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Mercury, Lead, and Zinc in Baby Teeth of Children with Autism Versus Controls
Abstract
This study determined the level of mercury, lead, and zinc in baby teeth of children with autism spectrum disorder (n = 15, age 6.1 +/- 2.2 yr) and typically developing children (n = 11, age = 7 +/- 1.7 yr). Children with autism had significantly (2.1-fold) higher levels of mercury but similar levels of lead and similar levels of zinc. Children with autism also had significantly higher usage of oral antibiotics during their first 12 mo of life, and possibly higher usage of oral antibiotics during their first 36 mo of life. Baby teeth are a good measure of cumulative exposure to toxic metals during fetal development and early infancy, so this study suggests that children with autism had a higher body burden of mercury during fetal/infant development. Antibiotic use is known to almost completely inhibit excretion of mercury in rats due to alteration of gut flora. Thus, higher use of oral antibiotics in the children with autism may have reduced their ability to excrete mercury, and hence may partially explain the higher level in baby teeth. Higher usage of oral antibiotics in infancy may also partially explain the high incidence of chronic gastrointestinal problems in individuals with autism.
... In contrast, plasma offers only short-term information on Hg exposure, making it less crucial as a clinical matrix in ASD [119]. Therefore, it is imperative to conduct comprehensive studies on the Hg status in the blood, hair, and urine of pregnant women, lactating women, and young children to gain in-depth insights into prenatal and early postnatal Hg exposure, potentially during the period when ASD begins to develop [41]. For instance, a study by Ryu et al. [120] found a connection between prenatal and early childhood Hg exposure and ASD behavior at age 5 by analyzing Hg levels from early pregnancy to age 3 in a longitudinal cohort study of 458 mother-child pairs. ...
... Compared to other biological materials, deciduous teeth are perhaps the most promising clinical matrices for examining the link between Hg and ASD. Unfortunately, only two studies have been published on this topic to date, making it impossible to conduct a meta-analysis [41,112]. For a comprehensive understanding of the role of Hg in ASD, it is important to analyze tooth enamel rather than the entire tooth or dentin, because deciduous teeth's enamel begins to develop in utero, and concludes between 3 months and 1 year after birth. ...
... This provides insight into prenatal and early postnatal exposure, a critical period when ASD begins to develop [112]. Of note, the Hg levels recorded by Adams et al. [41] for neurotypical children corresponded to levels found in brain tissue from monkeys subjected to thimerosal, simulating the US childhood vaccination schedule, emphasizing the importance of deciduous teeth, particularly enamel, in understanding the role of Hg in ASD. Hg levels ranging from 260 to over 600 ng/g have been reported in Minamata disease [41]. ...
Mercury (Hg) is a non-essential trace metal with unique neurochemical properties and harmful effects on the central nervous system. In this study, we present a comprehensive review and meta-analysis of peer-reviewed research encompassing five crucial clinical matrices: hair, whole blood, plasma, red blood cells (RBCs), and urine. We assess the disparities in Hg levels between gender- and age-matched neurotypical children (controls) and children diagnosed with autism spectrum disorder (ASD) (cases). After applying rigorous selection criteria, we incorporated a total of 60 case-control studies into our meta-analysis. These studies comprised 25 investigations of Hg levels in hair (controls/cases: 1134/1361), 15 in whole blood (controls/cases: 1019/1345), 6 in plasma (controls/cases: 224/263), 5 in RBCs (controls/cases: 215/293), and 9 in urine (controls/cases: 399/623). This meta-analysis did not include the data of ASD children who received chelation therapy. Our meta-analysis revealed no statistically significant differences in Hg levels in hair and urine between ASD cases and controls. In whole blood, plasma, and RBCs, Hg levels were significantly higher in ASD cases compared to their neurotypical counterparts. This indicates that ASD children could exhibit reduced detoxification capacity for Hg and impaired mechanisms for Hg excretion from their bodies. This underscores the detrimental role of Hg in ASD and underscores the critical importance of monitoring Hg levels in ASD children, particularly in early childhood. These findings emphasize the pressing need for global initiatives aimed at minimizing Hg exposure, thus highlighting the critical intersection of human–environment interaction and neurodevelopment health.
... The detailed map of the spatial distribution of ions in human primary teeth highlighted distinct patterns with key differences in enamel and dentine: very high Mn levels at the pulp-dentine junction and demarcated high Mn zone in prenatally formed dentine. This method may provide a chronological record of variation in elemental intensities in different regions of dental tissues that calcify at different times in life [42]. ...
... In a case of natal tooth a mother diseases, dietary habits, environment and lifestyle habits (cigarettes, drugs) are the most important factors influencing the trace elements concentration in dental tissues. At the time of intensive growth and development children are vulnerable to the toxic effects of heavy metal exposure [42]. The most prominent period is the prenatal life. ...
... Prenatal and early environmental exposures have been implicated in developmental disturbances in children [41,42]. The current study provides an examination of natal tooth and showed deposition of potentially toxic trace elements in dental tissues. ...
Purpose
Tooth enamel might provide past chronological metabolic, nutritional status and trace metal exposure during development. Thus, the trace elements distribution embedded in tooth tissues represents an archive of the environmental conditions. The choice of biomarker is estimated as critical to the measurement of metal exposure. Natal teeth are defined as teeth being present at birth.
Methods
LA-ICP-MS provides a quantitative assessment of spatial distribution of trace elements in a natal tooth. The objective of the current study was to compare concentrations of building and other elements in a rare but reliable and valid biomarker - natal tooth.
Results
It have been reported presence of potentially toxic elements: Pb, Cu, Mn, Cd, Ni distributed in prenatally and perinatally formed enamel and dentine.
Conclusions
Analyses of deciduous enamel can provide answers into individuals’ earliest development, including critical pre- and perinatal period.
... 30 In a study conducted by Adams et al., the levels of Hg, Pb and Zn in the baby teeth of children with autism were compared to those of a control group. 31 The results showed that children with autism exhibited significantly elevated levels of Hg, while the levels of Pb and Zn were comparable to those observed in the control group. This study indicates that children with autism may have had a greater accumulation of Hg in their bodies during fetal and infant development. ...
... The researchers also suggest that the increased use of oral antibiotics in children with autism could have hindered their ability to eliminate Hg, thereby contributing to the higher levels of the element observed in their baby teeth. 31 The study conducted by Figueroa-Romero et al. aimed to investigate the potential dysregulation of metal uptake during childhood in individuals who were later diagnosed with amyotrophic lateral sclerosis. 32 By examining the co-exposure to different elements, the researchers found a strong association between childhood metal dysregulation and the development of amyotrophic lateral sclerosis. ...
... [6] Additionally, a study found that children with autism had double the Hg levels in their baby teeth compared to typical children. [7,8] ...
... Examples include the commonly known Hg, manganese (Mn), iron (Fe), cobalt, nickel, copper, zinc (Zn), cadmium (Cd), arsenic (As), chromium, lead (Pb), silver, and selenium as heavy metals. [7][8][9][10] ...
Autism spectrum disorder (ASD) encompasses a diverse range of conditions characterized by difficulties in social skills, repetitive behaviors, speech, and nonverbal communication. It is important to note that ASD does not have a single identifiable cause; rather, it arises from the complex interplay between genetic susceptibility and exposure to environmental factors. Impacting approximately 1% of all children, autism spectrum disorder is linked to toxic heavy metals and other potential environmental hazards that may contribute to its development, in conjunction with intricate genetic elements. This review aims to establish a connection between heavy metals and autism, presenting findings from experimental studies that investigate the relationship between heavy metal exposure and autism.
... However, a comprehensive metallomics investigation utilizing hair samples from children with ASD indicated that the youngest group (infants aged 0-3 years) had the highest lead burden, suggesting a link between early perinatal exposure and ASD [23]. However, some studies failed to identify a connection between lead levels and the prevalence of ASD [25,26]. A recent meta-analysis that included the findings of 48 independent research studies discovered substantially higher lead hair concentrations in ASD patients compared to controls [38]. ...
... ASD has been linked to higher mercury levels, according to many studies [16,19,22,27], with an emphasis again on the pre-and early postnatal developmental period. For example, the primary teeth of children with ASD show considerably greater mercury amounts [26]. However, no significant differences were discovered when measuring enamel that is created later in life [48]. ...
Since hundreds of years ago, metals have been recognized as impacting our body’s physiology. As a result, they have been studied as a potential cure for many ailments as well as a cause of acute or chronic poisoning. However, the link between aberrant metal levels and neuropsychiatric illnesses such as schizophrenia and neurodevelopmental disorders, such as autism spectrum disorders (ASDs), is a relatively new finding, despite some evident ASD-related consequences of shortage or excess of specific metals. In this review, we will summarize past and current results explaining the pathomechanisms of toxic metals at the cellular and molecular levels that are still not fully understood. While toxic metals may interfere with dozens of physiological processes concurrently, we will focus on ASD-relevant activity such as inflammation/immune activation, mitochondrial malfunction, increased oxidative stress, impairment of axonal myelination, and synapse formation and function. In particular, we will highlight the competition with essential metals that may explain why both the presence of certain toxic metals and the absence of certain essential metals have emerged as risk factors for ASD. Although often investigated separately, through the agonistic and antagonistic effects of metals, a common metal imbalance may result in relation to ASD.
... By our review of the literature, several dozen studies have explored the properties of teeth as indicators of mental health risk, in a mixture of clinical, community-based, and populationbased samples of youth (see Table 1). The overwhelming majority of research on teeth and mental health has investigated the associations of early life toxicants measured in primary teeth and risk for autism (30)(31)(32)(33)(34)(35)(36)46) in particular, as well as internalizing and externalizing problems (40,41), ADHD (37), schizophrenia (42,43), and neurodegenerative disorders (38,39) [see reviews by (47,48)]. The most recent generation of these toxicant teeth studies, which date back to the early 2010s, use mass-spectrometry technology paired with laser ablation. ...
... Early-life toxicant exposure (laser ablation) Autism Studies typically report differences in prenatal and early postnatal levels of heavy metals, as well as in the cyclic variation of metal concentrations, between children diagnosed with autism and controls. (30)(31)(32)(33)(34)(35)(36) ADHD Regularity and complexity of elemental cycles (for cobalt, lead, and vanadium) was reduced in children diagnosed with ADHD compared to those diagnosed with autism, along with other element specific features. ...
Mental disorders are among the most disabling health conditions globally. However, there remains a lack of valid, reliable, noninvasive, and inexpensive biomarkers to identify (at an early age) people who are at the greatest risk of experiencing a future mental health condition. Exfoliated primary teeth, when used in combination with established and emerging tools (e.g., family history, imaging, genetics, epigenetics), may provide important additional insights about vulnerability to mental illness. Teeth are especially promising because they develop in parallel with the brain and maintain a permanent record of environmental insults occurring during prenatal and perinatal development. Despite their potential, few empirical studies have investigated features of exfoliated teeth in relation to mental health. Here, we used micro-CT imaging to test the hypothesis that measures derived from exfoliated primary incisors associated with psychopathology symptoms in a community-based sample of children ( n = 37). We found that enamel volume (β = −0.77, 95% CI, −1.35 to −0.18, P = 0.01) had large negative associations with internalizing symptoms, and enamel mineral density (β = 0.77, 95% CI, 0.18–1.35, P = 0.01) had large positive associations with internalizing behavioral symptoms, even after stringent control for multiple testing. Pulp volume (β = −0.50, 95% CI, −0.90 to −0.09, P = 0.02) had a moderately-large negative association with externalizing behavioral symptoms, though these associations did not survive multiple testing correction. These results support the ongoing investigation of teeth as potential novel biomarkers of mental health risk.
... Among several studies carried out between 1999 and 2016, 74% of them revealed an essential link between ASD progression and mercury levels (Kern et al. 2016). Some studies revealed reports of increased mercury levels in teeth of ASD patients and demonstrated that enhanced mercury levels in the body might be due to reduced rate mercury excretion by excessive administration of oral antibiotics (Adams and Romdalvik 2007). An Egyptian study revealed greater mercury levels in the hair and blood samples of ASD patients (Yassa 2014). ...
... Various studies revealed the presence of mercury in teeth of ASD patients (Adams and Romdalvik 2007) ...
Autism spectrum disorder (ASD) is a developmental disorder of the brain characterized by shortfall in the social portfolio of an individual and abbreviated interactive and communication aspects rendering stereotypical behavior and pitfalls in a child’s memory, thinking, and learning capabilities. The incidence of ASD has accelerated since the past decade, portraying environment as one of the primary assets, comprising of metallic components aiming to curb the neurodevelopmental pathways in an individual. Many regulations like Clean Air Act and critical steps taken by countries all over the globe, like Sweden and the USA, have rendered the necessity to study the effects of environmental metallic components on ASD progression. The review focuses on the primary metallic components present in the environment (aluminum, lead, mercury, and arsenic), responsible for accelerating ASD symptoms by a set of general mechanisms like oxidative stress reduction, glycolysis suppression, microglial activation, and metalloprotein disruption, resulting in apoptotic signaling, neurotoxic effects, and neuroinflammatory responses. The effect of these metals can be retarded by certain protective strategies like chelation, dietary correction, certain agents (curcumin, mangiferin, selenium), and detoxification enhancement, which can necessarily halt the neurodegenerative effects.
Graphical abstract
... Interestingly, the levels of heavy metal in blood, urine, teeth, hair, and related body fluid or tissues in ASD children are inconsistent. Some studies demonstrated that the levels of Pb, Hg, As, Cu, and Cd were significantly higher in the autism children than healthy controls [3], while the significantly reduced levels of Mg and Se were well associated with the severity of ASD [4]. Some studies even used chelating agents to reduce the blood levels of Pb and Hg and found that the symptoms of autism alleviated with the reduced blood Pb and Hg levels [5,6]. ...
