William A. Suk

The Broad Scope of Health Effects from Chronic Arsenic Exposure: Update on a Worldwide Public Health Problem

Background: Concerns for arsenic exposure are not limited to toxic waste sites and massive poisoning events. Chronic exposure continues to be a major public health problem worldwide, affecting hundreds of millions of persons. Objectives: We reviewed recent information on worldwide concerns for arsenic exposures and public health to heighten awareness of the current scope of arsenic exposure and health outcomes and the importance of reducing exposure, particularly during pregnancy and early life. Methods: We synthesized the large body of current research pertaining to arsenic exposure and health outcomes with an emphasis on recent publications. Discussion: Locations of high arsenic exposure via drinking water span from Bangladesh, Chile, and Taiwan to the United States. The U.S. Environmental Protection Agency maximum contaminant level (MCL) in drinking water is 10 µg/L; however, concentrations of > 3,000 µg/L have been found in wells in the United States. In addition, exposure through diet is of growing concern. Knowledge of the scope of arsenic-associated health effects has broadened; arsenic leaves essentially no bodily system untouched. Arsenic is a known carcinogen associated with skin, lung, bladder, kidney, and liver cancer. Dermatological, developmental, neurological, respiratory, cardiovascular, immunological, and endocrine effects are also evident. Most remarkably, early-life exposure may be related to increased risks for several types of cancer and other diseases during adulthood. Conclusions: These data call for heightened awareness of arsenic-related pathologies in broader contexts than previously perceived. Testing foods and drinking water for arsenic, including individual private wells, should be a top priority to reduce exposure, particularly for pregnant women and children, given the potential for life-long effects of developmental exposure.

The Lancet Commission on pollution and health

Philip J Landrigan, Richard Fuller, Nereus J R Acosta, Olusoji Adeyi, Robert Arnold, Niladri (Nil) Basu, Abdoulaye Bibi Baldé, Roberto Bertollini, Stephan Bose-O’Reilly, Jo Ivey Boufford, Patrick N Breysse, Thomas Chiles, Chulabhorn Mahidol, Awa M Coll-Seck, Maureen L Cropper, Julius Fobil, Valentin Fuster, Michael Greenstone, