping in the dentists as well as hand steadiness and trail making B in the dental assistants. The authors report that several of the tests used e. It seems possible that the observed significance could be due to those subjects having the higher urinary Hg levels.

    Strengths: human subjects, relevant occupational exposures; extensive and relevant measures for several levels of the neuraxis. Weaknesses: lack of non-dental worker controls could maximize population homogeneity and the dental assistants were from the same clinics as dentists; both of these issues make it impossible to rule out workplace characteristics or exposures other than Hg that may have contributed to their findings; lack of association of effects with any index of cumulative or past peak Hg exposures.

    The association between a genetic polymorphism of coproporphyrinogen oxidase, dental mercury exposure and neurobehavioral response in humans. This was a follow-up clinical study in the same subjects dentists and dental assistants used in the Echeverria et al. In the present study the correlation of a CPOX4 polymorphism or urine Hg levels with a host of neurological endpoints was analyzed. The same correlations between urine Hg level and neurobehavioral measures as reported in Echeverria et al. As in the Echeverria et al. Significant correlations were found between urine Hg levels and 9 neurobehavioral measures in dentists digit span forward and backward; visual reproduction; symbol-digit; finger tapping dominant, non-dominant and alternate; hand steadiness; and tracking and 8 measures in assistants digit span forward; digit-symbol; pattern discrimination; trailmaking B; hand steadiness, finger tapping dominant, non-dominant and alternate; and vibration sensitivity.

    The CPOX4 polymorphism and urine Hg levels correlated with effects on two of the same measures in dentists and 3 in assistants. Strengths: human subjects, relevant exposures; extensive and relevant measures at several levels of the neuraxis. Weaknesses: lack of non-dental worker controls could maximize population homogeneity and the dental assistants were from the same clinics as dentists; both of these issues make it impossible to rule out workplace characteristics or exposures other than Hg that may have contributed to their findings. Occupational exposure to inorganic mercury vapour and reproductive outcomes.

    Forty-six women were exposed to inorganic Hg vapor at concentrations estimated to range from 0. Nineteen controls worked in the same factory but were not exposed to Hg vapor. Findings: possible association between Hg exposure and risk of adverse pregnancy outcome congenital abnormality but this observation was not statistically significant. Incidence was 4. Strengths: humans; relevant endpoints. Weaknesses: retrospective study from medical records; individual exposure data were incomplete; no urine Hg levels available; small n; significant differences in age between comparison groups; lack of dose-response relationship.

    Ellingsen et al. Neuropsychological effects of low mercury vapor exposure in chloralkali workers. This study examined 47 male chloralkali workers an average of 42 years old exposed to Hg vapor for an average of At the time of testing, mean urine Hg levels in the chloralkali workers were 5. After controlling for differences in intellectual level, there was a weak but significant association between exposure measures and tests of attention, psychomotor and visuomotor speed, and immediate visual memory span. Strengths: human subjects, relevant endpoints, urine and blood Hg levels, exposure histories.

    Weaknesses: referent group differed significantly on smoking and intellectual capacity. Heyer et al. Chronic low-level mercury exposure, BDNF polymorphism and associations with self-reported symptoms and mood. A clinical study looking at the correlation of urine Hg levels and a polymorphism V66M in the brain derived neurotrophic factor BDNF allele on self-reported symptoms and mood. When present in the homozygous form, V66M predisposes humans to many of the same neurological deficits seen with Hg intoxication. The authors hypothesized that this polymorphism might interact with Hg to produce exacerbated neurological deficits.

    The urine Hg levels reported here are slightly higher than those reported in Woods et al. The authors present their analysis of self-reported data obtained from questionnaires for evaluating a range of recent and chronic symptoms including mood, physical and other mental status. Three measures in dentists 2 in the predicted or worsening direction and 13 in dental assistants 11 in the predicted direction were correlated with urine Hg levels only. Strengths: human subjects; good n; large number of relevant observations; genetic markers.

    Residual neurologic deficits 30 years after occupational exposure to elemental mercury. This study reported findings from subjects exposed to very high Hg levels from an industrial setting dental amalgam exposures are unknown. Participants included former plant workers with exposed to inorganic Hg. An extensive battery of tests which assessed both peripheral and central nervous system function was used to evaluate participants almost 30 years after the documented heavy exposure when the average age was 71 years.

    The results showed that exposure to high doses of inorganic Hg can have long-lasting adverse effects, primarily on tests of peripheral nerve function. Postural tremor was assessed by physical examination and accelerometry and was weakly associated with past Hg exposure. Even with the aging participants having documented high Hg exposure, there was no correlation between prior Hg exposure and a variety of tests for dementia and declining cognitive functions. Only industrial exposure was considered in this study and Hg levels were much higher than those associated with dental amalgam.

    Strengths: human subjects; large n; large number of relevant endpoints. Weaknesses: only very high previous exposures to Hg. Urban et al. EEG photic driving in workers exposed to mercury vapors. This was a clinical study on the effects of previous exposure to Hg vapor in 24 male chloralkali workers average age It is not clear whether these are the same workers studied in their companion paper Urban et. A significant effect on photic driving of the EEG was found in both the plant workers and controls but a clear correlation between 24 hr Hg excretion was not found.

    Exposed workers had significantly increased photic driving responses compared to the control group, but the control group differed with respect to age they were years younger , alcohol and tobacco use they drank and smoked less. Strengths: human subjects; relevant endpoints. Color discrimination impairment in workers exposed to mercury vapor. This was a clinical study on the effects of previous exposure to Hg 0 vapor for almost 15 years Urine Hg levels of Color vision discrimination was impaired in the chloralkali workers, particularly with respect to the Blue-Yellow confusion axis test.

    Urine Hg levels and effects did not correlate or demonstrate a dose-response. Since this was a cross-sectional study, it is not known whether the observed effects at the time of testing could be the result of some previous higher exposures. The authors suggest that, based on their findings and others Cavalleri et al. Weaknesses: small n; no dose-response; weak relationship of exposure and effects.

    Ventura et al. Multifocal and full-field electroretinogram changes associated with color-vision loss in mercury vapor exposure. This was a clinical study in Sao Paulo to determine whether there were any lingering neurotoxicities from previous exposure to Hg 0 vapor in 43 male and female fluorescent lamp workers 9. The mean age of the 43 chloralkali workers was virtually identical to that of the 21 controls at slightly over 42 years. Color vision electroretinograms and performance of the Cambridge Colour Test were significantly worse in the lamp workers.

    Weaknesses: no measures of Hg exposure; no mention of amalgams; impossible to make inferences with respect to Hg exposure. Summary of studies on human occupational exposures to mercury vapor and neurobehavioral outcomes. Long-lasting effects from occupational exposures at relatively high levels. Only performance on the digital-symbol test showed significant effects of Hg exposure at the end of chronic exposure Thus, effects were not seen at urine Hg levels higher than those reported by Echeverria and coworkers and the effects waned with time.

    Most measures from the extensive test battery did not show any residual effects of exposure and there were no findings of effect on tests for dementia and other measures of declining cognitive function. Since Hg exposures were very high, it is difficult to determine how the findings relate to Hg exposure via dental amalgam. Other occupational studies have implicated prior exposure to Hg vapor as a causative factor in long-lasting adverse effects on color vision function; however, no biological measures of Hg exposure or amalgams were provided.

    Studies purporting to show increased photic driving responses in persons previously exposed occupationally to Hg vapor were confounded by the fact that the comparison group differed with respect to age and alcohol and tobacco use controls were younger and drank and smoked less. Thus, the data did not allow a determination as to whether previous Hg exposure accounted for the observed effects. Additionally, studies suggesting impaired color vision in persons previously exposed occupationally to Hg vapor were confounded by the lack of dose-response relationships urine Hg levels were obtained at the time of testing.

    In addition, the reported effects of Hg exposure were not strong. There was no association between occupational exposure to Hg and congenital malformations. Effects in dental professionals: Chelation of Hg in dental professionals suggests that the Hg body burden in this population of workers is much greater than indicated solely by pre-chelation urinary Hg levels. These studies did not include a cohort comprised of non-dental controls.