... ± 5.04, p < 0.001 in urine was significantly increased [13]. Also, the levels of Hg, Pb, and Zn were measured in the teeth of ASD and healthy children, which showed that the teeth Hg level was significantly higher in the ASD children (2.1-fold) than the controls, while the Pb and Zn levels were similar between the two groups [3]. Furthermore, the Pb (31.9 µg/L in ASD children, and were significantly lower in ASD children than the controls [14]. ...
Background
The etiologies of autism spectrum disorder (ASD) are yet unclear. Previous studies suggested that ASD is associated with environmental heavy metals. Thus, the present study analyzed the levels of 41 heavy metals and the associated environmental factors in children with ASD.
Methods
The 25 children diagnosed with ASD were included in the case group (ASD group), while the 18 age- and gender-matched healthy children who came for routine care were included in the typical development group (TD group). The levels of heavy metal in the blood were measured in both groups. The questionnaire survey collected the demographic information, socioeconomic information, and risk factors of potential heavy metal sources for the analysis of risk factors.
Results
A total of 25 children were included in the ASD group and 18 in the TD group. The blood manganese (Mn) level was significantly higher in the ASD group than the TD group . The father’s educational level was significantly higher in the ASD group than the TD group. The living status was mainly scattered for the ASD children and daycare for the TD group. The frequency of book-reading, washing hand with sanitizer/soap, and the folic acid intake by the mother before pregnancy was significantly lower in the ASD group than the TD group, while the percentage of birth disorder history was significantly higher in the ASD group than the TD group. Binary logistic regression analysis showed that the folic acid intake by the mother before pregnancy and father’s education level beyond junior college were protective factors for ASD. Also, the frequencies of washing hands with sanitizer every time, sometimes, and hardly acted as protective factors for ASD.
Conclusion
Blood Mn level was significantly higher in ASD than TD, suggesting that environmental Mn exposure could be a risk factor of ASD in children. Folic acid intake by the mother before pregnancy and father’s education levels are protective factors for ASD. Concentrated heavy metal in the blood in prenatal or early life exposures which suggested ASD is needed in the future study.
... The Autism Spectrum Disorder (ASD) is a complex developmental disorder that impairs human communication and social behavior (Currenti, 2010). Recently, numerous studies have reported the influence of environmental and genetic factors on the neurodevelopment, leading to the appearance of ASD in different populations (Adams et al., 2007;Fido and Al-Saad, 2005;Mohamed et al., 2015;Yassa, 2014;Yasuda et al., 2013). Although the exact causes of ASD are unknown, it is generally believed that multiple genetic and environmental factors may be involved (Tamás et al., 2014). ...
... A study involving South Indian autistic children revealed a strong correlation between autism severity and the extent of trace element exposures (Lakshmi Priya and Geetha, 2011). Similar results were reported in several other studies conducted in different worldwide populations (Adams et al., 2007;Yassa, 2014;Yasuda et al., 2013). ...
... Children with ASD had significantly 2 fold higher levels of Hg than control. However, no significant differences appeared in levels of Pb and Zn between the two groups (Adams et al., 2007). ...
... In the meantime, the clinical presentation of ASD is clearly varying and can present as a collection of health issues and comorbidities [8,9], not limited to neurodevelopmental, language, or social challenges [10][11][12][13][14][15]. Comorbidities include immune dysregulation [16][17][18][19][20][21][22][23], gastrointestinal issues such as diarrhea, constipation, and dysbiosis, mitochondrial dysfunction [24][25][26][27], poor detoxification [28], inflammation [29], food sensitivities, evidence of environmental toxicants [30][31][32][33][34][35][36][37][38][39][40][41][42], retained reflexes [43,44], and other structural or functional challenges. ...
The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990’s, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating the reversal of autism diagnoses, with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism symptoms among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD “requiring very substantial support” at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin’s symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins’ symptoms, which manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing modifiable environmental and lifestyle risk factors.
... ASD can present as a collection of health issues and comorbidities [8,9] not limited to neurodevelopmental, language, or social challenges, nor necessarily tied to genetic factors [10][11][12][13][14][15]. Comorbidities include immune dysregulation, [16][17][18][19][20][21][22][23] gastrointestinal issues such as diarrhea, constipation, and dysbiosis, mitochondrial dysfunction [24][25][26][27], poor detoxification [28], inflammation [29], food sensitivities, evidence of environmental toxicants [30][31][32][33][34][35][36][37][38][39][40][41][42], retained reflexes [43,44] and other structural or functional challenges. ...
The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990’s, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating reversal of autism diagnoses with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD “requiring very substantial support” at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin’s symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins’ symptoms, which was manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing environmental and lifestyle risk factors.
... ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; CI, confidence interval; HR, hazard ratio; IQR, interquartile range; SES, socioeconomic status. Hsu et al., 2007) and teeth (Adams et al., 2007) in ASD cases are higher than those in controls. Exposure to ambient heavy metals during the prenatal and postnatal periods in the development of ASD is still unclear due to the small study population, lack of longitudinal study design taking ambient air pollution may change over time into consideration, and high temporal and spatial resolution of exposure assessment, and an unascertained exposure period during the neurodevelopment time window (Modabbernia et al., 2017). ...
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders, and its incidence is increasing over time. Although several environmental factors have been suspected to be risk factors for ASD, studies on the effects of airborne heavy metals on newly developed ASD are still limited. We conducted a large birth cohort study of 168,062 live term births in Taichung during 2004-2011 to assess the association of heavy metals in particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) with ASD, and identify sensitive time windows during prenatal and postnatal periods. Heavy metals, including arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in PM2.5, were estimated using the Weather Research and Forecasting/Chem (WRF/Chem), inserted from the top 75 emission sources for the module. The association between childhood ASD and 4 metals were analyzed from pregnancy to 9 months after birth. The Cox proportional hazard model with a distributed lag nonlinear model (DLNM) was used to estimate the association between heavy metals in PM2.5 and ASD. We identified 666 incident ASD cases in 168,062 participants. A positive association between Hg and ASD was found at 9 months after birth (Hazard Ratio: 1.63; 95% CI: 1.13-2.36). According to the DLNM, there was an increased risk of exposure to Hg during 10-25 weeks after birth, and decreased risk of exposure to Hg during gestational weeks 4-6. Exposure to As and Hg on the risk of ASD were significantly stronger in low birth weight infants (<2500 g) than in those of birth weight ≥2500 g during postnatal period. Postnatal exposure to Hg in PM2.5 may associate with increased ASD incidence. Infants with low birth weight and exposure to As and Hg in PM2.5 are more likely to develop ASD.
... An animal experiment has shown that antibiotics can block the excretion of Hg, reduce the number As meta-analysis forest plot. of intestinal flora by demethylating methylmercury, and possibly increase the number of yeasts and escherichia coli by methylating inorganic mercury, thereby promoting mercury uptake and lowering mercury excretion (87). On the other hand, a lower level of glutathione and higher level of oxidative stress in ASD patients can also compromise mercury excretion, resulting in a heavier burden on the body (20). The present study demonstrates that it is necessary to reduce exposure to Hg, especially for pregnant women and children in brain-developing. ...
Background
Studies have found that toxic heavy metals exposure could induce the generation of reactive oxygen species (ROS), and is of epigenetic effect, which might be associated with the occurrence of Autistic Disorder (ASD). This systematic review and meta-analysis aims to elucidate the association between exposure to 4 heavy metals, cadmium (Cd), lead (Pb), arsenic(As), and mercury (Hg), and the occurrence of ASD in children.
Methods
We searched PubMed, Web of Science, Embase, and Cochrane Library, from their inception to October 2022, for epidemiological investigations that explore the association between exposure to Cd, Pb, As, or Hg and the occurrence of child ASD.
Results
A total of 53 studies were included, involving 5,054 individuals aged less than 18 (2,533 ASD patients and 2,521 healthy controls). Compared with the healthy controls, in hair and blood tests, concentrations of the 4 heavy metals were significantly higher in the ASD group than in the healthy control group, and the differences in Pb, arsenic and Hg were statistically significant ( P < 0.05). In the urine test, concentrations of arsenic and Hg were significantly higher in the ASD group than in the healthy control group ( P < 0.05), while the results of Cd and Pb were opposite to those of arsenic and Hg ( P > 0.05). Subgroup analysis for geographic regions showed that ASD patients in Asia and Europe had higher concentrations of the 4 heavy metals, compared with the healthy controls, in which the differences in Pb, arsenic, and Hg were statistically significant ( P < 0.05), while in North America, the healthy controls had higher Cd, arsenic, and Hg concentrations ( P > 0.05).
Conclusion
Compared with the healthy control group, the ASD group had higher concentrations of Cd, Pb, arsenic, and Hg. These 4 heavy metals play different roles in the occurrence and progression of ASD. Moreover, there is significant heterogeneity among the included studies due to controversies about the study results among different countries and regions and different sources of detection materials. The results of this study firmly support the policies to limit heavy metals exposure, especially among pregnant women and young children, so as to help reduce the incidence of ASD.
... Ten studies showed a positive association ( , and one study revealed a negative connection (Yorbik et al., 2010), and three studies indicated no relationships (Albizzati et al., 2012;Fuentes-Albero et al., 2015;Soden et al., 2007). Pb in teeth was analyzed in two studies, and no relationship was revealed (Abdullah et al., 2012;Adams et al., 2007). One study found a positive association between ASD and Pb exposure in the nail (Lakshmi Priya and Geetha, 2011). ...
Background and aim
Autism spectrum disorder (ASD) is a neurodevelopmental illness characterized by difficulties in social communication and repetitive behaviors. There have been many previous studies of toxic metals in ASD. Therefore, the priority of this study is to review the relationships between exposure to toxic metals and ASD.
Materials & methods
This study was based on a comprehensive search of international databases, such as Web of Science, Science Direct, Scopus, PubMed, and Google Scholar, for all works related to the subject under discussion from 1982 to 2022. We further summarize published data linked to this topic and discuss with clarifying evidence that agrees and conflicts with the association between exposure to toxic metals, including mercury (Hg), lead (Pb), cadmium (Cd), arsenic (As), and aluminum (Al) and ASD.
Results
40 out of 63 papers met the requirements for meta-analysis. Blood Pb levels (standardized mean difference (SMD) = 0.81; 95 % confidence interval (CI): 0.36–1.25), blood Hg (SMD = 0.90; CI: 0.30–1.49), hair Pb (SMD = 1.47; CI: 0.03–2.92), urine As (SMD = 0.65; CI: 0.22–1.09), and urine Al levels (SMD = 0.85; CI: 0.40–1.29) in autistic individuals were significantly higher than those of healthy control (HC). Whereas, blood As levels (SMD = 1.33; CI: −1.32–3.97), hair As (SMD = 0.55; CI: −0.14–1.24), hair Cd (SMD = 0.60; CI: −0.31–1.51), hair Hg (SMD = 0.41; CI: −0.30–1.12), hair Al (SMD = 0.87; CI: −0.02–1.77), urine Pb (SMD = −0.68; CI: −2.55–1.20), urine Cd (SMD = −0.26; CI: −0.94–0.41), and urine Hg levels (SMD = 0.47; CI: −0.09–1.04) in autistic individuals were significantly lower than those of HC.
Conclusion
Toxic metal content significantly differed between individuals with ASD and HC in the current meta-analysis. The results assist in clarifying the significance of toxic metals as environmental factors in the development of ASD.
... Environmental factors' significance implies that hazardous exposures may have an etiological role: either prenatally, postnatally, or in a cumulative pattern that incorporates the impacts of maternal, gestational, and newborn exposures [10]. ...
Autism is a severe developmental disease characterized by social disengagement, communication impairments, and repetitive/stereotypic behaviour. Although the pathophysiological etiologies of autism remain obscure and contentious in many cases, genetic and environmental variables (and their interactions) have been identified. While autism is recognized to have multiple causative reasons, ecological variables have gained considerable attention. The Global debate has centred on neurotoxins such as Mercury, Cobalt, and Aluminium, with some claiming that these and other toxic metals contribute to the disorder's development. The study is performed in Al-Anbar province (Iraq) between march to December 2020. Seventy-five autistic patients suffered from ASD characterized by DSM-V compared with twenty-five control. Heavy metals and trace element Mercury, aluminum, and cobalt in hair specimens are measured by atomic absorption spectrophotometer are shown as higher in Aluminium concentration in patients versus healthy Control, and Global Value, more than Aluminium contributed as environmental risk-factor for ASD, While the level of Cobalt is described high in children with autistic and slightly in healthy Control compare with Global Value. These results come from environmental contaminated in Iraq's. Additively, Mercury concentration is significantly higher in autistic patients than in Control. Still, the concentration of both autism and Control typical compared with Global Value and Mercury consider no-environmental risk-factor for Iraqi community’s.
... Increased Pb levels in hair samples of autistic children have been found by other authors (Fido and Al-Saad, 2005), while, Kern et al. presented statistically its lower levels (Kern et al., 2007). On the other hand, another study did not reveal significant differences in Pb levels in teeth (Adams et al., 2007) in children with autism and controls. Inappropriate concentrations of toxic metals might significantly increase the risk of ASD, however, which primarily concerns specific developmental periods (either pre-or postnatal) when individuals are more susceptible to the Abbreviations: Childhood Autism Rating Scale (CARS), glutathione-s-transferase (GST), Red Blood Cells (RBC), glutathione status (GSH/GSSG), glutathione reductase (GR), glutathione-s-transferase (GST), thioredoxin (Trx), thioredoxin reductase (TrxR), peroxidoxins (Prxs I and III), glutamate dehydrogenase (GDH), developmental delay (DD), pervasive developmental disorder (PDD), Antibody anti-maltose-binding protein (Anti-MBP), 3-nitrotyrosine (3-NT), healthy controls (HC). ...
