Showing papers in "Current Environmental Health Reports in 2015"

Socioeconomic Disparities and Air Pollution Exposure: a Global Review

Abstract: The existing reviews and meta-analyses addressing unequal exposure of environmental hazards on certain populations have focused on several environmental pollutants or on the siting of hazardous facilities. This review updates and contributes to the environmental inequality literature by focusing on ambient criteria air pollutants (including NOx), by evaluating studies related to inequality by socioeconomic status (as opposed to race/ethnicity) and by providing a more global perspective. Overall, most North American studies have shown that areas where low-socioeconomic-status (SES) communities dwell experience higher concentrations of criteria air pollutants, while European research has been mixed. Research from Asia, Africa, and other parts of the world has shown a general trend similar to that of North America, but research in these parts of the world is limited.

Manganese Toxicity Upon Overexposure: a Decade in Review

Abstract: Exposure to manganese (Mn) causes clinical signs and symptoms resembling, but not identical to, Parkinson's disease. Since our last review on this subject in 2004, the past decade has been a thriving period in the history of Mn research. This report provides a comprehensive review on new knowledge gained in the Mn research field. Emerging data suggest that beyond traditionally recognized occupational manganism, Mn exposures and the ensuing toxicities occur in a variety of environmental settings, nutritional sources, contaminated foods, infant formulas, and water, soil, and air with natural or man-made contaminations. Upon fast absorption into the body via oral and inhalation exposures, Mn has a relatively short half-life in blood, yet fairly long half-lives in tissues. Recent data suggest Mn accumulates substantially in bone, with a half-life of about 8-9 years expected in human bones. Mn toxicity has been associated with dopaminergic dysfunction by recent neurochemical analyses and synchrotron X-ray fluorescent imaging studies. Evidence from humans indicates that individual factors such as age, gender, ethnicity, genetics, and pre-existing medical conditions can have profound impacts on Mn toxicities. In addition to body fluid-based biomarkers, new approaches in searching biomarkers of Mn exposure include Mn levels in toenails, non-invasive measurement of Mn in bone, and functional alteration assessments. Comments and recommendations are also provided with regard to the diagnosis of Mn intoxication and clinical intervention. Finally, several hot and promising research areas in the next decade are discussed.

Microbial Contamination of Drinking Water and Human Health from Community Water Systems

Abstract: A relatively short list of reference viral, bacterial and protozoan pathogens appears adequate to assess microbial risks and inform a system-based management of drinking waters. Nonetheless, there are data gaps, e.g. human enteric viruses resulting in endemic infection levels if poorly performing disinfection and/or distribution systems are used, and the risks from fungi. Where disinfection is the only treatment and/or filtration is poor, cryptosporidiosis is the most likely enteric disease to be identified during waterborne outbreaks, but generally non-human-infectious genotypes are present in the absence of human or calf fecal contamination. Enteric bacteria may dominate risks during major fecal contamination events that are ineffectively managed. Reliance on culture-based methods exaggerates treatment efficacy and reduces our ability to identify pathogens/indicators; however, next-generation sequencing and polymerase chain reaction approaches are on the cusp of changing that. Overall, water-based Legionella and non-tuberculous mycobacteria probably dominate health burden at exposure points following the various societal uses of drinking water.

Oral Chromium Exposure and Toxicity

Abstract: Hexavalent chromium [Cr(VI)] is a known carcinogen when inhaled. However, inhalational exposure to Cr(VI) affects only a small portion of the population, mainly by occupational exposures. In contrast, oral exposure to Cr(VI) is widespread and affects many people throughout the globe. In 2008, the National Toxicology Program (NTP) released a 2-year study demonstrating that ingested Cr(VI) was carcinogenic in rats and mice. The effects of Cr(VI) oral exposure are mitigated by reduction in the gut; however, a portion evades the reductive detoxification and reaches target tissues. Once Cr(VI) enters the cell, it ultimately gets reduced to Cr(III), which mediates its toxicity via induction of oxidative stress during the reduction while Cr intermediates react with protein and DNA. Cr(III) can form adducts with DNA that may lead to mutations. This review will discuss the potential adverse effects of oral exposure to Cr(VI) by presenting up-to-date human and animal studies, examining the underlying mechanisms that mediate Cr(VI) toxicity, as well as highlighting opportunities for future research.