    This observation, coupled with a lack of association between the neurobehavioral outcomes and indices of long-term Hg exposures suggests that these effects may reflect confounding of Hg exposure with other occupational exposures, something that this type of study design cannot rule out. A single article was identified that focused on the issue of cardiovascular health effects and exposure to Hg with dentists comprising a majority of the cohort studied. Mercury and the risk of coronary heart disease in man. This was a nested, case-control clinical study Health Professionals Follow-up Study correlating, using the quintile approach, mercury inorganic plus organic sources, although not specified levels in toenail clippings with coronary heart disease in male health professionals out of the total 33, subjects had coronary heart disease or were heart attack victims during the 5 years of follow-up.

    A majority of the subjects were dentists and therefore were assumed to have had occupational mercury vapor exposures. Mercury in toenail clippings reflected both occupational exposure of the dentists and dietary fish intake. There was a significant correlation between toenail Hg levels and fish i.

    There were no significant differences between the toenail Hg levels in persons that suffered from coronary heart disease and those that did not. The number of amalgams in subjects was not determined. Based on the data from this report, there was no evidence that, at the exposure levels reported, mercury exposure from multiple sources contributed to coronary heart disease. Strengths; humans subjects; relevant endpoints; large n; longitudinal, case-control study. Weaknesses: toenail Hg has not been completely validated as a biomarker of Hg exposure; Hg exposures were from a variety of sources and included organic forms.

    Summary of studies on general mercury exposures and cardiovascular disease. This study was identified and reviewed since a majority of the subjects were dentists; thus, it is s ignificant in that it looked at both elemental and methylmercury exposures. No correlation was found between toenail Hg levels and fish i. There was no evidence of a link between Hg exposure elemental mercury and methylmercury and coronary heart disease in this study. However, some recent epidemiological studies in men focused on mercury exposure, primarily methylmercury from fish, suggest that methylmercury is associated with a higher risk of acute myocardial infarction, coronary heart disease, and cardiovascular disease in some populations.

    While important, the weight of evidence for cardiovascular effects is not as strong as it is for childhood neurological effects and the science is still being evaluated. EPA noted in that these findings to date and the plausible biological mechanisms warrant additional research in this area EPA, However, there is insufficient evidence to determine whether exposures to elemental mercury from dental amalgam are associated with cardiovascular disease.

    Further, cardiovascular disease has not been an endpoint evaluated in studies of elemental mercury exposure in chloralkali workers or and dental professionals. Seven reports dealing specifically with mercury dental amalgam exposures and outcomes were identified. Two were very recently published epidemiological studies in children. Bates et al.

    INTRODUCTION

    Health effects of dental amalgam exposure: a retrospective cohort study. Mercury exposures were quantified using amalgam surface years. No actual Hg tissue levels were reported. There was no association of amalgam exposure with Chronic Fatigue Syndrome, an endpoint of special interest in this population. There was demonstration of statistically significant protective effects of amalgam: HR 0. The weight of evidence does not suggest that exposure to amalgam causes significant adverse health effects. Strengths: large n; detailed exposure data; large number of health outcomes.

    Weaknesses: lack important covariates: smoking, drug and alcohol history; diet, disease, lead exposure, and perhaps, most importantly, urinary Hg levels. Bellinger et al. Neuropsychological and renal effects of dental amalgam in children: a randomized clinical trial. Subjects were followed for years after exposure with a mean of 15 surfaces range restored over 5 years. Only total urinary Hg values were reported 0.

    Hair levels were also reported. Urinary albumin levels were 7. Findings: none of the parameters evaluated reached statistical significance for adverse effects of amalgam exposure IQ, memory, visuomotor function ; furthermore, though not significant, the trends appeared to be in the direction of increased IQ rather than decreased with increasing amalgam exposure.

    Hg levels in urine increased a maximum of 1. This is less than the more than 1. Weaknesses: only 5 years of exposure; earliest exposure to amalgam at 6 years of age. DeRouen et al. Neurobehavioral effects of dental amalgam in children: a randomized clinical trial. A prospective study with a relatively large sample size of children living in Lisbon, Portugal, aged 8 to 10 years at the start of the study and who had no prior restorations.