The identification of biomarkers as diagnostic tools and predictors of response to treatment of neurological developmental disorders (NDD) such as schizophrenia (SZ), attention deficit hyperactivity disorder (ADHD), or autism spectrum disorder (ASD), still remains an important challenge for clinical medicine. Metallomic profiles of ASD patients cover, besides essential elements such as cobalt, chromium, copper, iron, manganese, molyb-denum, zinc, selenium, also toxic metals burden of: aluminum, arsenic, mercury, lead, beryllium, nickel, cad-mium. Performed studies indicate that children with ASD present a reduced ability of eliminating toxic metals, which leads to these metals' accumulation and aggravation of autistic symptoms. Extensive metallomic studies allow a better understanding of the importance of trace elements as environmental factors in the pathogenesis of ASD. Even though a mineral imbalance is a fact in ASD, we are still expecting relevant tests and the elaboration of reference levels of trace elements as potential biomarkers useful in diagnosis, prevention, and treatment of ASD.
... In addition, a large number of animal model studies have suggested that Zn deficiency may lead to the clinical features of ASD in rats or mice, including impairment in social behavior, impairment in learning and memory changes, and depression-like behavior, which enhanced the association between Zn deficiency and ASD [18]. However, some studies showed higher concentration of Zn in the ASD group or no significant difference between the two groups [3,4,28,40,44]. Besides the factors mentioned above which may lead to the inconsistent results, the age of the included subjects may also act as a confounding factor for Zn. ...
Essential metal elements (EMEs) have essential roles in neurological development and maintenance of human homeostasis. We performed a case-control study to explore association between the risk of autism spectrum disorder (ASD) and the 11 EMEs [Calcium (Ca), potassium (K), magnesium (Mg), sodium (Na), manganese (Mn), selenium (Se), cobalt (Co), Molybdenum (Mo), copper (Cu), zinc (Zn), and iron (Fe)] in serum. Ninety-two autistic subjects (cases) and age-sex-matched healthy subjects (controls = 91) from Beijing, China were recruited. In addition, totally 109 mothers of recruited children participated in this study. ICP-AES and ICP-MS were applied to determine the concentration of 11 EMEs in serum. The concentrations of Ca, K, and Mg were significantly higher in the cases than in the controls (OR [95% CI]: 1.031 [1.006–1.058] for Ca; 1.081 [1.046–1.118] for K; 1.161 [1.012–1.331] for Mg), while the concentrations of Zn and Cu were significantly lower (0.997 [0.995–0.999] for Cu; 0.996 [0.992–1.000] for Zn). Clear dose-response relationships between EMEs concentrations and the risk of ASD, as well as the correlation between EME concentrations and the severity of ASD were observed for most of the above EMEs. Six and seven specific correlated pairs between mothers and children were found in the cases and controls separately. The overall profiles of the EMEs were changed in the cases as compared to the controls. This study suggested that the higher levels of Ca, K, and Mg and lower levels of Zn and Cu may be associated with an elevated risk of ASD.
... There is a growing consensus among scientists and clinicians that ASDs ensue from an interaction between biological vulnerability factors and environmental or iatrogenic insults (Aicardi et al, 2009). This points to the importance of environmental factors and raises the possibility of an etiological role for toxic exposures: either prenatal, postnatal, or in some cumulative pattern that combines the effect of maternal, gestational, and infant exposures (Adams et al., 2007). ...
... The possible association between exposure to Hg and autism spectrum disorder (ASD) has been investigated in several studies and conflicting findings have been reported. For example, some studies have found that individuals with ASD had significantly higher Hg levels versus typically developing (TD) controls as measured by levels in hair [13][14][15][16], urine [17], red blood cells [18][19][20], whole blood [21][22][23][24], and baby teeth [25]. In contrast, other studies reported significantly lower Hg levels in ASD cases than TD controls as measured in hair [26][27][28][29], or no significant difference in the Hg level between ASD cases and TD controls as measured in whole blood [30][31][32][33][34][35][36][37], hair [31,34], and urine [33,34,[38][39][40]. ...
We investigated interactive roles of three metabolic glutathione S-transferase (GST) genes (GSTP1, GSTT1, and GSTM1) and autism spectrum disorder (ASD) status in relation to blood Hg concentrations (BHC) of Jamaican children. We used data from 266 children (2-8 years) with ASD and their 1:1 age- and sex-matched typically developing (TD) controls. After adjusting General Linear Models for child’s age, socioeconomic status, consumption of leafy vegetables, fried plantain, canned fish, and the interaction between GSTP1 and GSTT1, we found significant interactions between GSTP1 and ASD status in relation to BHC either in a co-dominant or dominant genetic model for GSTP1(P < 0.001, P = 0.007, respectively). In the co-dominant model for the Ile105Val GSTP1 polymorphism, geometric mean (GM) BHC in ASD cases with genotype Ile/Ile were significantly higher than in cases with the Ile/Val genotype (0.73 vs. 0.48 µg/L, P = 0.01). In contrast, in TD controls with the Ile/Val genotype GM BHC were significantly higher than in those with the Ile/Ile genotype (0.72 vs. 0.49 µg/L, P = 0.03) or the Val/Val genotype (0.72 vs. 0.51 µg/L, P = 0.04). Although our findings are consistent with the role of GSTP1 in detoxification of Hg, replication in other populations is warranted.
... 10 Mercury is considered as a risk factor for autism 4 since, according to previous studies, it has been recognized as a neurotrophic toxin. 11 Reduction in mercury content in hair 12 and teeth 13 of the children with autism aroused the low disposal of mercury hypothesis. Blaurock-Bush et al found that heavy metals are effective in the development of autism disorder. ...
Background and objectives:
There is a likelihood of a possible relationship between the concentrations of copper, lead, and mercury and autism. The present review was carried out to determine the relationship between the concentrations of these elements and autism by meta-analysis.
Methods:
In this study, searching Scopus, PubMed, and Science Direct databases, 18 articles conducted in different countries from 1982 to 2019 were collected. Studies' heterogeneity was investigated using the I2 index. The data were analyzed using R and STATA software.
Results:
In these 18 studies, 1797 patients (981 cases and 816 controls) aged 2 to 16 years were examined. Concentration of the samples (blood, hair, and nails) for both case and control groups was evaluated. There was no significant relationship between copper concentration and autism (SMD (95% CI): 0.02 (-1.16,1.20); I2=97.7%; P=0.972); there was a significant relationship between mercury concentration and autism (SMD (95% CI): 1.96 (0.56,3.35); I2=98.6%; P=0.006); there was also a significant relationship between lead concentration and autism (SMD (95% CI): 2.81 (1.64,3.98); I2=97.8%; P=0.000).
Conclusion:
There is, nevertheless, a significant relationship between mercury concentration and autism. Thus, the concentration of mercury can be listed as a pathogenic cause (disease-causing) for autism.
... El metil-mercurio, como agente químico industrial, ha sido relacionado con la etiopatogenia de los trastornos del neurodesarrollo (Grandjean y Landrigan, 2006) y durante las tres últimas décadas se han publicado numerosos estudios que investigan la asociación entre mercurio y autismo. La muestra del estudio CHARGE fue utilizada para comparar las concentraciones en sangre de mercurio entre sujetos con TEA y controles (Hertz-Picciotto et al., 2010); otros investigadores han determinado los niveles de mercurio en diferentes fluidos y tejidos corporales como la orina (Wright et al., 2010), el tejido cerebral (Khan et al., 2014), el pelo (Holmes et al., 2003) o los dientes (Adams et al., 2007), entre otros. Los trabajos actuales de revisión y meta-análisis en torno a este tema (Jafari et al., 2017;Kern et al., 2016) consideran que el mercurio es un importante factor causal en el autismo y sugieren que los mecanismos de detoxificación y excreción podrían estar alterados en estos sujetos, lo que conllevaría a una acumulación de esta sustancia en el organismo. ...
Introducción y objetivos. Dadas las limitaciones en el tratamiento de los Trastornos del Espectro Autista (TEA), muchas familias recurren al uso de intervenciones alternativas. La dieta libre de gluten y caseína (DLGC) como enfoque etiopatogénico y terapéutico de los TEA ha recibido abundante atención bibliográfica y sigue siendo actualmente objeto de interés y controversia. La beta-casomorfina es un péptido derivado de las proteínas de la leche de vaca, llamada así por su procedencia (caseína) y por su actividad opioide similar a la morfina. Se ha postulado que los sujetos con TEA podrían tener altas concentraciones de estos biopéptidos que influirían en el origen y en el curso de los síntomas nucleares y periféricos del autismo. Los objetivos de esta investigación son: 1) Determinar la influencia de una DLGC sobre las alteraciones del comportamiento de niños y adolescentes diagnosticados de TEA y 2) Estudiar la relación entre los posibles cambios conductuales y los niveles urinarios de beta-casomorfina.
Material y método. Se realizaron dos estudios de similares características pero con periodos de seguimiento diferentes, en diferentes momentos de tiempo y utilizando muestras distintas. Primero se realizó un estudio a 3 + 3 meses de seguimiento y años más tarde se replicó la metodología para un segundo estudio en el que se amplió la intervención a 6 + 6 meses. El tipo de diseño escogido para ambos estudios fue un ensayo clínico aleatorizado cruzado a simple ciego. El periodo de seguimiento se dividió en dos fases de la misma duración cada una (tres meses para el primer estudio y seis meses para el segundo). Cada participante recibió durante una fase dieta normal (con gluten y caseína) y durante la otra fase DLGC. Se asignó aleatoriamente el orden de intervención (empezar con dieta normal o DLGC) y se realizaron tres evaluaciones a lo largo del seguimiento (al inicio de cada estudio, tras la dieta normal y tras la DLGC). En cada evaluación se cumplimentaron cuestionarios de conducta y autismo, de seguimiento de la dieta y se determinaron los niveles de beta-casomorfina en orina.
Resultados. En ninguno de los dos estudios (3 + 3 meses y 6 + 6 meses) se encontraron cambios significativos en las escalas de conducta ni en los niveles urinarios de beta-casomorfina tras la DLGC.
Conclusiones. Una DLGC no produce cambios significativos en los síntomas comportamentales del autismo ni en los niveles urinarios de beta-casomorfina. Son necesarios futuros estudios que, además de eliminar el gluten y la caseína durante un periodo de tiempo suficiente (al menos 6 meses), incluyan elementos de placebo y doble ciego, así como otros marcadores biológicos para definir mejor a los sujetos que puedan beneficiarse de estas dietas.
... To the best of our knowledge, in deciduous teeth of children with ASD or ADHD, there have been only a handful of studies exploring element levels. Previously, teeth of children with ASD revealed two times higher levels of Hg but similar levels of Pb and Zn [12]. Also, tooth element levels in twins discordant for ASD were investigated and showed lower perinatal Mn levels, a drop in Zn levels during the prenatal period, and a marked increase postnatal and overall levels of Pb in the affected twin [13]. ...
Background
Environmental factors, including elemental homeostasis, have not been studied sufficiently in Neurodevelopmental Disorders (NDD). This study aims to compare the status of 13 elements in blood and deciduous teeth dentine of children having an autism spectrum disorder or attention deficit hyperactivity disorder with typically developing controls.
Methods
Elements including calcium, phosphorous, magnesium, iron, zinc, copper, chromium, manganese, mercury, lead, cadmium, molybdenum, and strontium in both deciduous teeth and blood were analyzed by inductively coupled plasma mass spectrometry.
Results
Strontium levels in both blood and teeth samples were found to be significantly lower in the NDD group. Additionally, blood cadmium and mercury levels, and copper/zinc ratio were higher in the NDD group.
Conclusions
Our results warrant further investigation in a large series of NDD examining symptom levels and genetic variations associated with elemental homeostasis.
... In this study, serum zinc levels were within the normal range of 70-120 μg/dl in all groups [52], and they were slightly higher in the groups of ASD, ADHD, and ASD-C groups with no significant value. Our study coincided with several previous studies that found no difference in serum zinc levels between ASD patients and controls [14,53]. Our results did not correspond with studies that found low levels of zinc in the children with ASD and ADHD compared with controls [15,54]. ...
Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are two developmental disorders that affect children worldwide, and are linked to both genetic and environmental factors. This study aims to investigate the levels of lead, manganese, and zinc in each of ASD, ADHD, and ASD with comorbid ADHD in Syrian children born or grown during the Syrian crisis. Lead and manganese were measured in the whole blood, and zinc was measured in the serum in 31 children with ASD, 29 children with ADHD, and 11 children with ASD with comorbid ADHD (ASD-C) compared with 30 healthy children, their ages ranged between 3 and 12 years. Blood lead levels were higher in the groups of ASD-C (245.42%), ASD (47.57%), and ADHD (14.19%) compared with control. Lead levels were significantly higher in children with ASD in the age of 5 or less compared with control, and they were also higher in the male ASD compared with females (P = 0.001). Blood manganese levels were lower in the groups of ASD-C (10.35%), ADHD (9.95%, P = 0.026), and ASD (9.64%, P = 0.046). However, serum zinc levels were within the reference range in all groups of study. Lead and manganese were positively correlated with each other (P = 0.01). Lead increase and manganese decrease may associate with the incidence of ASD, ADHD, or the co-occurrence of both of them together. Further studies are needed to examine the relationship between metal levels and the co-occurrence of ASD and ADHD together.
... Thus, higher use of oral antibiotics in the children is proposed to result in their reduced ability to excrete mercury. 7 So, average antibiotic usage in infancy was calculated by multiplying average number of episodes of illness with the average number of days of antibiotic days for each child. ...