Perinatal and Childhood Exposure to Cadmium, Manganese, and Metal Mixtures and Effects on Cognition and Behavior: A Review of Recent Literature

Abstract: Lead (Pb) and mercury (Hg) neurotoxicity is well established. In recent years, a growing body of evidence suggests that environmental exposure to other metals including arsenic (As), cadmium (Cd), and manganese (Mn) and their mixtures also poses public health threats. In this paper, we summarize the recent literature examining the relationship of prenatal and childhood environmental metal exposures with cognitive and behavioral outcomes in children. We conducted a literature search to identify epidemiologic studies that examined the relationship of Cd, Mn, and metal mixtures with children's neurodevelopmental/cognitive and behavioral outcomes. We restricted the search to peer-reviewed studies published in English between January 2009 and March 2015. We identified a total of 31 articles of which 16, 17, and 16 studies examined the effects of Cd, Mn, or metal mixtures, respectively. Based on our review, there is suggestive evidence that prenatal/childhood Cd exposure may be associated with poorer cognition, but additional research is clearly needed. We found little evidence of behavioral effects of early life Cd exposure, and no studies found a significant relationship with attention deficit hyperactivity disorder. Studies of early life Mn exposure consistently reported negative impacts on both cognition and behavior. There is also growing evidence that co-exposure to multiple metals can result in increased neurotoxicity compared to single-metal exposure, in particular during early life. Few studies have evaluated behavioral effects related to metal co-exposure.

Overview of Disinfection By-products and Associated Health Effects.

Abstract: The presence of chemical compounds formed as disinfection by-products (DBPs) is widespread in developed countries, and virtually whole populations are exposed to these chemicals through ingestion, inhalation, or dermal absorption from drinking water and swimming pools. Epidemiological evidence has shown a consistent association between long-term exposure to trihalomethanes and the risk of bladder cancer, although the causal nature of the association is not conclusive. Evidence concerning other cancer sites is insufficient or mixed. Numerous studies have evaluated reproductive implications, including sperm quality, time to pregnancy, menstrual cycle, and pregnancy outcomes such as fetal loss, fetal growth, preterm delivery, and congenital malformation. The body of evidence suggests only minor effects from high exposure during pregnancy on fetal growth indices such as small for gestational age (SGA) at birth. Populations highly exposed to swimming pools such as pool workers and professional swimmers show a higher prevalence of respiratory symptoms and asthma, respectively, although the direction of the association, and thus causality, is not clear among professional swimmers. The risk of asthma, wheezing, eczema, and other respiratory outcomes among children attending swimming pools has been the object of extensive research. Early studies suggested a positive association, while subsequent larger studies found no correlations or showed a protective association. Future research should develop methods to evaluate the effects of the DBP mixture and the interaction with personal characteristics (e.g., genetics, lifestyle), clarify the association between swimming pools and respiratory health, evaluate the occurrence of DBPs in low- and middle-income countries, and evaluate outcomes suggested by animal studies that have not been considered in epidemiological investigations.

Green Buildings and Health

Abstract: Green building design is becoming broadly adopted, with one green building standard reporting over 3.5 billion square feet certified to date. By definition, green buildings focus on minimizing impacts to the environment through reductions in energy usage, water usage, and minimizing environmental disturbances from the building site. Also by definition, but perhaps less widely recognized, green buildings aim to improve human health through design of healthy indoor environments. The benefits related to reduced energy and water consumption are well-documented, but the potential human health benefits of green buildings are only recently being investigated. The objective of our review was to examine the state of evidence on green building design as it specifically relates to indoor environmental quality and human health. Overall, the initial scientific evidence indicates better indoor environmental quality in green buildings versus non-green buildings, with direct benefits to human health for occupants of those buildings. A limitation of much of the research to date is the reliance on indirect, lagging and subjective measures of health. To address this, we propose a framework for identifying direct, objective and leading “Health Performance Indicators” for use in future studies of buildings and health.