    The m ean number of surfaces restored was Follow-up lasted for 7 years. Hg levels in the urine were only minimally increased 0. This is far less than the more than the 1. The peak mercury levels reached in the amalgam group were more than fold less than the lowest urine levels that have been reported as threshold for effects on vision and motor tremor, which are some of the neurological functions most sensitive to disruption by Hg Urban et al.

    Functional domains assessed included memory, attention, and visuomotor and nerve conduction velocities. Assessments were performed approximately on an annual basis. IQ was assessed at the beginning and the end of the study. Weaknesses: earliest age was years at start; only 7 years of follow up. Factor-Litvak et al. Mercury derived from dental amalgams and neuropsychologic function.

    Dose-response data were examined for the number of amalgams vs. Exposure level correlations were examined by stratifying groups into 0; ; ; ; and total amalgam surfaces. The data showed that urinary Hg levels increase with increasing amalgam surfaces for each 10 surfaces the urine Hg levels went up between 0. There was no evidence that dental amalgams produced neurotoxicity. Strengths: humans; long-term exposures; relevant endpoints; good n and power; attempt to correlate exposure level with effect dose-response: no association.

    Weaknesses: cross-sectional study; absence of data on when amalgams were actually placed, removed or replaced, but suspect exposures of years. Hujoel et al. Mercury exposure from dental filling placement during pregnancy and low birth weight risk. This study reported Hg exposure as number of amalgam fillings note that this was not number of surfaces.

    Data were stratified into 0, or fillings for dose-response analyses concerning low birth weight. There was no significant association with dose of inorganic Hg number of amalgam fillings and low birth weight. Strengths: human subjects, large n; case-control study. Weaknesses: no urine Hg levels. Kingman et al. Amalgam exposure and neurological function.

    Urine Hg levels were not given in this study but can be inferred through the earlier Kingman et al. Significant but marginal effects were observed on continuous vibrotactile response, but only in select groups i. There was no dose-response in the findings. Strengths: humans subjects; amalgam exposures; large n. Weaknesses: lack of continuous variables i. Regional brain levels of Hg were determined at autopsy in 68 subjects with AD and in 33 controls.

    Regional Hg levels in the brain did not correlate with the number of amalgams and there were no differences between the AD and the control group with respect to number of amalgams. The authors concluded that the Hg levels were not elevated in persons with AD and that the number of amalgams could not be shown likely to affect the incidence of AD. Weaknesses: even with relatively high numbers for a tissue analysis study, the number of subjects was low.

    Summary of human amalgam exposures and outcomes. Collectively, these studies provide some of the most important and relevant new observations concerning the possibility that mercury amalgam might result in adverse human health effects in persons with amalgam restorations. The two clinical trials in children also provide data for a very important sensitive subpopulation. The large retrospective studies have large sample sizes.

    Considering all of the studies, the data do not support adverse effects of mercury amalgam in the groups evaluated. In those studies where a significant association was noted i. For the MS observation, it was noted that the incidence of MS in the study population was well below that of the general population. In addition, there were significant Hg-related decreases in hazard ratios for several outcomes including kidney disorders, inflammatory responses and toxic neuropathy in the same study.

    An additional cross-sectional study in adults found no correlation between urine Hg levels and a variety of endpoints assessing several levels of the neuraxis. In the study showing significant correlations between number of amalgam surfaces and decreased vibrotactile response, it was noteworthy that the effect was demonstrable only in select groups. In addition, there were no urine Hg data presented in that particular study, making both interpretation and dose-response analysis difficult; e. The two clinical trials in children found no correlations between amalgam placements and adverse effects even with extensive and repeated assessments of a multitude of neurobehavioral functions.

    Thus, the weight of evidence from these studies that provide the most relevant data clearly do not support the hypothesis that exposure to mercury via dental amalgam restorations causes adverse biological outcomes. Five studies examined the ability of human genetic polymorphisms to alter biological responses to mercury exposure.

    This was a very comprehensive clinical study also discussed earlier under occupational exposures in dentists and dental assistants that reported the effects of a brain derived neurotrophic factor BDNF polymorphism Val66MET or Hg on motor activity and a variety of psychomotor functions e. There were no significant effects of Hg or the BDNF polymorphism on verbal intelligence or reaction time. In this study, as in the previous work from this group, several quantitative measures of neural function were analyzed.