Background: The role of heavy metals in the etio-pathogenesis of attention deficit hyperactivity disorder (ADHD) is a burning enigma. The available studies with discordant results are from different geographical localities with different monitoring, regulations and sociocultural backgrounds. The differential association of heavy metals with ADHD severity and phenotypes has not been adequately examined. Also, there are concerns about laboratory quality control. Therefore, the present case control study was formulated.Methods: Thirty children with ADHD diagnosed by DSM IV criteria and thirty group age matched controls were enrolled. Detailed perinatal, past, developmental and possible exposure history to various heavy metals was taken. Severity of ADHD was assessed using ConnersTM Parent reporting questionnaire. Blood level of metals was estimated by inductively coupled plasma- atomic emission spectroscopy (ICP-AES).Results: The mean blood lead, mercury, cadmium, arsenic, zinc were comparable in children with ADHD and group age matched controls. The mean blood lead, mercury and cadmium levels in study population was higher than found in studies from developed countries. Elevated arsenic, mercury and cadmium were found in both cases and controls. Blood zinc correlated significantly with inattention T score and blood mercury with hyperactivity-impulsitivity T score of Conners parent rating scale. Blood cadmium was present in greater proportion of predominant hyperactive-impulsive type patients.Conclusions: Zinc deficiency correlates with inattention; cadmium and mercury toxicity correlate with hyperactivity. Mean blood levels of heavy metals is elevated in a substantial proportion of study population. So, there is an urgent need for sensitization and environmental control.
... Our model proposes that teeth may serve as an additional, albeit novel, biomarker linking early-life psychosocial stress exposure to mental health risk ( Figure 2). Although this proposition has not yet been widely tested, recent work from at least eight studies on tooth-based markers of environmental toxins (e.g., pollutants, heavy metals) has provided some evidence that these physical exposures can be captured in teeth and used to predict risk for mental disorders such as schizophrenia and psychotic disorders (114,115), autism spectrum disorder (60,(116)(117)(118), and both internalizing and externalizing symptoms (119,120) ( Table 1). Whether toothbased markers of psychosocial stress can function as indicators of psychiatric risk will be a rich area of future inquiry. ...
Early-life adversity affects nearly half of all youths in the United States and is a known risk factor for psychiatric disorders across the life course. One strategy to prevent mental illness may be to target interventions toward children who are exposed to adversity, particularly during sensitive periods when these adversities may have even more enduring effects. However, a major obstacle impeding progress in this area is the lack of tools to reliably and validly measure the existence and timing of early-life adversity. In this review, we summarize empirical work across dentistry, anthropology, and archaeology on human tooth development and discuss how teeth preserve a time-resolved record of our life experiences. Specifically, we articulate how teeth have been examined in these fields as biological fossils in which the history of an individual's early-life experiences is permanently imprinted; this area of research is related to, but distinct from, studies of oral health. We then integrate these insights with knowledge about the role of psychosocial adversity in shaping psychopathology risk to present a working conceptual model, which proposes that teeth may be an understudied yet suggestive new tool to identify individuals at risk for mental health problems following early-life psychosocial stress exposure. We end by presenting a research agenda and discussion of future directions for rigorously testing this possibility and with a call to action for interdisciplinary research to meet the urgent need for new biomarkers of adversity and psychiatric outcomes.
Children's heightened susceptibility to environmental exposure arises from their underdeveloped detoxification mechanisms and augmented per-unit body-weight absorption capacity for chemical compounds. Primary teeth are an emerging biomatrix, which aid in storing crucial data on early exposure to harmful substances and developmental illnesses. This systematic review aimed to evaluate the association between environmental chemical exposure and health outcomes in children and adolescents using primary teeth as a matrix. The study protocol was registered with PROSPERO (CRD42023428013). The review spanned studies published between 1974 and 2023, identified through an extensive literature search on databases like MEDLINE, EMBASE, LILACS, CINAHL, the Cochrane Oral Health Group Specialized Register, Scopus, and Web of Science. Distiller SR software was used to assess study quality and extract the outcome data. The NTP-OHAT scale assessed evidence quality, and case-control, cross-sectional, and cohort studies in English were included. Comprehensively reviewing 5,287 articles resulted in 29 studies being included in the final analysis, comprising 15 cross-sectional, seven case-control, and seven cohort studies. All 29 studies qualified for qualitative analysis. Eleven studies analyzed lead (Pb) effects on health outcomes, four analyzed manganese (Mn), and 14 investigated other element groups. Primary teeth biomatrix assessed various health outcomes: neurobehavior, childhood behavior, ADHD, birth outcomes, fetal alcohol syndrome disease, inflammatory bowel disease, and dental caries. This study contributes to existing evidence, reinforcing a link between environmental metal exposure and health consequences. The evidence extends to prenatal and postnatal periods, substantiated by primary teeth biomatrix analysis. Lead level fluctuations can influence neuropsychological functioning, potentially causing cognitive impairments. Altered manganese levels correlate with behavioral issues, adverse effects on visuospatial development, and birth weight changes. Primary teeth biomatrices aid fetal alcohol spectrum disorders diagnosis, and correlations between organo-chemical exposure and autism were observed.
Autism spectrum disorder (ASD) is characterized by repetitive behaviors and deficits in social interaction. Its etiology is not completely clear, but both genetic and environmental factors contribute to and influence its development and course. The increased number of autism cases in recent years has been strongly associated with increased exposure to heavy metals. Mercury (Hg) has gained prominence in the scientific literature as a result of its presence as an urban pollutant and well‐described neurotoxicity. This review assessed the relationship between Hg exposure in the pre‐ and post‐natal period and ASD. The systematic review identified observational clinical studies and pre‐clinical trials in journals indexed in the PubMed, Embase, ProQuest, and LILACS databases. The aim of this study was to investigate the association between exposure to Hg and ASD and to define the critical period of exposure. A total of 57 articles were selected for this review, with 35 articles (61.40%) identifying a positive association between ASD and Hg, while 22 articles (38.60%) did not find the same outcome. The biological samples most used to analyze Hg body burdens were hair (36.84%) and blood (36.84%). Most case–control studies found an increase in Hg levels in individuals with ASD who were exposed to a polluted environment in the post‐natal period. Taken together, the studies suggest that these patients have a deficient detoxification system, and this could worsen the symptoms of the disorder. However, new studies addressing the influence of Hg on the post‐natal nervous system and its relationship with ASD should be carried out. image
Autism spectrum disorder is a group of neurodevelopmental disorders, characterized by presence of repetitive behavior/interests and problems in social communication/interactions. The number of individuals diagnosed with ASD each year are steadily increasing and has reached 1% i.e., one in every four individual is diagnosed with ASD. GWAS studies in the area, have confirmed a polygenic genotype of ASD, with several overlapping genes and phenotypical traits with other neurodevelopmental conditions. Twin studies in ASD indicate that genes alone are not responsible for occurrence or increased diagnosis of ASD. Instead, the environmental variables play a major role in neurodevelopmental outcomes and final diagnosis of ASD. This complex gene-environment interaction led researchers to look for etiologically meaningful environmental stressors that may pivot the diagnosis in favor of ASD. Out of the several stressors identified, this chapter focuses on chemical moieties as significant environmental variables influencing neurodevelopmental processes.
Over the last two decades, an emerging literature has focused on reporting how environmental factors (i.e., neurotoxins such as lead, phthalates, polychlorinated biphenyls (PCBs), and estrogen disruptors), may in part, contribute to the etiology of autism spectrum disorders (ASDs). Further, reports that investigated how these environmental factors induced oxidative stress to provide either acute neuroprotection or result in altered developmental neuropathology offer new insights on the mechanisms by which the brain can become hyperexcitable persisting beyond the GABA-shift. From such developmental neuropathological states, and careful evaluation of the shared glutathione-dependent neurobiological mechanisms between lead exposures and ASD, a sulfhydryl (SH)-dependent enzyme convergent relationship is observed. The physical chemistry between lead and sulfur compounds provides novel opportunities for reducing oxidative stress from metal exposures as chelating mechanisms to reduce metal toxicity. In ASD, similar reductions through (SH) groups are noted, and some populations with ASDs have metal exposures as a potential etiological factor. Thus, the present report highlights how SH compounds function as both neuroprotective and cytoprotective agents using a dynamic range of modifications that can occur with SH groups to mitigate stress in both ASD and lead poisoning. A particular SH compound, taurine, is explored in this context through its neuroprotective mechanisms using the glutathione pathway to stimulate future research to consider SH and/or taurine treatments of lead poisoning and ASDs as complimentary alternative medicines as nutraceuticals become more favorable treatment options in the twenty-first century.
The prevalence of autism spectrum disorder (ASD), a neurodevelopmental disorder with a predominance of social behavioral disorders, has increased dramatically in various countries in recent decades. The interplay between genetic and environmental factors is believed to underlie ASD pathogenesis. Recent analyses have shown that abnormal vitamin levels in early life are associated with an increased risk of autism. As essential substances for growth and development, vitamins have been shown to have significant benefits for the nervous and immune systems. However, it is unknown whether certain vitamin types influence the emergence or manifestation of ASD symptoms. Several studies have focused on vitamin levels in children with autism, and neurotypical children have provided different insights into the types of vitamins and their intake. Here, we review the mechanisms and significance of several vitamins (A, B, C, D, E, and K) that are closely associated with the development of ASD in order to prevent, mitigate, and treat ASD. Efforts have been made to discover and develop new indicators for nutritional assessment of children with ASD to play a greater role in the early detection of ASD and therapeutic remission after diagnosis.
Environmental pollutants, particularly toxic trace metals with neurotoxic potential, have been related to the genesis of autism. One of these metals that stands out, in particular, is lead (Pb). We conducted an in-depth systematic review and meta-analysis of peer-reviewed studies on Pb levels in biological materials retrieved from autistic children (cases) and neurotypical children (controls) in this work. A systematic review was conducted after the careful selection of published studies according to established criteria to gain a broad insight into the higher or lower levels of Pb in the biological materials of cases and controls, and the findings were then strengthened by a meta-analysis. The meta-analysis included 17 studies (hair), 13 studies (whole blood), and 8 studies (urine). The overall number of controls/cases was 869/915 (hair), 670/755 (whole blood), and 344/373 (urine). This meta-analysis showed significantly higher Pb levels in all three types of biological material in cases than in controls, suggesting a higher body Pb burden in autistic children. Thus, environmental Pb exposure could be related to the genesis of autism. Since no level of Pb can be considered safe, the data from this study undoubtedly point to the importance of regularly monitoring Pb levels in autistic children.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, the prevalence of which has increased in children and adolescents over the years. Studies point to deficiency of trace elements as one of the factors involved in the etiology of the disorder, with zinc being one of the main trace elements investigated in individuals with ASD. The aim of this review is to summarize scientific evidence about the relationship between zinc status and ASD in children and adolescents. This review has been registered in the International Prospective Register of Systematic Reviews (registration number CRD42020157907). The methodological guidelines adopted were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were selected from an active investigation of the PubMed, Scopus, LILACS, and Google databases to search for observational studies. Fifty-two studies from twenty-two countries were included. The sample sizes ranged from 20 to 2635, and the participants ranged from 2 to 18 years old. Nine types of biological matrices were used, with hair, serum, and plasma being the most frequently used in the evaluation of zinc concentrations. Significant differences in zinc concentrations between the ASD and control groups were observed in 23 studies, of which 19 (36%) showed lower zinc concentrations in the ASD group. The classification of studies according to methodological quality resulted in high, moderate, and low quality in 10, 21, and 21 studies, respectively. In general, we did not observe a significant difference between zinc concentrations of children and adolescents with ASD compared to controls; however, studies point to an occurrence of lower concentrations of Zn in individuals with ASD. This review reveals that more prospective studies with greater methodological rigor should be conducted in order to further characterize this relation.
Since genetic factors alone cannot explain most cases of Autism, the environmental factors are worth investigating as they play an essential role in the development of some cases of Autism. This research is a review paper that aims to clarify the role of the macro elements (MEs), Trace elements (TEs) and ultra-trace elements (UTEs) on human health if they are greater or less than the normal range. Aluminium (Al), cadmium Cd), lead (Pb), chromium (Cr), zinc (Zn), copper (Cu), nickel (Ni), arsenic (As), mercury (Hg), manganese (Mn), and iron (Fe) have been reviewed. Exposure to toxicants has a chemical effect that may ultimately lead to autism spectrum disorder (ASD). The Cr, As and Al are found in high concentrations in the blood of an autistic child when compared to normal child reference values. The toxic metals, particularly aluminium, are primarily responsible for difficulties in socialization and language skills disabilities. Zinc and copper are important elements in regulating the gene expression of metallothioneins (MTs), and zinc deficiency may be a risk factor for ASD pathogenesis. Autistics frequently have zinc deficiency combined with copper excess; as part of the treatment protocol, it is critical to monitor zinc and copper levels in autistic people, particularly those with zinc deficiency. Zinc deficiency is linked to epileptic seizures, which are common in autistic patients. Higher serum manganese and copper significantly characterize people who have ASD. Autistic children have significantly decreased lead and cadmium in urine, whereas they have significantly higher urine Cr. A higher level of As and Hg was found in the ASD individual's blood.
Maternal antibiotic (ABx) exposure can significantly perturb the transfer of microbiota from mother to offspring, resulting in dysbiosis of potential relevance to neurodevelopmental disorders such as autism spectrum disorder (ASD). Studies in rodent models have found long‐term neurobehavioral effects in offspring of ABx‐treated dams, but ASD‐relevant behavior during the early preweaning period has thus far been neglected. Here, we exposed C57BL/6J mouse dams to ABx (5 mg/ml neomycin, 1.25 μg/ml pimaricin, .075% v/v acetic acid) dissolved in drinking water from gestational day 12 through offspring postnatal day 14. A number of ASD‐relevant behaviors were assayed in offspring, including ultrasonic vocalization (USV) production during maternal separation, group huddling in response to cold challenge, and olfactory‐guided home orientation. In addition, we obtained measures of thermoregulatory competence in pups during and following behavioral testing. We found a number of behavioral differences in offspring of ABx‐treated dams (e.g., modulation of USVs by pup weight, activity while huddling) and provide evidence that some of these behavioral effects can be related to thermoregulatory deficiencies, particularly at younger ages. Our results suggest not only that ABx can disrupt microbiomes, thermoregulation, and behavior, but that metabolic effects may confound the interpretation of behavioral differences observed after early‐life ABx exposure.
Food is an essential component for reinforcing the physical and mental health of an individual. Balanced nutrients are essential for normal body functions. Micronutrients such as vitamins (Vitamin-A, B12, B6, folate), minerals (iron, magnesium), and omega fatty acids have a crucial role in cognitive and neuronal function, as well as amelioration of neurological disorders. The production and storage capability of micronutrients inside the body decreases with age, and it needs to be supplemented externally through the diet. In contrast, the absence of micronutrients in the body leads to various neurological disorders. Pharmacological interventions for treating neurological disorders are restricted and are correlated with a notable risk of adverse events. Diet predominantly with micronutrient supplementation is recommended as a safe and effective way for ameliorating neurological disorders. Studies with supplementation of micronutrients have evolved from single-use vitamin/mineral to broad-spectrum micronutrients (BSM) in the ministration of neurological disorders. Suboptimal nutrition is the key to mental illness, and multi-micronutrient supplementation in addition to food intake could improve symptoms associated with neurological disorders. This chapter explains the importance of micronutrients in neurological development, the combination of micronutrient effects, recent studies on neurological disorders, improvements observed with single micronutrient supplementation, multi-nutrient supplementation, and also neuro-toxic effects of some heavy metals.KeywordsMicronutrientsNeurological disordersSingle-use micronutrientsBroad-spectrum-micronutrientsHeavy metals
Mercury occurs as elemental mercury and as inorganic and organic compounds (mercury vapor, mercury liquid, mercury salts, short-chain alkylmercury compounds, alkoxyalkylmercury compounds, and phenylmercury compounds), all with different toxicological properties. Total mercury can be analyzed in water, air, and biological material by cold vapor atomic absorption methods and by neutron activation analysis and can be detected down to concentrations of a 10th of a nanogram per gram in biological material. Methylmercury (MeHg) can be detected in biological material at levels of a few nanograms by extraction with benzene after strong acidification with hydrochloric acid, followed by gas chromatographic analysis of MeHg chloride. Other analytical methods for speciating inorganic mercury and several of the organomercurial forms have also been published. These methods include isotope dilution mass spectrometry, time-of-flight mass spectrometry, high-performance liquid chromatography inductively coupled plasma (ICP) mass spectrometry, capillary electrophoresis-ICP, gas chromatography-ICP, and X-ray absorption fine structure spectroscopy.
Mercury is circulated naturally in the biosphere, with 5500 metric tons (t) being released into the atmosphere by degassing from the Earth's crust and the oceans. In addition, 2500 t of mercury are released into the environment each year through human activities such as the combustion of fossil fuels and other industrial releases. Approximately 2000 tons of mercury per year is produced for industrial use, a small part of which is used for synthesizing organic mercury compounds. The world production of mercury for commercial uses has been slowly declining over the past 20 years. There is now a ban on the export of mercury from the European Union and the United States.
In nature, MeHg is produced from inorganic mercury as a consequence of microbial activity. In mammals, oxidative demethylation occurs in vivo to produce inorganic mercury. In fish, most mercury is present as MeHg. Factors determining the MeHg concentration in fish are the mercury content in water and bottom sediments, the pH and redox potential of water, and the species, age, and size of the fish.
The toxic properties of mercury vapor are a consequence of mercury accumulation in the brain causing neurological signs involving an unspecific psychasthenic and vegetative syndrome (micromercurialism). At high exposure levels, mercurial tremor is seen, accompanied by severe behavioral and personality changes, increased excitability, loss of memory, and insomnia. Mercurials may also affect other organ systems, such as the kidney. On a group basis, exposure levels are likely to be reflected by mercury concentrations in the blood and urine. Occupational exposure to mercury concentrations in air of >0.1 mg/m³ may produce mercurialism. Micromercurialism has not been reported at concentrations <0.01 mg/m³. Exposure to mercury vapor inhibits brain development in primates and in humans with certain genotypes. The exact dose–response relationship in humans is not known. Inorganic mercury, but not MeHg, has been found to induce and bind to the low molecular weight metal-binding protein, metallothionein.
The acute and long-term actions of mercuric salts, phenylmercury compounds, and alkoxyalkylmercury compounds are likely to be gastrointestinal disturbance and renal damage appearing as tubular dysfunction, with tubular necrosis in severe cases. The lethal dose in humans is approximately 1 g mercuric salt. The mercury load on the kidney is best determined by analysis of renal biopsy. Mercury concentrations in the kidney of between 10 and 70 mg/kg have been reported in poison cases with renal injury. Levels <3 mg/kg may be found in normal cases. Occasionally, mercuric compounds may cause idiosyncratic skin symptoms, which may develop into severe exfoliative dermatitis or cause glomerular nephritis. Animal and clinical observations have shown that mercuric mercury stimulates and MeHg inhibits the immune system. A specific form of idiosyncrasy, called acrodynia or pink disease, is seen in children. Most cases are associated with mercury exposure in which increased levels of mercury in urine are detected.
Hazards involved in the long-term intake of food containing MeHg or ethylmercury (EthylHg) and in occupational exposure to MeHg are a result of the efficient absorption (90%) of alkylmercury in humans and the long retention time (half-life of 70 days for MeHg and shorter for EthylHg) leading to accumulation of alkylmercury in the brain. Chronic poisoning results in degeneration and atrophy of the sensory cerebral cortex, paresthesia, ataxia, hearing, and visual impairment, and an increased risk for cardiovascular diseases such as myocardial infarction and stroke. The latter effects are attenuated by the intake of polyunsaturated fatty acids (PUFAs) through fish consumption. Prenatal exposure causes cerebral palsy and, in less severe cases, psychomotor retardation. MeHg concentration in the blood and hair reflects the body burden and the brain concentration of MeHg. Intake resulting in body burdens of <0.5 mg/kg body weight is not likely to give rise to detectable neurological signs in adults. This intake corresponds to blood values of <200 μg/L and mercury levels in the hair of <50 mg/kg. However, this level of MeHg exposure in pregnant women may result in inhibited brain development of the fetus, with psychomotor retardation of the child. This effect also appears to be reduced by the intake of PUFAs through fish consumption. The highest level of MeHg load in pregnant women that is not associated with inhibition of fetal brain development is not known. Recent epidemiological studies have revealed that genetic polymorphisms can modify mercury metabolism and susceptibility to mercury exposure. Specific genotypes have been associated with increased susceptibility to mercury exposure in humans.
Bisphenol A (BPA) is an environmental risk factor for autism spectrum disorder (ASD). BPA exposure dysregulates ASD-related genes in the hippocampus and neurological functions of offspring. However, whether prenatal BPA exposure has an impact on genes in the prefrontal cortex, another brain region highly implicated in ASD, and through what mechanisms have not been investigated. Here, we demonstrated that prenatal BPA exposure disrupts the transcriptome–interactome profiles of the prefrontal cortex of neonatal rats. Interestingly, the list of BPA-responsive genes was significantly enriched with known ASD candidate genes, as well as genes that were dysregulated in the postmortem brain tissues of ASD cases from multiple independent studies. Moreover, several differentially expressed genes in the offspring’s prefrontal cortex were the targets of ASD-related transcription factors, including AR, ESR1, and RORA. The hypergeometric distribution analysis revealed that BPA may regulate the expression of such genes through these transcription factors in a sex-dependent manner. The molecular docking analysis of BPA and ASD-related transcription factors revealed novel potential targets of BPA, including RORA, SOX5, TCF4, and YY1. Our findings indicated that prenatal BPA exposure disrupts ASD-related genes in the offspring’s prefrontal cortex and may increase the risk of ASD through sex-dependent molecular mechanisms, which should be investigated further.
Metal dyshomeostasis plays a significant role in various neurological diseases such as Alzheimer’s disease, Parkinson’s disease, Autism Spectrum Disorders (ASD), and many more. Like studies investigating the proteome, transcriptome, epigenome, microbiome, etc., for years, metallomics studies have focused on data from their domain, i.e., trace metal composition, only. Still, few have considered the links between other “omes,” which may together result in an individual’s specific pathologies. In particular, ASD have been reported to have multitudes of possible causal effects. Metallomics data focusing on metal deficiencies and dyshomeostasis can be linked to functions of metalloenzymes, metal transporters, and transcription factors, thus affecting the proteome and transcriptome. Furthermore, recent studies in ASD have emphasized the gut-brain axis, with alterations in the microbiome being linked to changes in the metabolome and inflammatory processes. However, the microbiome and other “omes” are heavily influenced by the metallome. Thus, here, we will summarize the known implications of a changed metallome for other “omes” in the body in the context of “omics” studies in ASD. We will highlight possible connections and propose a model that may explain the so far independently reported pathologies in ASD.
Autism spectrum disorder (ASD) is a common childhood neurodevelopmental disorder that may be related to trace elements. However, reports on the relationship between them are still inconsistent. In this article, we conducted a meta-analysis on this issue. We searched the PubMed, EMBASE, and Cochrane databases as of November 15, 2019. A random-effects model was used, and subgroups of studies were analyzed using samples of different measurements. Twenty-two original articles were identified (18 trace elements, including a total of 1014 children with ASD and 999 healthy controls). In autistic children, the overall levels of barium (Ba), mercury (Hg), lithium (Li), and lead (Pb) were higher. There were significant differences in the levels of copper (Cu) in the hair and serum between autistic children and the control group. The levels of Hg, Li, Pb and selenium (Se) in the hair of autistic children were higher than those of healthy children, while the levels of zinc (Zn) in the blood were lower. Excessive exposure to toxic heavy metals and inadequate intake of essential metal elements may be associated with ASD. Preventing excessive exposure to toxic metals and correcting poor dietary behaviors may be beneficial for the prevention and treatment of the disease.
The consumption of food products containing the non-caloric sweetener aspartame
has increased since the 80’s, when these products were introduced in the market. Since
then, several pieces of evidence suggest that aspartame may be potentially harmful
to the nervous system, although some controversy on this subject still persists. Some
research suggests an association between aspartame intake and metabolic damage to
the central nervous system (CNS), such as changes in enzyme and neurotransmitter
activities. Considering the possible adverse neuronal actions of aspartame, we consider
it important to study the biological effects of this sweetener on the functional aspects
of the CNS. Objective: To analyze the pertinent literature on important aspects of the
possible neurophysiological alterations associated with aspartame consumption. Methods: We conducted a search for studies, whose strategy was developed for Embase,
Medline, Lilacs and Pubmed databases, according to the descriptors: Aspartame, brain
function and nervous system. We present here a narrative review of the literature over
the period from 1992 to 2012. Conclusion: experimental and clinical studies indicate the
risk of neural adverse reactions, which are associated with the use of aspartame, even
in relatively low doses. This risk might be higher in developing organisms. Because of
such evidence we recommend that the sweetener consumption, if any, should be performed with moderation and caution, under the guidance of a nutritionist or a medical
doctor, in order to avoid aspartame-associated deleterious effects on brain function,
mainly in children.
Background
Exposure to many environmental chemicals, including metals, often does not occur in isolation, hence requires assessment of the associations between exposure to mixtures of chemicals and human health.
Objectives
To investigate associations of a metal mixture of lead (Pb), mercury (Hg), arsenic (As), cadmium (Cd), manganese (Mn), and aluminum (Al) in children with autism spectrum disorder (ASD), additively or interactively with each of three glutathione S-transferase (GST) genes (GSTP1, GSTT1, and GSTM1).
Method
Using data from 266 case-control pairs of Jamaican children (2–8 years old), we fitted negative and positive generalized weighted quantile sum (gWQS) regression models to assess the aforementioned associations.
Results
Based on additive and interactive negative gWQS models adjusted for maternal age, parental education, child’s parish, and seafood consumption, we found inverse associations of the overall mixture score with ASD [MOR (95 % CI) = 0.70 (0.49, 0.99); P < 0.05) and [MOR (95 % CI) = 0.46 (0.25, 0.84); P = 0.01], respectively. In an unadjusted negative gWQS model, we found a marginally significant interaction between GSTP1 and a mixture of three metals (Pb, Hg, and Mn) (P = 0.07) while the association was no longer significant after adjustment for the same covariates (P = 0.24).
Conclusions
Differences in diet between ASD and control groups may play a role in the inverse associations we found. The possible interactive association between Mn and GSTP1 in ASD based on gWQS is consistent with our previous reports. However, possible interaction of GSTP1 with Pb and Hg in ASD requires further investigation and replication.
Autism spectrum disorder (ASD) is a complex neurobehavioral disorder that is believed to be multifactorial in origin. As the incidence of ASD is rising along with industrialization, and because certain metals have been linked to neurological problems, it is important to consider whether such metals may play a role in the development of ASD. Previously, we performed a meta-analysis of existing literature to examine the potential link between inorganic arsenic and lead exposure and ASD. This is a continuation of that study investigating the association of the exposure to aluminum (Al), cadmium (Cd), and mercury (Hg) and ASD. These metals were chosen because they are abundant in our environment, are known to cause neurological problems in humans, and have multiple published studies examining their potential links with ASD. Following the same approach as our previous paper, we conducted a systematic review of the existing literature and performed a meta-analysis to evaluate the current evidence regarding these metals and their potential relationship with autism. We reviewed 18 studies on Al, 18 on Cd, and 23 on Hg, and the individual studies showed inconsistent results. When the measurements were integrated into the meta-analysis, we found significant associations between all the metals and ASD, but the associations were not always in the same direction. Levels of Hg in hair, urine, and blood were all positively associated with ASD. Levels of Al in hair and urine were positively associated with ASD while levels of Al in blood were negatively associated. In comparison, levels of Cd in hair and urine were negatively associated with ASD. These results imply that, while these metals are all neurotoxic, their impact on the development of ASD and their modes of action could be different. Further researches are warrant to examine the longitudinal effects of these toxic metals on the risk of ASD, to assess the critical period when exposure may affect development, and to investigate potential factors that may enhance or ameliorate the effect of metals. Overall, these findings support policies that advocate limiting exposure to neurotoxic metals, particularly for pregnant women and young children, in order to help reduce the rising incidence of ASD.
Altered gut microbial profiles have been reported in humans with ASD and several rodent models of ASD, including BTBR mice, mice with maternal immune activation, maternal valproic acid exposure, and mice with mutations in Shank3. Maternal zinc deficiency also results in altered microbiota composition and an associated increase in proinflammatory markers. Thus, genetic and nongenetic factors in ASD show, apart from a shared synaptic pathology, shared extracerebral influences that ultimately may affect brain development and function through the so-called microbiota–gut–brain-axis. Therefore, the gastrointestinal tract is another tissue where abnormal trace metal status may provide another mechanistic link to explain its contribution to the etiology of ASD. The most recent findings will be highlighted in this chapter, in particular, in light of the transmission of the maternal microbiome to the offspring.
Metals have been known to influence the physiology of our body since hundreds of years. Therefore, they have not only been explored as a treatment for various diseases but also used as poisons to end lives. However, despite some apparent effects of acute deficiency or excess of some metals, the association of abnormal metal levels with neuropsychiatric disorders such as schizophrenia and neurodevelopmental disorders such as ASD is a quite recent discovery. Here, we will highlight the reasons for the short history of metal abnormalities as a risk factor for ASD and discuss the initial findings that lead to the most recent studies.
The Pharmacy One TM Poising Call Center (P 1 PCC), located in Amman, Jordan, was created to address deficiencies identified by the pharmacy service, including in the management of poisoning cases. The aims of this study were to analyze the patterns of poisoning cases reported to the P 1 PCC and to describe the role of the P 1 PCC pharmacist in ensuring preparedness and managing the response to poisoning cases. In addition, the information from these interventions was used to survey human poisoning in Jordan. This is a retrospective descriptive study of acute poisoning incidents in the Jordanian population, as recorded by the P 1 PCC during the period 2014-2018. Inquiries received by the P 1 PCC were recorded on a predesigned form. The year, patient demographics, toxic agent involved, and circumstances of the poisoning event were all fully documented utilizing Oracle and Excel spreadsheets. A total of 1,992 poisoning incidents were reported to the P1PCC, predominately (68.59%) via 911 phone calls. Reports were predominantly from males (1.67:1). Children were the second most common age group after adolescents (22.62% and 42.49%, respectively). The most frequent causative non-pharmaceutical agents were household products (17%) in preschool children and animal bites (20%) in adolescents. Most of the poisoning incidents (74.63%) occurred at home. Unintentional poisoning (54.12%), with mild medical outcomes (61.45%), accounted for most of the poisoning incidents caused by exposure to household products. These data may represent the most recent picture of poisoning incidents in Jordan. Emergency medical services were provided by experienced pharmacy practitioners at the P 1 PCC, to respond to emergency needs in the community in a professional manner. Therefore, the need for unnecessary hospitalization and the cost of ambulance dispatch were minimized, which are highly valuable outcomes.
The scientific literature often uses terms such as “limbic structures” or “limbic system” to describe regions of the nervous system that participate in emotional pro- cesses. Nonetheless, these concepts have been thoroughly revised over the last 150 years and there is no clear consensual definition for which regions are actually “lim- bic” or otherwise. This chapter will summarize the evolution of the concept of a limbic system and discuss the main neural structures that are credited as taking part in the elaboration and perception of emotional states.
Keywords: Limbic system, emotions, large scale brain networks.
In grappling for ways to respond to existence within permanently polluted worlds, this article asks: what does it mean to be good food for others? Where do all the chemicals and heavy metals go? What are the distributed effects? How might we hack legacies of toxic inheritance? What alternative practices and values are needed? This article explores the ways in which artists complicate death/food relations and nourishment through their express acknowledgement of chemically burdened bodies. In doing so, it draws on and extends Val Plumwood’s analytic of viewing humans as ‘being prey’ in the context of a feminist ethics of care and what Maria Puig de la Bellacasa refers to as ‘more caring affective ecologies’. Ultimately, it suggests that speculating on becoming prey and wanting to be good food for others – whether this is for a crocodile, fish, mushrooms or microbes in the soil – can propose new ways of configuring our relationships with human and more-than-human others in terms of toxicity and care.
Large autism epidemics have recently been reported in the United States and the United Kingdom. Emerging epidemiologic evidence and biologic plausibility suggest an association between autistic spectrum disorders and mercury exposure. This study compares mercury excretion after a three-day treatment w ith a n o ral c helating a gent, m eso-2,3- dimercaptosuccinic acid (DMSA), in children with autistic spectrum disorders and a matched control population. Overall, urinary mercury concentrations were significantly higher in 221 children with autistic spectrum disorders than in 18 normal controls (Relative Increase (RI)=3.15; P < 0.0002). Additionally, vaccinated cases showed a significantly higher urinary mercury concentration than did vaccinated controls (RI=5.94; P < 0.005). Similar urinary mercury concentrations were observed among matched vacci- nated and unvaccinated controls, and no association was found between urinary cadmium or lead concentrations and autistic spectrum disorders. The observed urinary concentrations of mercury could plausibly have resulted from thimerosal in childhood vaccines, although other environmental sources and thimerosal in Rh (D) immune globulin administered to mothers may be contributory. Regardless of the mechanism by which children with autistic spectrum disorders have high urinary mercury concentrations, the DMSA treatment described in this study might be useful to diag- nose their present burden of mercury.
We were initially highly skeptical that differences in the concentrations of thimerosal in vaccines would have any effect on the incidence rate of neurodevelopmental disorders after childhood immunization. This study presents the first epidemiologic evidence, based upon tens of millions of doses of vaccine administered in the United States, that associates increasing thimerosal from vaccines with neurodevelopmental disorders. Specifically, an analysis of the Vaccine Adverse Events Reporting System (VAERS) database showed statistical increases in the incidence rate of autism (relative risk [RR] = 6.0), mental retardation (RR = 6.1), and speech disorders (RR = 2.2) after thimerosal-containing diphtheria, tetanus, and acellular pertussis (DTaP) vaccines in comparison with thimerosal-free DTaP vaccines. The male/female ratio indicated that autism (17) and speech disorders (2.3) were reported more in males than females after thimerosal-containing DTaP vaccines, whereas mental retardation (1.2) was more evenly reported among male and female vaccine recipients. Controls were employed to determine if biases were present in the data, but none were found. It was determined that overall adverse reactions were reported in similar-aged populations after thimerosal-containing DTaP (2.4 +/- 3.2 years old) and thimerosal-free DTaP (2.1 +/- 2.8 years old) vaccinations. Acute control adverse reactions such as deaths (RR = 1.0), vasculitis (RR = 1.2), seizures (RR = 1.6), ED visits (RR = 1.4), total adverse reactions (RR = 1.4), and gastroenteritis (RR = 1.1) were reported similarly after thimerosal-containing and thimerosal-free DTaP vaccines. An association between neurodevelopmental disorders and thimerosal-containing DTaP vaccines was found, but additional studies should be conducted to confirm and extend this study.
Varicella breakthrough, the occurrence of varicella disease >42 days after vaccination, is indicative of vaccination failure. A sevenfold increased risk of breakthrough among vaccinated children with asthma was observed in a 1996 varicella outbreak in a child care center. More recent outbreak investigations have also identified age at vaccination as a potential risk factor for breakthrough. We assessed the association of varicella breakthrough with asthma, steroids, age at varicella vaccination, and timing of measles-mumps-rubella (MMR) vaccination.
We performed a retrospective cohort study among children born after 1993 and followed up through 1999 at 2 health maintenance organizations ([HMOs] A and B) in the United States. Information was obtained from automated vaccination, clinic, hospital discharge, and pharmacy records.
We identified 268 and 97 breakthrough cases among 80 584 and 8181 children vaccinated against varicella at HMOs A and B, respectively. Varicella breakthrough was not associated with asthma, inhaled steroids prescribed at any time, and oral steroids prescribed before vaccination. An increased risk of varicella breakthrough was found in the 3 months immediately after prescription for oral steroids at HMO A (adjusted relative risk [aRR]: 2.4; 95% confidence interval [CI]: 1.3-4.4) and HMO B (aRR: 2.8; 95% CI: 1.0-7.8), when varicella vaccine was given before 15 months of age at HMO A (aRR: 1.4; 95% CI: 1.1-1.9), and when varicella vaccination followed MMR vaccine within 28 days at HMO A (aRR: 3.1; 95% CI: 1.5-6.4).
Varicella vaccine failure in children was not associated with asthma or the use of inhaled steroids, but with the use of oral steroids. Administration of varicella vaccine before the age of 15 months may be associated with a slightly increased risk of breakthrough disease. As currently recommended, varicella vaccination should not be administered for 28 days after MMR vaccination.
Reported rates of autism have increased sharply in the United States and the United Kingdom. One possible factor underlying these increases is increased exposure to mercury through thimerosal-containing vaccines, but vaccine exposures need to be evaluated in the context of cumulative exposures during gestation and early infancy. Differential rates of postnatal mercury elimination may explain why similar gestational and infant exposures produce variable neurological effects. First baby haircut samples were obtained from 94 children diagnosed with autism using Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) criteria and 45 age- and gender-matched controls. Information on diet, dental amalgam fillings, vaccine history, Rho D immunoglobulin administration, and autism symptom severity was collected through a maternal survey questionnaire and clinical observation. Hair mercury levels in the autistic group were 0.47 ppm versus 3.63 ppm in controls, a significant difference. The mothers in the autistic group had significantly higher levels of mercury exposure through Rho D immunoglobulin injections and amalgam fillings than control mothers. Within the autistic group, hair mercury levels varied significantly across mildly, moderately, and severely autistic children, with mean group levels of 0.79, 0.46, and 0.21 ppm, respectively. Hair mercury levels among controls were significantly correlated with the number of the mothers' amalgam fillings and their fish consumption as well as exposure to mercury through childhood vaccines, correlations that were absent in the autistic group. Hair excretion patterns among autistic infants were significantly reduced relative to control. These data cast doubt on the efficacy of traditional hair analysis as a measure of total mercury exposure in a subset of the population. In light of the biological plausibility of mercury's role in neurodevelopmental disorders, the present study provides further insight into one possible mechanism by which early mercury exposures could increase the risk of autism.
It has been suggested that thimerosal, a mercury-containing preservative in vaccines, is a risk factor for the development of autism. We examined whether discontinuing the use of thimerosal-containing vaccines in Denmark led to a decrease in the incidence of autism.
Analysis of data from the Danish Psychiatric Central Research Register recording all psychiatric admissions since 1971, and all outpatient contacts in psychiatric departments in Denmark since 1995.
All children between 2 and 10 years old who were diagnosed with autism during the period from 1971-2000.
Annual and age-specific incidence for first day of first recorded admission with a diagnosis of autism in children between 2 and 10 years old.
A total of 956 children with a male-to-female ratio of 3.5:1 had been diagnosed with autism during the period from 1971-2000. There was no trend toward an increase in the incidence of autism during that period when thimerosal was used in Denmark, up through 1990. From 1991 until 2000 the incidence increased and continued to rise after the removal of thimerosal from vaccines, including increases among children born after the discontinuation of thimerosal.
The discontinuation of thimerosal-containing vaccines in Denmark in 1992 was followed by an increase in the incidence of autism. Our ecological data do not support a correlation between thimerosal-containing vaccines and the incidence of autism.
Mercuric compounds are nephrotoxic and neurotoxic at high doses. Thimerosal, a preservative used widely in vaccine formulations, contains ethylmercury. Thus it has been suggested that childhood vaccination with thimerosal-containing vaccine could be causally related to neurodevelopmental disorders such as autism.
To determine whether vaccination with a thimerosal-containing vaccine is associated with development of autism.
Population-based cohort study of all children born in Denmark from January 1, 1990, until December 31, 1996 (N = 467 450) comparing children vaccinated with a thimerosal-containing vaccine with children vaccinated with a thimerosal-free formulation of the same vaccine.
Rate ratio (RR) for autism and other autistic-spectrum disorders, including trend with dose of ethylmercury.
During 2 986 654 person-years, we identified 440 autism cases and 787 cases of other autistic-spectrum disorders. The risk of autism and other autistic-spectrum disorders did not differ significantly between children vaccinated with thimerosal-containing vaccine and children vaccinated with thimerosal-free vaccine (RR, 0.85 [95% confidence interval [CI], 0.60-1.20] for autism; RR, 1.12 [95% CI, 0.88-1.43] for other autistic-spectrum disorders). Furthermore, we found no evidence of a dose-response association (increase in RR per 25 microg of ethylmercury, 0.98 [95% CI, 0.90-1.06] for autism and 1.03 [95% CI, 0.98-1.09] for other autistic-spectrum disorders).
The results do not support a causal relationship between childhood vaccination with thimerosal-containing vaccines and development of autistic-spectrum disorders.
The prevalence of autism in the US has risen from 1 in approximately 2500 in the mid-1980s to 1 in approximately 300 children in the mid-1990s. The purpose of this study was to evaluate whether mercury from thimerosal in childhood vaccines contributed to neurodevelopmental disorders. Neurodevelopmental disorder dose-response curves for increasing mercury doses of thimerosal in childhood vaccines were determined based upon examination of the Vaccine Adverse Events Reporting System (VAERS) database and the 2001 US' Department of Education Report. The instantaneous dosage of mercury children received in comparison to the Food and Drug Administration (FDA)'s maximum permissible dose for the oral ingestion of methylmercury was also determined. The dose-response curves showed increases in odds ratios of neurodevelopmental disorders from both the VAERS and US Department of Education data closely linearly correlated with increasing doses of mercury from thimerosal-containing childhood vaccines and that for overall odds ratios statistical significance was achieved. Similar slopes and linear regression coefficients for autism odds ratios in VAERS and the US Department of Education data help to mutually validate each other. Controls employed in the VAERS and US Department of Education data showed minimal biases. The evidence presented here shows that the occurrence of neurodevelopmental disorders following thimerosal-containing childhood vaccines does not appear to be coincidental.
To assess the possible toxicity of thimerosal-containing vaccines (TCVs) among infants.
A 2-phased retrospective cohort study was conducted using computerized health maintenance organization (HMO) databases. Phase I screened for associations between neurodevelopmental disorders and thimerosal exposure among 124 170 infants who were born during 1992 to 1999 at 2 HMOs (A and B). In phase II, the most common disorders associated with exposure in phase I were reevaluated among 16 717 children who were born during 1991 to 1997 in another HMO (C). Relative risks for neurodevelopmental disorders were calculated per increase of 12.5 micro g of estimated cumulative mercury exposure from TCVs in the first, third, and seventh months of life.
In phase I at HMO A, cumulative exposure at 3 months resulted in a significant positive association with tics (relative risk [RR]: 1.89; 95% confidence interval [CI]: 1.05-3.38). At HMO B, increased risks of language delay were found for cumulative exposure at 3 months (RR: 1.13; 95% CI: 1.01-1.27) and 7 months (RR: 1.07; 95% CI: 1.01-1.13). In phase II at HMO C, no significant associations were found. In no analyses were significant increased risks found for autism or attention-deficit disorder.
No consistent significant associations were found between TCVs and neurodevelopmental outcomes. Conflicting results were found at different HMOs for certain outcomes. For resolving the conflicting findings, studies with uniform neurodevelopmental assessments of children with a range of cumulative thimerosal exposures are needed.
The purpose of the study was to evaluate the effects of MMR immunization and mercury from thimerosal-containing childhood vaccines on the prevalence of autism.
Evaluations of the Biological Surveillance Summaries of the Centers for Disease Control and Prevention (CDC), the U.S. Department of Education datasets, and the CDC's yearly live birth estimates were undertaken
It was determined that there was a close correlation between mercury doses from thimerosal--containing childhood vaccines and the prevalence of autism from the late 1980s through the mid-1990s. In contrast, there was a potential correlation between the number of primary pediatric measles-containing vaccines administered and the prevalence of autism during the 1980s. In addition, it was found that there were statistically significant odds ratios for the development of autism following increasing doses of mercury from thimerosal-containing vaccines (birth cohorts: 1985 and 1990-1995) in comparison to a baseline measurement (birth cohort: 1984). The contribution of thimerosal from childhood vaccines (>50% effect) was greater than MMR vaccine on the prevalence of autism observed in this study.
The results of this study agree with a number of previously published studies. These studies have shown that there is biological plausibility and epidemiological evidence showing a direct relationship between increasing doses of mercury from thimerosal-containing vaccines and neurodevelopmental disorders, and measles-containing vaccines and serious neurological disorders. It is recommended that thimerosal be removed from all vaccines, and additional research be undertaken to produce a MMR vaccine with an improved safety profile.
After concerns about the possible toxicity of thimerosal-containing vaccines in the United States, this study was designed to investigate whether there is a relationship between the amount of thimerosal that an infant receives via diphtheria-tetanus-whole-cell pertussis (DTP) or diphtheria-tetanus (DT) vaccination at a young age and subsequent neurodevelopmental disorders.
A retrospective cohort study was performed using 109 863 children who were born from 1988 to 1997 and were registered in general practices in the United Kingdom that contributed to a research database. The disorders investigated were general developmental disorders, language or speech delay, tics, attention-deficit disorder, autism, unspecified developmental delays, behavior problems, encopresis, and enuresis. Exposure was defined according to the number of DTP/DT doses received by 3 and 4 months of age and also the cumulative age-specific DTP/DT exposure by 6 months. Each DTP/DT dose of vaccine contains 50 microg of thimerosal (25 microg of ethyl mercury). Hazard ratios (HRs) for the disorders were calculated per dose of DTP/DT vaccine or per unit of cumulative DTP/DT exposure.
Only in 1 analysis for tics was there some evidence of a higher risk with increasing doses (Cox's HR: 1.50 per dose at 4 months; 95% confidence interval [CI]: 1.02-2.20). Statistically significant negative associations with increasing doses at 4 months were found for general developmental disorders (HR: 0.87; 95% CI: 0.81-0.93), unspecified developmental delay (HR: 0.80; 95% CI: 0.69-0.92), and attention-deficit disorder (HR: 0.79; 95% CI: 0.64-0.98). For the other disorders, there was no evidence of an association with thimerosal exposure.
With the possible exception of tics, there was no evidence that thimerosal exposure via DTP/DT vaccines causes neurodevelopmental disorders.
Although mercury has been proven to be a neurotoxicant, there is a lack of data to evaluate the causal relationship between mercury and autism. We aim to see if there is increased mercury exposure in children with autistic spectrum disorder. We performed a cross-sectional cohort study over a 5-month period in 2000 to compare the hair and blood mercury levels of children with autistic spectrum disorder (n = 82; mean age 7.2 years) and a control group of normal children (n = 55; mean age 7.8 years). There was no difference in the mean mercury levels. The mean blood mercury levels of the autistic and control groups were 19.53 and 17.68 nmol/L, respectively (P = .15), and the mean hair mercury levels of the autistic and control groups were 2.26 and 2.07 ppm, respectively (P = .79). Thus, the results from our cohort study with similar environmental mercury exposure indicate that there is no causal relationship between mercury as an environmental neurotoxin and autism.
Thimerosal is an ethylmercury-containing preservative in vaccines. Toxicokinetic studies have shown children received doses of mercury from thimerosal-containing vaccines (TCVs) that were in excess of safety guidelines. Previously, an ecological study showing a significant association between TCVs and neurodevelopmental disorders (NDs) in the US was published in this journal.
A two phased population-based epidemiological study was undertaken. Phase one evaluated reported NDs to the Vaccine Adverse Event Reporting System (VAERS) following thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis (DTaP) vaccines in comparison to thimerosal-free DTaP vaccines administered from 1997 through 2001. Phase two evaluated the automated Vaccine Safety Datalink (VSD) for cumulative exposures to mercury from TCVs at 1-, 2-, 3-, and 6-months-of-age for infants born from 1992 through 1997 and the eventual risk of developing NDs.
Phase one showed significantly increased risks for autism, speech disorders, mental retardation, personality disorders, and thinking abnormalities reported to VAERS following thimerosal-containing DTaP vaccines in comparison to thimerosal-free DTaP vaccines. Phase two showed significant associations between cumulative exposures to thimerosal and the following types of NDs: unspecified developmental delay, tics, attention deficit disorder (ADD), language delay, speech delay, and neurodevelopmental delays in general.
This study showed that exposure to mercury from TCVs administered in the US was a consistent significant risk factor for the development of NDs. It is clear from these data and other recent publications linking TCVs with NDs that additional ND research should be undertaken in the context of evaluating mercury-associated exposures and thimerosal-free vaccines should be made available.
Thimerosal is a preservative that has been used in manufacturing vaccines since the 1930s. Reports have indicated that infants can receive ethylmercury (in the form of thimerosal) at or above the U.S. Environmental Protection Agency guidelines for methylmercury exposure, depending on the exact vaccinations, schedule, and size of the infant. In this study we compared the systemic disposition and brain distribution of total and inorganic mercury in infant monkeys after thimerosal exposure with those exposed to MeHg. Monkeys were exposed to MeHg (via oral gavage) or vaccines containing thimerosal (via intramuscular injection) at birth and 1, 2, and 3 weeks of age. Total blood Hg levels were determined 2, 4, and 7 days after each exposure. Total and inorganic brain Hg levels were assessed 2, 4, 7, or 28 days after the last exposure. The initial and terminal half-life of Hg in blood after thimerosal exposure was 2.1 and 8.6 days, respectively, which are significantly shorter than the elimination half-life of Hg after MeHg exposure at 21.5 days. Brain concentrations of total Hg were significantly lower by approximately 3-fold for the thimerosal-exposed monkeys when compared with the MeHg infants, whereas the average brain-to-blood concentration ratio was slightly higher for the thimerosal-exposed monkeys (3.5 +/- 0.5 vs. 2.5 +/- 0.3). A higher percentage of the total Hg in the brain was in the form of inorganic Hg for the thimerosal-exposed monkeys (34% vs. 7%). The results indicate that MeHg is not a suitable reference for risk assessment from exposure to thimerosal-derived Hg. Knowledge of the toxicokinetics and developmental toxicity of thimerosal is needed to afford a meaningful assessment of the developmental effects of thimerosal-containing vaccines.
To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001). Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.
The objective of this study was to assess the levels of 39 toxic metals and essential minerals in hair samples of children with autism spectrum disorders and their mothers compared to controls. Inductively coupled plasma-mass spectrometry was used to analyze the elemental content of the hair of children with autism spectrum disorders (n=51), a subset of their mothers (n=29), neurotypical children (n=40), and a subset of their mothers (n=25). All participants were recruited from Arizona. Iodine levels were 45% lower in the children with autism (p=0.005). Autistic children with pica had a 38% lower level of chromium (p=0.002). Autistic children with low muscle tone had very low levels of potassium (-66%, p=0.01) and high zinc (31%, p=0.01). The mothers of young children with autism had especially low levels of lithium (56% lower, p=0.005), and the young children (ages 3-6 yr) with autism also had low lithium (-30%, p=0.04). Low iodine levels are consistent with previous reports of abnormal thyroid function, which likely affected development of speech and cognitive skills. Low lithium in the mothers likely caused low levels of lithium in the young children, which could have affected their neurological and immunological development. Further investigations of iodine, lithium, and other elements are warranted.
To explore possible associations between autism spectrum disorders (ASD) and environmental exposures, we linked the California autism surveillance system to estimated hazardous air pollutant (HAP) concentrations compiled by the U.S. Environmental Protection Agency.
Subjects included 284 children with ASD and 657 controls, born in 1994 in the San Francisco Bay area. We assigned exposure level by census tract of birth residence for 19 chemicals we identified as potential neurotoxicants, developmental toxicants, and/or endocrine disruptors from the 1996 HAPs database. Because concentrations of many of these were highly correlated, we combined the chemicals into mechanistic and structural groups, calculating summary index scores. We calculated ASD risk in the upper quartiles of these group scores or individual chemical concentrations compared with below the median, adjusting for demographic factors.
The adjusted odds ratios (AORs) were elevated by 50% in the top quartile of chlorinated solvents and heavy metals [95% confidence intervals (CIs) , 1.1-2.1], but not for aromatic solvents. Adjusting for these three groups simultaneously led to decreased risks for the solvents and increased risk for metals (AORs for metals: fourth quartile = 1.7 ; 95% CI, 1.0-3.0 ; third quartile = 1.95 ; 95% CI, 1.2-3.1) . The individual compounds that contributed most to these associations included mercury, cadmium, nickel, trichloroethylene, and vinyl chloride.
Our results suggest a potential association between autism and estimated metal concentrations, and possibly solvents, in ambient air around the birth residence, requiring confirmation and more refined exposure assessment in future studies.
This review addresses an important area of environmental and mammalian toxicology by evaluating and comparing mercury-induced effects upon the immune responses of two evolutionarily divergent yet immunologically-related species. The mechanisms of mercury toxicology and immunotoxicology are described herein, including supporting data from the following: sources of exposure; bioavailability and biodistribution; metabolism; and laboratory and field investigations. Based upon the studies presented, the relative sensitivities of fish and human immune cells to mercury exposure are compared and contrasted with regard to mercury's ability to stimulate and/or suppress host immunocompetence. In addition, results from immune assays are compared to mercury tissue burdens, as well as to toxicological threshold level estimates. Such comparisons may help to resolve gaps in our knowledge regarding sensitivity of immunological assays, standardization of immunotoxicological techniques between species, and the extent to which the vertebrate immune system possesses functional reserve and redundancy in response to xenobiotics. A review of this type begins to provide support for the potential usefulness of fish immune cells to serve as indicators for human immunotoxicology risk assessment. Analysis of the reviewed studies supports the following conclusions in both lower and higher vertebrates: a threshold for mercury-induced immunotoxicological effects is likely; multiple exposure scenarios involving high and/or chronic exposures leading to increased body burdens are linked to increased risk of immunomodulation; and highly exposed and/or susceptible subpopulations are at greater risk of toxicological impact.
In this study, we evaluated doses of mercury from thimerosal-containing childhood immunizations in compari- son to US Federal Safety Guidelines and the effects of increasing doses of mercury o n t he i ncidence o f neurodevelopment disorders and heart disease. This study showed that children received mercury from this source in excess of the Federal Safety Guidelines for the oral ingestion of methylmercury. Our analyses showed increasing r elative r isks f or neurodevelopment disorders and heart disease with increasing doses of mercury. This study provides strong epidemiological evidence for a link between mercury exposure from thimerosal-containing childhood vaccines and neurodevelopment disorders.
Background
In 1999, concerns were raised that vaccines containing the preservative Thimerosal™ might increase the risk of autism and/or other neurodevelopmental disorders.
Mercury toxicity and intoxication (poisoning) are realities that every American needs to face. Both the Environmental Protection Agency and National Academy of Science state that between 8 to 10% of American women have mercury levels that would render any child they gave birth to neurological disorders. One of six children in the USA have a neurodevelopmental disorder according to the Centers for Disease Control and Preven- tion. Yet our dentistry and medicine continue to expose all patients to mercury. This article discusses the obvious sources of mercury exposures that can be easily prevented. It also points out that genetic susceptibility and exposures to other materials that synergistically enhance mercury and ethyl- mercury toxicity need to be evaluated, and that by their existence prevent the actual determination of a "safe level" of mercury exposure for all. The mercury sources we consider are from dentistry and from drugs, mainly vaccines, that, in today's world are not only unnecessary sources, but also sources that are being increasingly recognized as being significantly deleterious to the health of many. © Copyright 2005, Pearblossom Private School, Inc.-Publishing Division.
The frequency of ear infections, ear tube drainage, and deafness was examined through parental reports in autistic and yoke-matched, normal children. For the autistic group these difficulties were additionally examined as a function of the children's cognitive and communication abilities, verbal versus nonverbal status, sex, and degree of autistic symptomatology. Autistic children had a greater incidence of ear infections than matched normal peers. Lower-functioning children had an earlier onset of ear infections than their higher-functioning autistic peers. Ear infections coexisted with low-set ears, and with a higher autistic symptomatology score. The findings are discussed in terms of greater CNS vulnerability in the autistic children, which is likely present since embryogenesis. The possible adverse consequences of intermittent hearing loss on language, cognitive, and socioaffective development are considered.
Human primary teeth have been used as indicators of heavy metal exposure for several decades, but the knowledge about the influence of factors such as tooth type and the presence of caries and roots on metal concentrations is limited. Samples of tooth powder from more than 1200 Norwegian primary teeth without fillings have been analyzed for lead, zinc and cadmium content, and 554 of them for mercury. The material represents all groups of tooth types (incisors, canines and molars), carious and non-carious teeth, and teeth with and without roots. Here we investigate how tooth group and the presence of caries and roots are related to metal concentrations in the teeth. We find that carious teeth have higher metal concentrations than non-carious teeth; the difference was statistically significant for lead, mercury and zinc. Teeth with roots have higher lead and zinc concentrations than teeth without roots. We find differences in metal concentrations between the tooth groups for lead, mercury and zinc. Significant, positive correlations are found between lead and the three other metals and between mercury and zinc. We conclude that metal concentrations in primary teeth are affected by the presence of caries and roots and by tooth group.
Most strains of staphylococci, streptococci, yeasts and E. coli isolated from human faeces, could synthesize methylmercury compounds. In contrast, few strains of obligate anaerobes could do so. Up to 6 ng methylmercury/ml were formed in 44 h from 2 mug mercuric chloride.
The frequency of ear infections, ear tube drainage, and deafness was examined through parental reports in autistic and yoke-matched, normal children. For the autistic group these difficulties were additionally examined as a function of the children's cognitive and communication abilities, verbal versus nonverbal status, sex, and degree of autistic symptomatology. Autistic children had a greater incidence of ear infections than matched normal peers. Lower-functioning children had an earlier onset of ear infections than their higher-functioning autistic peers. Ear infections coexisted with low-set ears, and with a higher autistic symptomatology score. The findings are discussed in terms of greater CNS vulnerability in the autistic children, which is likely present since embryogenesis. The possible adverse consequences of intermittent hearing loss on language, cognitive, and socioaffective development are considered.
As bile is the main route of elimination of many metals, a large number of studies have been directed toward the characterization of the hepatobiliary transport of both endogenous and exogenous metals. Although some progress has been made, we still know little of the basic mechanisms involved in the hepatocellular uptake of metals, in their intracellular translocation and metabolism, or in their transport into bile. Our recent studies have focused on the last step in the hepatobiliary transport of mercury, namely, the secretion of the metal from liver cells into bile. The rate of secretion of methyl and inorganic mercury into bile was low in suckling rats and rapidly increased to adult rates soon after weaning. These changes closely followed similar developmental changes in the biliary secretion of reduced glutathione (GSH). When GSH secretion into bile was completely inhibited, without changing hepatic levels of GSH or mercury, mercury secretion was also completely blocked. Mercury secretion paralleled individual and sex-related differences in GSH secretion. At the same time, the secretion of mercury was independent of bile flow, of the thiol and mercury concentration gradients between bile and liver cells, and of those between bile and plasma. Our results, therefore, indicate a close coupling between the secretion of mercury and that of GSH. These in vivo findings, along with in vitro studies by others in vesicles isolated from the canalicular membrane of the liver cell, indicate a carrier-mediated transport system for GSH, but the nature of the linkage of this transport system with mercury secretion is not yet fully established. Our data and those in the literature are consistent with the involvement of at least two steps in the movement of mercury from liver cells to bile--the formation of a mercury-glutathione complex in the liver cell, followed by the secretion of this complex through a process closely linked to GSH secretion. The identification of GSH as an endogenous complexing agent in the transport of metals between tissues and body fluids now permits the design of therapeutic strategies aimed at exploiting this transport vehicle to effect the removal of metals via physiological routes of excretion. The present discussion considers the role of GSH in the hepatobiliary transport of metals. In doing so, a brief review is given of current understanding of hepatic GSH metabolism and transport.
Dentine lead levels were measured from shed deciduous teeth of 761 Philadelphia schoolchildren with no prior history of lead poisoning and residing in two school districts, one considered high risk for lead exposure, and one considered low risk. Black children in public schools from areas of deteriorated housing had marked elevations of dentine lead (mean of 198 μg per gram, in 174 children), with 20 per cent of the children having levels in the range associated with toxicity. White children from newer housing had the lowest levels (mean of 41.7μg per gram, 304 children), but a group of white children from intact housing living near and attending school adjacent to a major lead processor also had elevations of dentine lead (mean of 136 μg per gram, 71 determinations). Lead exposure as defined by dentine lead levels is more serious and widespread than previously acknowledged, and extends to groups other than those traditionally accepted as at risk. (N Engl J Med 290:245–248, 1974).
Mice fed either (1) a pelleted rodent diet, (2) evaporated milk, or (3) a synthetic diet (high protein, low fat) exhibited different rates of whole body mercury elimination and fecal mercury excretion after exposure (per os) to methylmercuric chloride. The percentage of the total mercury body burden present as mercuric mercury was highest (35.3%) in mice fed the synthetic diet (which had the highest rate of mercury elimination) and lowest (6.6%) in the animals having the lowest mercury elimination rate (milk-fed mice). Mice fed the synthetic diet had lower mercury concentrations and had a higher proportion of mercuric mercury in their tissues than the mice from the other dietary groups. Treatment of the mice with antibiotics throughout the experimental period to suppress the gut flora reduced fecal mercury excretion and the dietary differences in whole body retention of mercury. Tissue mercury concentrations and proportion of organic mercury in feces, cecal contents, liver, and kidneys were increased by antibiotic treatment of mice fed the pelleted or synthetic diets. These results are consistent with the theory that demethylation of methylmercury by intestinal microflora is a major factor determining the excretion rate of mercury.
The interrelation between the biliary transport of glutathione (GSH) and of inorganic mercury was investigated in suckling and adult male and female rats. The 14-day-old rat secreted inorganic mercury into bile at one-seventh the rate of the 28-day-old rat. Development of the ability to secrete mercury paralleled development of the ability to secrete GSH. The inability of the 14-day-old rat to secrete mercury and GSH occurred despite hepatic tissue concentrations of both of these compounds which were similar to those of adult rats. In adult rats, inhibition of GSH secretion by sulfobromophthalein (BSP) administration resulted in a parallel inhibition of mercury secretion. Conversely, the increase in the rate of GSH secretion into bile after cysteine or GSH administration was accompanied by an increase in the rate of mercury secretion into bile. The changes in the biliary secretion of mercury and of GSH after treatment with cysteine or GSH were not closely parallel, probably because of the tissue redistribution of mercury effected by these sulfhydryl-containing compounds. Mercury secretion into bile was independent of the changes in bile flow produced by dehydrocholate (DHC) or hypertonic sucrose, but it was closely related to the rate of GSH secretion. Further, sex differences and individual variability in the biliary secretion of inorganic mercury were correlated with differing abilities to secrete GSH into bile. These results suggest that the biliary secretion of inorganic mercury is in large part dependent on the biliary transport of GSH.
The effect of intestinal flora on the absorption and dispositon of mercury in tissues was investigated using conventional rats, and rats treated with antibiotics to eliminate their gut flora. Antibiotic-treated rats given [203Hg]-labeled methylmercuric chloride orally had significantly more mercury in their tissues, especially in kidney, brain, lung, blood, and skeletal muscle, and also excreted less mercury in the feces than conventional rats. Furthermore, in the kidneys of the antibiotic-treated rats, the proportion of mercury present as organic mercury was greater than in the kidneys of the conventional rats. The results suppport the hypothesis that the metabolism of methylmercuric chloride by the gut flora reduces the tissue content of mercury. When rats were administered 10 mg methylmercuric chloride/kg . day for 6 days, four of five of those given antibiotics developed neurological symptoms of toxicity, whereas only one of five conventional rats given methylmercuric chloride was affected.
Seventy-nine primary (deciduous) teeth were excavated in 1978 underneath the floor of the stave church in Uvdal, Buskerud County, Norway. The mercury content of 57 teeth was measured by means of cold vapor atomic absorption spectrophotometry. As a comparison, 124 primary teeth from modern Norway were analyzed. A significant statistical difference was found between the two sets of material. In the Uvdal material a correlation was found between the mercury and copper contents. For the modern material a correlation was found between mercury and lead, and between mercury and zinc. The authors maintain that the values found for the Uvdal material represent base-line values for mercury in primary teeth, and probably reflect uptake from natural environmental sources only. Furthermore, these values may be used for reference in studies of other preindustrial, as well as modern, primary teeth. Our findings also indicate a higher level of mercury in modern than in preindustrial primary teeth in Norway.
The ubiquitous nature of mercury in the environment, its global atmospheric cycling, and its toxicity to humans at levels that are uncomfortably close to exposures experienced by a proportion of the population are some of the current concerns associated with this pollutant. The purpose of this review is to critically evaluate the scientific quality of published reports involving human exposures to mercury and associated health outcomes as an aid in the risk evaluation of this chemical. A comprehensive review of the scientific literature involving human exposures to mercury was performed and each publication evaluated using a defined set of criteria that are considered standards in epidemiologic and toxicologic research. Severe, sometimes fatal, effects of mercury exposure at high levels were primarily reported as case studies. The disasters in Minamata, Japan, in the 1950s and in Iraq in 1971-1972 clearly demonstrated neurologic effects associated with ingestion of methylmercury both in adults and in infants exposed in utero. The effects were convincingly associated with methylmercury ingestion, despite limitations of the study design. Several well-conducted studies have investigated the effects of methylmercury at levels below those in the Iraq incident but have not provided clear evidence of an effect. The lower end of the dose-response curve constructed from the Iraq data therefore still needs to be confirmed. The studies of mercury exposure in the workplace were mainly of elemental or inorganic mercury, and effects that were observed at relatively low exposure levels were primarily neurologic and renal. Several studies have investigated effects associated with dental amalgam but have been rated as inconclusive because of methodologic deficiencies. In our overall evaluation, 29 of 110 occupational studies and 20 of 54 studies where exposure occurred in the natural environment provided at least suggestive evidence of an exposure-related effect.
Autism is a syndrome characterized by impairments in social relatedness and communication, repetitive behaviors, abnormal movements, and sensory dysfunction. Recent epidemiological studies suggest that autism may affect 1 in 150 US children. Exposure to mercury can cause immune, sensory, neurological, motor, and behavioral dysfunctions similar to traits defining or associated with autism, and the similarities extend to neuroanatomy, neurotransmitters, and biochemistry. Thimerosal, a preservative added to many vaccines, has become a major source of mercury in children who, within their first two years, may have received a quantity of mercury that exceeds safety guidelines. A review of medical literature and US government data suggests that: (i) many cases of idiopathic autism are induced by early mercury exposure from thimerosal; (ii) this type of autism represents an unrecognized mercurial syndrome; and (iii) genetic and non-genetic factors establish a predisposition whereby thimerosal's adverse effects occur only in some children.
This review addresses an important area of environmental and mammalian toxicology by evaluating and comparing mercury-induced effects upon the immune responses of two evolutionarily divergent yet immunologically-related species. The mechanisms of mercury toxicology and immunotoxicology are described herein, including supporting data from the following: sources of exposure; bioavailability and biodistribution; metabolism; and laboratory and field investigations. Based upon the studies presented, the relative sensitivities of fish and human immune cells to mercury exposure are compared and contrasted with regard to mercury's ability to stimulate and/or suppress host immunocompetence. In addition, results from immune assays are compared to mercury tissue burdens, as well as to toxicological threshold level estimates. Such comparisons may help to resolve gaps in our knowledge regarding sensitivity of immunological assays, standardization of immunotoxicological techniques between species, and the extent to which the vertebrate immune system possesses functional reserve and redundancy in response to xenobiotics. A review of this type begins to provide support for the potential usefulness of fish immune cells to serve as indicators for human immunotoxicology risk assessment. Analysis of the reviewed studies supports the following conclusions in both lower and higher vertebrates: a threshold for mercury-induced immunotoxicological effects is likely; multiple exposure scenarios involving high and/or chronic exposures leading to increased body burdens are linked to increased risk of immunomodulation; and highly exposed and/or susceptible subpopulations are at greater risk of toxicological impact.
Blood organic mercury (i.e., methyl mercury) concentrations among 1,709 women who were participants in the National Health and Nutrition Examination Survey (NHANES) in 1999 and 2000 (1999-2000 NHANES) were 0.6 microg/L at the 50th percentile and ranged from concentrations that were nondetectable (5th percentile) to 6.7 microg/L (95th percentile). Blood organic/methyl mercury reflects methyl mercury intake from fish and shellfish as determined from a methyl mercury exposure parameter based on 24-hr dietary recall, 30-day food frequency, and mean concentrations of mercury in the fish/shellfish species reported as consumed (multiple correlation coefficient > 0.5). Blood organic/methyl mercury concentrations were lowest among Mexican Americans and highest among participants who designated themselves in the Other racial/ethnic category, which includes Asians, Native Americans, and Pacific Islanders. Blood organic/methyl mercury concentrations were ~1.5 times higher among women 30-49 years of age than among women 16-29 years of age. Blood mercury (BHg) concentrations were seven times higher among women who reported eating nine or more fish and/or shellfish meals within the past 30 days than among women who reported no fish and/or shellfish consumption in the past 30 days. Blood organic/methyl mercury concentrations greater than or equal to 5.8 microg/L were lowest among Mexican Americans (2.0%) and highest among examinees in the Other racial/ethnic category (21.7%). Based on the distribution of BHg concentrations among the adult female participants in 1999-2000 NHANES and the number of U.S. births in 2000, > 300,000 newborns each year in the United States may have been exposed in utero to methyl mercury concentrations higher than those considered to be without increased risk of adverse neurodevelopmental effects associated with methyl mercury exposure.