Drinking Water Arsenic Contamination, Skin Lesions, and Malignancies: A Systematic Review of the Global Evidence

Abstract: Skin lesions and cancer are known manifestations of chronic exposure to arsenic contaminated drinking water. Epidemiologic data primarily comes from regions with exposures 1–2 orders of magnitude above the current World Health Organization (WHO) guidelines of 10 μg/L. Emerging evidence indicates that more common exposures may also be related to both noncancerous and cancerous changes to the skin. In this review, we focus on the body of epidemiologic literature that encompasses exposures within the WHO guidelines, excluding studies that lacked individual exposure estimates and case reports. For skin lesions and skin cancers, 15 and 10 studies were identified that met our criteria, respectively. For skin lesions, a consistent dose-response relationship with water arsenic has been observed, with increased risk evident at low- to moderate-dose exposure. Of the larger studies of specific histologic types of skin cancers, although with differing exposure definitions, there was evidence of dose-related relationships with both basal cell carcinomas and squamous cell carcinomas. The effect of arsenic exposure on skin lesion risk is likely modified by genetic variants that influence arsenic metabolism. Accumulating evidence suggests that arsenic may increase risk of skin lesions and skin cancers at levels not previously considered harmful, and that genetic factors may influence risk.

The Impact of Bisphenol A and Phthalates on Allergy, Asthma, and Immune Function: a Review of Latest Findings

Abstract: In recent years, the impact of environmental exposure to chemicals and their immunological effects, including the development of allergy, has been a topic of great interest Epidemiologic studies indicate that exposure to endocrine-disrupting chemicals produced in high volumes, including bisphenol A (BPA) and phthalates, is ubiquitous The links between their exposure and the development of allergy, asthma, and immune dysfunction have been studied in vitro, in vivo, and through human cohort studies The purpose of this review is to examine the current body of research and to highlight deficits and strengths of current findings Emerging science indicates that deleterious immunologic changes, including increased propensity to develop wheeze, allergy, and asthma after dietary and inhalation exposure to these chemicals, may be occurring

Health Effects of Noise Exposure in Children

Abstract: Environmental noise exposure, such as road traffic noise and aircraft noise, is associated with a range of health outcomes in children. Children demonstrate annoyance responses to noise, and noise is also related to lower well-being and stress responses, such as increased levels of adrenaline and noradrenaline. Noise does not cause more serious mental health problems, but there is growing evidence for an association with increased hyperactivity symptoms. Studies also suggest that noise might cause changes in cardiovascular functioning, and there is some limited evidence for an effect on low birth weight. There is robust evidence for an effect of school noise exposure on children’s cognitive skills such as reading and memory, as well as on standardised academic test scores. Environmental noise does not usually reach levels that are likely to affect children’s hearing; however, increasing use of personal electronic devices may leave some children exposed to harmful levels of noise.

Air Pollution and Autism Spectrum Disorders: Causal or Confounded?

Abstract: In the last decade, several studies have examined the association between perinatal exposure to ambient air pollution and risk of autism spectrum disorder (ASD). These studies have largely been consistent, with associations seen with different aspects of air pollution, including hazardous air toxics, ozone, particulate, and traffic-related pollution. Confounding by socioeconomic status (SES) and place of residence are of particular concern, as these can be related to ASD case ascertainment and other potential causal risk factors for ASD. While all studies take steps to address this concern, residual confounding is difficult to rule out. Two recent studies of air pollution and ASD, however, present findings that strongly argue against residual confounding, especially for factors that do not vary over relatively short time intervals. These two studies, conducted in communities around the USA, found a specific association with air pollution exposure during the 3rd, but not the 1st, trimester, when both trimesters were modeled simultaneously. In this review, we discuss confounding possibilities and then explain-with the aid of directed acyclic graphs (DAGs)-why an association that is specific to a particular time window, when multiple exposure windows are simultaneously assessed, argues against residual confounding by (even unmeasured) non-time-varying factors. In addition, we discuss why examining ambient air pollution concentration as a proxy for personal exposure helps avoid confounding by personal behavior differences, and the implications of measurement error in using ambient concentrations as a proxy for personal exposures. Given the general consistency of findings across studies and the exposure-window-specific associations recently reported, the overall evidence for a causal association between air pollution and ASD is increasingly compelling.

DNA Methylation in Whole Blood: Uses and Challenges.