    The BDNF polymorphism was correlated with effects on 4 measures in the dentists and 3 measures in the assistants. Both the BDNF polymorphism and urine Hg levels correlated with scores on finger tapping in the dentists and hand steadiness and trail making in the dental assistants. The authors suggest the possibility of additive effects between Hg exposure and the BDNF polymorphism for these measures, implying that persons with the BDNF polymorphism may be at greater risk of Hg effects. This is a follow-up clinical study in the same subjects dentists and dental assistants used in the Echeverria et al.

    In the present study, correlation of a CPOX4 polymorphism alteration in exon 4 of the gene encoding the coproporphyrinogen oxidase enzyme of the heme synthetic pathway or urine Hg levels with a host of neurological endpoints were analyzed. Significant correlations were found between urine Hg levels and 9 neurobehavioral measures in dentists digit span forward and backward; visual reproduction; symbol-digit; finger tapping dominant, non-dominant and alternate; hand steadiness; and tracking and 8 measures in assistants digit span forward; digit-symbol; pattern discrimination; trailmaking B; hand steadiness; finger tapping dominant, non-dominant and alternate; and vibration sensitivity.

    In addition, the CPOX4 polymorphism alone was associated with 4 measures in dentists spatial span, pattern memory, symbol digit, vigilance and 5 in dental assistants digit span, visual reproduction, symbol digit, simple and choice Reaction Times. The authors suggest the possibility of additive effects between the CPOX4 polymorphism and Hg exposure which suggests that persons with the CPOX4 polymorphism may be at greater risk for Hg effects. The authors present their analysis of self-reported data obtained from questionnaires for evaluating a range of recent and chronic symptoms including mood, and physical and other mental status.

    They observed 3 significant correlations between the BDNF polymorphism alone a p value of 0. Three measures in dentists 2 in the predicted direction and 13 in dental assistants 11 in the predicted direction were correlated with urine Hg levels only. Although it was suggested that persons with the BDNF polymorphism may be at greater risk from Hg exposure, there was only one outcome that correlated with both urinary Hg and the BDNF polymorphism in this study.

    Strengths: human subjects; large n; large number of relevant observations; genetic markers. Weaknesses: lack of non-dental worker controls; dental assistants were from the same clinics as dentists. A cascade analysis of the interaction of mercury and coproporphyrinogen oxidase CPOX polymorphism on the heme biosynthetic pathway and porphyrin production. There were no non-dental worker controls and the number of years of exposure to amalgam were not reported here. The subjects are very likely a subset of those in other studies Echeverria et al. This work basically revisits earlier work Woods et al.

    However, there is no explanation of why this would be relevant to any blood disorders or other adverse effects. This manuscript is clinically oriented but is more of a review article about remodeling and refining the ways in which Hg can interact with humans having the CPOX4 allele to affect products and intermediates in the heme biosynthetic pathway. Strengths: human subjects, relevant endpoints; genetic markers. Weaknesses: lack of non-dental worker controls could maximize population homogeneity; dental assistants were from the same clinics as dentists; both of these issues make it impossible to rule out workplace characteristics or exposures other than Hg that may have contributed to their findings; there is no discussion of an association of altered heme synthetic pathways and adverse biological effects.

    Woods et al. The association between genetic polymorphisms of coproporphyrinogen oxidase and an atypical porphyrinogenic response to mercury exposure in humans. The number of amalgams is not reported in this study. Since there are no non-dental controls there could be another factor s that the dentists and dental assistants have in common other than Hg exposures to influence the findings.

    Weaknesses: lack of non-dental worker controls; dental assistants were from the same clinics as dentists; no discussion of how altered heme synthetic pathways as reported here might lead to potential adverse effects. Summaries of studies that examined the relationship between human genetic polymorphisms and urine Hg levels to alter biological responses. All of the studies in this section were carried out in the same human subjects or subsets of the same populations. Thus, to varying degrees, they all share different strengths but the same weaknesses.

    These studies lacked the use of non-dental worker controls, thus the issue of selection bias arises. In addition, the dental assistants chosen as participants were from the same clinics as the participating dentists. There were often no associations between the outcomes of interest and any index of cumulative or past peak Hg exposures. These issues make it impossible to rule out workplace characteristics or exposures other than Hg that may have contributed to the findings from all of these papers.

    Thus, interpretation of the data for those with dental amalgam restorations is more difficult. Given these deficiencies, it does appear that BDNF and CPOX polymorphisms are associated with alterations in important behavioral responses nervous system functions. Mercury vapor and female reproductive toxicity. Adult female rats were exposed nose only to Hg vapor over postnatal days PNDs There were no significant effects of Hg vapor exposure on pregnancy rate or number of implantation sites.

    Estrous cycles were slightly prolonged in the 2 higher dose groups, and progesterone and estradiol levels were significantly different in the high dose group. Kidney Hg levels 0. Strengths: some dose-response information; inhalation of elemental mercury which is relevant to amalgam; nose-only exposures eliminates deposition on fur and subsequent ingestion; relevant endpoints.

    Weaknesses: rodent model; short-term exposures, urine samples were collected immediately after exposures so hr levels are not known; high doses maternal toxicity occurred at high doses. Morgan et al. Deposition of inhaled mercury vapor in pregnant rats: maternal toxicity and effects on developmental outcome. Hg levels were measured in brain, liver and kidney in both exposed maternal animals and offspring and several other maternal tissues. Hg levels increased in a dose-dependent manner in all tissues.

    No exposure-related histopathology was seen in lung, kidney or livers of pregnant animals when examined at several time points: gestational days 6 or 15 or postnatal day 1. Adverse effects on developmental outcome increased resorptions; decreased litter size and pup body weights occurred only at exposure levels that also caused maternal toxicity, i.

    Weaknesses: rodent model; short-term exposures, urine samples collected immediately after exposures so hr levels are not known; high doses maternal toxicity occurred at high doses. Summary of animal studies that looked at issues of maternal and reproductive toxicity. Both studies indicate that there is no development toxicity associated with mercury vapor exposures that do not also cause maternal toxicity.

    Three studies were identified that examined the relationship between exposure to mercury vapor and behavioral outcomes. Evaluation of sensory evoked potentials in Long Evans rats gestationally exposed to mercury Hg 0 vapor. Offspring one male and female per litter were evaluated as adults between at postnatal days and Brain Hg levels were not reported for the animals in this study but these animals were given an exposure identical same lab to that reported to produce Hg levels of 0.

    Those data showed that very little Hg crosses the placenta into the pups after maternal exposures. The neurological evaluations flash evoked potentials; pattern evoked potentials; compound nerve action potentials; cortical somatosensory evoked potentials; brainstem auditory evoked response; cerebellar somatosensory evoked potentials; nerve conduction velocity showed no conclusive effects on any measure tested; compound nerve potentials suggested a slight, but not significant, trend toward impairment.

    The study concluded that there were no effects of prenatal Hg exposure on responses evoked from peripheral nerves or the somatosensory, auditory or visual modalities. Strengths: sampled a variety of levels of the neuraxis; mercury vapor was used; gestational exposure; assessed long-term residual effects in adulthood PND Weaknesses: rats; high dose exposure. Yoshida et al. Susceptibility of metallothionein-null mice to the behavioral alterations caused by exposure to mercury vapor at human-relevant concentration.

    This study utilized adult female mice with mutant metallothionein genes that are nonfunctional knocked out - KO versus animals with wild type metallothionein genes to look at how the metallothionein function affects the neurotoxicity produced by exposure to Hg vapor whole body immersion at 0.

    Highlights

    At necropsy, the brain Hg levels in the metallothionein KO mice were 0. KO mice had a higher open field activity and poorer performance in passive avoidance test than the wild type mice. Hg toxicity and lower brain Hg levels were observed in KO mice compared to wild type mice. Behavioral changes in metallothionein-null mice after the cessation of long-term, low-level exposure to mercury vapor.

    This study was an adult mouse study very similar to Yoshida et al.

    Mercury Safety

    Evaluations for neurotoxicity occurred at the end of exposure and 12 weeks later and included locomotor activity open field behavior , learning ability passive avoidance , and spatial learning ability Morris water maze. After 29 weeks of exposure, metallothionein knock-out KO mice had brain Hg levels of 0. At the end of exposure, locomotor activity was marginally depressed in both strains, while 12 weeks later it was marginally increased in both strains. Performance of the Morris water maze was not affected at any time point.

    The authors note their findings were the first to indicate that long-term, low-level Hg vapor can lead to persistent neurobehavioral effects. The effects reported did not follow the prediction that higher brain Hg levels are associated with greater neurological impairments. Summaries of studies that examined the relationship between exposure to mercury vapor and behavioral outcomes. The findings that lower brain Hg levels were associated with a greater degree of neurological deficit and the lack of concurrent controls in this study make the data difficult to interpret.

    The data from these studies do not provide information useful for addressing issues related to the effects of Hg vapor at the levels experienced by persons with amalgam restorations. Consistent with previous reviews USPHS, ; ; ATSDR, of the literature, a positive association was observed between urinary mercury values and the number of amalgam fillings or surfaces placed Kingman et al, ; Factor-Litvak et al.

    It is clear that persons chronically exposed to mercury vapor in the workplace can suffer adverse health effects that often manifest as decrements in nervous system function. In some cases, recovery of function occurs after exposure has ended even though the process may take several years. General cognitive function and intellectual capacity appears to be relatively unaffected in such cases. Occupational exposure of dentists and dental assistants to mercury vapor appears to increase Hg body burden that is not reflected in urine mercury levels. The data are not sufficient at present to conclude whether this increase in mercury body burden results in adverse neurobehavioral outcomes.

    Clinical trials in children have provided critical observations concerning the effects of exposure to mercury from dental amalgam. Extensive, repeated assessments of a multitude of neurobehavioral functions demonstrated that there were no correlations between amalgam placements and adverse effects. Data from retrospective studies in large populations of adults do not support the finding of adverse effects of mercury amalgam and in a cross-sectional study there was no correlation between urine mercury levels and a variety of endpoints assessing several levels of the neuraxis.

    Fetal levels of mercury are generally much less than maternal levels and decrease after birth even when exposure via breast milk continues. The weight of evidence from human clinical and epidemiological studies of mercury amalgam does not support the hypothesis that exposure to mercury via dental amalgam restorations causes adverse biological outcomes. Data from animal studies indicate that there is no developmental toxicity associated with mercury vapor exposures that do not also cause maternal toxicity.

    Gestational exposures to relatively high concentrations of mercury vapor did not result in any significant adverse effects on a variety of sophisticated electrophysiological outcomes in rat offspring when tested as adults. Based on an evaluation of the extensive literature reviews conducted by ATSDR , and EPA , and an assessment of the health effects-based exposure reference values for elemental mercury derived by those agencies and WHO and ACGIH, no information was found that would change the comprehension of health risks for inorganic or elemental mercury and mercury in dental amalgam.

    Compared to previous analyses performed by USPHS, no significant new information was discovered from the review of these 34 articles that would change the risk estimates by FDA for the use of dental amalgam. It is concluded that there is insufficient evidence to support an association between exposure to mercury from dental amalgams and adverse health effects in humans, including sensitive subpopulations. Neurotoxicology ; 26 3 Int J Epidemiol ; 33 4 J Am Med Assoc ; 15 Neurotox Teratol ; 20 4 Environ Hlth Perspec ; 10 : Toxicol Sci ; J Am Med Assoc ; 15 : Occup Environ Med ; 62 6 Neurotoxicol Teratol ; 27 6 Neurotoxicol Teratol ; 28 1 Occup Med ; 47 6 Neurotoxicol ; Environ Health Perspect ; 5 Toxicol Sci ; 82 1 Toxicol Sci ; 81 2 Tox Lett ; Am J Epidemiol ; 8 Toxicol Appl Pharmacol ; Neurotoxicology ; 26 2 J Dent Res ; 77 3 Neurotoxicol ; 21 4 Arch Gynecol Obstet ; 2 J Am Dent Assoc ; Environ Health Perspect ; 4 Neurotoxicology ; 24 1