Abstract: Due to its convenience, the blood is commonly used in epigenomic studies, but its heterogeneous nature leads to interpretation difficulties, given the now widely recognized potential for confounding by cell composition effects. Many recent publications have reported significant associations between DNA methylation and a variety of health conditions or exposures. In this review, we summarize many of these recent publications, highlighting the findings in the context of potential cell composition effects, particularly findings that are indicative of immune response or inflammation. While there is substantial evidence for confounding by cell composition, there is nevertheless also evidence for differential DNA methylation suggestive of processes that are not cell mediated. We conclude that important biological insights still may be gained from studying DNA methylation in whole blood, either by investigating the cell composition effects themselves or processes that demonstrate associations even after adjusting for cell composition effects.

Particulate Matter from Electronic Cigarettes and Conventional Cigarettes: a Systematic Review and Observational Study

Abstract: The aim of this study is to review the literature on the composition of aerosols from electronic cigarettes (e-cigarettes) originated by human vaping and to describe the emission of particulate matter ≤2.5 μm in diameter (PM2.5) from conventional and e-cigarettes at home in real-use conditions. We conducted a systematic literature search in PubMed and Web of Science. We measured PM2.5 in four different homes: one from a conventional cigarette smoker, one from an e-cigarette user, and two from non-smokers. The review identified eight previous investigations on the composition of aerosols from e-cigarettes originated by human vaping and indicated that emissions from e-cigarettes can contain potential toxic compounds such as nicotine, carbonyls, metals, and organic volatile compounds, besides particulate matter. In the observational study, the PM2.5 median concentration was 9.88 μg/m3 in the e-cigarette user home and 9.53 and 9.36 μg/m3 in the smoke-free homes, with PM2.5 peaks concurrent with the e-cigarette puffs. Both the literature review and the observational study indicate that e-cigarettes used under real-conditions emit toxicants, including PM2.5. Further research is needed to characterize the chemicals emitted by different types of e-cigarettes and to assess secondhand exposure to e-cigarette aerosol using biological markers.

New Methods for Personal Exposure Monitoring for Airborne Particles

Abstract: Airborne particles have been associated with a range of adverse cardiopulmonary outcomes, which has driven its monitoring at stationary central sites throughout the world. Individual exposures, however, can differ substantially from concentrations measured at central sites due to spatial variability across a region and sources unique to the individual, such as cooking or cleaning in homes, traffic emissions during commutes, and widely varying sources encountered at work. Personal monitoring with small, battery-powered instruments enables the measurement of an individual’s exposure as they go about their daily activities. Personal monitoring can substantially reduce exposure misclassification and improve the power to detect relationships between particulate pollution and adverse health outcomes. By partitioning exposures to known locations and sources, it may be possible to account for variable toxicity of different sources. This review outlines recent advances in the field of personal exposure assessment for particulate pollution. Advances in battery technology have improved the feasibility of 24-h monitoring, providing the ability to more completely attribute exposures to microenvironment (e.g., work, home, commute). New metrics to evaluate the relationship between particulate matter and health are also being considered, including particle number concentration, particle composition measures, and particle oxidative load. Such metrics provide opportunities to develop more precise associations between airborne particles and health and may provide opportunities for more effective regulations.

Recreational Water and Infection: A Review of Recent Findings

Abstract: This paper reviews the latest evidence provided by epidemiological studies and quantitative microbial risk assessments (QMRAs) of infection risk from recreational water use. Studies for review were selected following a PubMed search for articles published between January 2010 and April 2014. Epidemiological studies show a generally elevated risk of gastrointestinal illness in bathers compared to non-bathers but often no clear association with water quality as measured by faecal indicator bacteria; this is especially true where study sites are impacted by non-point source pollution. Evidence from QMRAs support the lack of a consistent water quality association for non-point source-impacted beaches. It is suggested that source attribution, through quantified microbial source apportionment, linked with appropriate use of microbial source tracking methods should be employed as an integral part of future epidemiological surveys.

Environmental Susceptibility of the Sperm Epigenome During Windows of Male Germ Cell Development

Abstract: Male germ cells require multiple epigenetic reprogramming events during their lifespan to achieve reproductive capacity. An emerging body of compelling data demonstrates that environmental exposures can be embodied within the developing male germ cell as epigenetic marks. In turn, these epigenetic marks can impart information at fertilization to affect the trajectory of offspring health and development. While it is recognized that in utero epigenetic reprogramming of male germ cells is a particularly susceptible window to environmental exposures, other such windows exist during germ cell development. The objective of this review is to discuss epigenetic reprogramming events during male germ cell development and to provide supporting evidence from animal and human studies that during specific periods of development, germ cells are susceptible to environmentally induced epigenetic errors. Moving forward, the nascent field of sperm epigenetics research is likely to advance our understanding of paternal environmental determinants of offspring health and development.

Cumulative Chemical Exposures During Pregnancy and Early Development

Abstract: Industrial and consumer product chemicals are widely used, leading to ubiquitous human exposure to the most common classes Because these chemicals may affect developmental milestones, exposures in pregnant women and developing fetuses are of particular interest In this review, we discuss the prevalence of chemical exposures in pregnant women, the chemical class-specific relationships between maternal and fetal exposures, and the major sources of exposures for six chemical classes of concern: phthalates, phenols, perfluorinated compounds (PFCs), flame retardants, polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCs) Additionally, we describe the current efforts to characterize cumulative exposures to synthetic chemicals during pregnancy We conclude by highlighting gaps in the literature and discussing possible applications of the findings to reduce the prevalence of cumulative exposures during pregnancy

Household Water Treatment and Safe Storage to Prevent Diarrheal Disease in Developing Countries

Abstract: Household water treatment and safe storage (HWTS), such as boiling, filtering, or chlorinating water at home, have been shown to be effective in improving the microbiological quality of drinking water. However, estimates of their protective effect against diarrhea, a major killer, have varied widely. While results may be exaggerated because of reporting bias, this heterogeneity is consistent with other environmental interventions that are implemented with varying levels of coverage and uptake in settings where the source of exposure represents one of many transmission pathways. Evidence suggests that the effectiveness of HWTS can be optimized by ensuring that the method is microbiologically effective; (2) making it accessible to an exposed population; and (3) securing their consistent and long-term use.

Health Effects of Toxic Cyanobacteria in U.S. Drinking and Recreational Waters: Our Current Understanding and Proposed Direction.

Abstract: Cyanobacterial-derived water quality impairment issues are a growing concern worldwide. In addition to their ecological impacts, these organisms are prolific producers of bioactive secondary metabolites, many of which are known human intoxicants. To date only a handful of these compounds have been thoroughly studied and their toxicological risks estimated. While there are currently no national guidelines in place to deal with this issue, it is increasingly likely that within the next several years guidelines will be implemented. The intent of this review is to survey all relevant literature pertaining to cyanobacterial harmful algal bloom secondary metabolites, to inform a discussion on how best to manage this global public health threat.

Epigenetic Signatures as Biomarkers of Exposure.

Abstract: To advance our knowledge of the influence of environmental exposures on human health and disease, robust studies are needed. However, for many exposures, robust studies are not feasible due to limitations with current ascertainment methods and/or study designs. Epigenetics, the study of mitotically heritable, reversible information that regulates critical cell processes, has gained much attention because it offers a potential mechanism to explain how exposures can influence cell states. Therefore, most studies have focused on epigenetics as a mechanism for disease. However, emerging evidence also suggests that epigenetic marks may also serve as biomarkers of exposure. Here, we highlight findings showing that the epigenome is labile to the environment and that these exposure-associated changes show long-term stability, are specific, are detectable in accessible tissues, can predict exposure status, and can be practically implemented, thus supporting the potential for epigenetic patterns to serve as robust measures of environmental exposure.

The Pregnancy Exposome

Abstract: The exposome concept takes a holistic approach facilitated by new and emerging technologies to describe ‘the totality of human environmental (i.e. non-genetic) exposures from conception onwards, complementing the genome’. It provides a framework to advance the environmental epidemiology field that has until now focused almost exclusively on single-exposure health effects. The exposome includes an external domain, measured by methods including geo-spatial modelling, questionnaire and biomonitoring of external exposures while the internal domain is commonly assessed through molecular omics platforms. The internal domain, in part, reflects the biological response to the external domain. New statistical frameworks are required to integrate and assess exposome-health effects. The pregnancy period is a key starting point to describe the dynamic exposome, due to its heightened sensitivity and potential lifetime impact. A handful of studies have started to move towards an exposome approach in assessing the effects of the multiple exposures during pregnancy on child development. New research projects are underway to test the exposome approach on a large scale.

Industrial Food Animal Production and Community Health.

Abstract: Industrial food animal production (IFAP) is a source of environmental microbial and chemical hazards. A growing body of literature suggests that populations living near these operations and manure-applied crop fields are at elevated risk for several health outcomes. We reviewed the literature published since 2000 and identified four health outcomes consistently and positively associated with living near IFAP: respiratory outcomes, methicillin-resistant Staphylococcus aureus (MRSA), Q fever, and stress/mood. We found moderate evidence of an association of IFAP with quality of life and limited evidence of an association with cognitive impairment, Clostridium difficile, Enterococcus, birth outcomes, and hypertension. Distance-based exposure metrics were used by 17/33 studies reviewed. Future work should investigate exposure through drinking water and must improve exposure assessment with direct environmental sampling, modeling, and high-resolution DNA typing methods. Investigators should not limit study to high-profile pathogens like MRSA but include a broader range of pathogens, as well as other disease outcomes.

The Epigenetic Effects of Prenatal Cadmium Exposure

Abstract: Prenatal exposure to the highly toxic and common pollutant cadmium has been associated with adverse effects on child health and development. However, the underlying biological mechanisms of cadmium toxicity remain partially unsolved. Epigenetic disruption due to early cadmium exposure has gained attention as a plausible mode of action, since epigenetic signatures respond to environmental stimuli and the fetus undergoes drastic epigenomic rearrangements during embryogenesis. In the current review, we provide a critical examination of the literature addressing prenatal cadmium exposure and epigenetic effects in human, animal, and in vitro studies. We conducted a PubMed search and obtained eight recent studies addressing this topic, focusing almost exclusively on DNA methylation. These studies provide evidence that cadmium alters epigenetic signatures in the DNA of the placenta and of the newborns, and some studies indicated marked sexual differences for cadmium-related DNA methylation changes. Associations between early cadmium exposure and DNA methylation might reflect interference with de novo DNA methyltransferases. More studies, especially those including environmentally relevant doses, are needed to confirm the toxicoepigenomic effects of prenatal cadmium exposure and how that relates to the observed health effects of cadmium in childhood and later life.

Trends in Exposure to Chemicals in Personal Care and Consumer Products

Abstract: Synthetic organic chemicals can be used in personal care and consumer products. Data on potential human health effects of these chemicals are limited-sometimes even contradictory-but because several of these chemicals are toxic in experimental animals, alternative compounds are entering consumer markets. Nevertheless, limited information exists on consequent exposure trends to both the original chemicals and their replacements. Biomonitoring (measuring concentrations of chemicals or their metabolites in people) provides invaluable information for exposure assessment. We use phthalates and bisphenol A-known industrial chemicals-and organophosphate insecticides as case studies to show exposure trends to these chemicals and their replacements (e.g., other phthalates, non-phthalate plasticizers, various bisphenols, pyrethroid insecticides) among the US general population. We compare US trends to national trends from Canada and Germany. Exposure to the original compounds is still prevalent among these general populations, but exposures to alternative chemicals may be increasing.

Human Infections with Staphylococcus aureus CC398

Abstract: Staphylococcus aureus isolates belonging to clonal cluster 398 (CC398) have emerged over the previous decade as a risk to livestock workers. Though most of the research to date has focused on colonization with these strains, a number of infections have also been documented, ranging from mild skin infections to more serious invasive infections and even death. Here, we review existing reports of human infections with CC398 and discuss their geographic distribution, general characteristics, and implications for future research. We identified 74 publications describing CC398 infections in humans in 19 different countries, suggesting this is an emerging worldwide issue.

Hydrocarbon Release During Fuel Storage and Transfer at Gas Stations: Environmental and Health Effects.

Abstract: At gas stations, fuel is stored and transferred between tanker trucks, storage tanks, and vehicle tanks. During both storage and transfer, a small fraction of unburned fuel is typically released to the environment unless pollution prevention technology is used. While the fraction may be small, the cumulative release can be substantial because of the large quantities of fuel sold. The cumulative release of unburned fuel is a public health concern because gas stations are widely distributed in residential areas and because fuel contains toxic and carcinogenic chemicals. We review the pathways through which gasoline is chronically released to atmospheric, aqueous, and subsurface environments, and how these releases may adversely affect human health. Adoption of suitable pollution prevention technology should not only be based on equipment and maintenance cost but also on energy- and health care-saving benefits.

Arsenic Exposure and Epigenetic Alterations: Recent Findings Based on the Illumina 450K DNA Methylation Array

Abstract: Arsenic is a major public health concern worldwide. While it is an established carcinogen and associated with a number of other adverse health outcomes, the molecular mechanisms underlying arsenic toxicity are not completely clarified. There is mounting evidence from human studies suggesting that arsenic exposure is associated with epigenetic alterations, including DNA methylation. In this review, we summarize several recent human studies that have evaluated arsenic exposure using the Illumina HumanMethylation 450K BeadChip, which interrogates more than 485,000 methylation sites across the genome. Many of these studies have observed novel regions of the genome associated with arsenic exposure. However, few studies have evaluated the biological and functional relevance of these DNA methylation changes, which are still needed. We emphasize the need for future studies to replicate the identified DNA methylation signals as well as assess whether these markers are associated with risk of arsenic-related diseases.

Maternal Exposure to Synthetic Chemicals and Obesity in the Offspring: Recent Findings.

Abstract: Experimental studies suggest perinatal exposures to synthetic chemicals may be associated with early onset obesity, although this hypothesis has not been extensively examined in humans. This article summarizes the evidence relating maternal perinatal exposure to common persistent organic compounds (polychlorinated biphenyl, dichlorodiphenyldichloroethylene, dichlorodiphenyltrichloroethane, hexachlorobenzene, hexachlorocyclohexane), perfluoroalkyls, perfluorooctane sulfonate, polybrominated diphenyl ethers and tributyltin, and nonpersistent compounds (phthalates, bisphenol A) on child obesity during sensitive developmental periods. Twenty-two epidemiologic studies published from 2011 to 2015 offer inconsistent support for the obesogenic effects of most substances and are limited by relatively small sample sizes and indirect measures of adiposity. The clearest findings suggest an influence of maternal dichlorodiphenyldichloroethylene exposure on offspring overweight and obesity. Recommendations for future epidemiological research include longer follow-up of effects of pre- and postnatal exposures in large samples; utilization of direct measures of adiposity; and consideration of effect modification by sex, birth weight, dietary fat, and maternal weight status.

Effect of Gene-Mercury Interactions on Mercury Toxicokinetics and Neurotoxicity.

Abstract: Individuals differ in susceptibility to mercury neurotoxicity, in part, due to underlying genetic differences. This review aims to evaluate the state-of-the-art of the effect of (1) genetics on mercury toxicokinetics and (2) gene-mercury interactions on neurodevelopment and neurotoxicity. We conducted a PubMed search in September 2014 and retrieved 14 studies on the influence of genetics on mercury toxicokinetics and ten on neurological effects of gene-mercury interactions. Genes frequently studied for their influence on mercury toxicokinetics were mainly related to the metabolism of glutathione, but the results were contradictory for most of the genes. The gene-mercury interactions on child neurodevelopment and adult neurotoxicity reported were too few to draw any definite conclusion. So far, candidate gene approaches have not identified any major gene/s modifying the kinetics or toxicity of mercury, suggesting that these might be polygenic traits. More research is highly warranted to clarify if there are vulnerable subgroups to mercury neurotoxicity in humans.

Select Prenatal Environmental Exposures and Subsequent Alterations of Gene-Specific and Repetitive Element DNA Methylation in Fetal Tissues

Abstract: Strong evidence implicates maternal environmental exposures in contributing to adverse outcomes during pregnancy and later in life through the developmental origins of health and disease hypothesis. Recent research suggests these effects are mediated through the improper regulation of DNA methylation in offspring tissues, specifically placental tissue, which plays a critical role in fetal development. This article reviews the relevant literature relating DNA methylation in multiple tissues at or near delivery to several prenatal environmental toxicants and stressors, including cigarette smoke, endocrine disruptors, heavy metals, as well as maternal diet. These human studies expand upon previously reported outcomes in animal model interventions and include effects on both imprinted and non-imprinted genes. We have also noted some of the strengths and limitations in the approaches used, and consider the appropriate interpretation of these findings in terms of their effect size and their relationship to differential gene expression and potential health outcomes. The studies suggest an important role of DNA methylation in mediating the effects of the intrauterine environment on children’s health and a need for additional research to better clarify the role of this epigenetic mechanism as well as others.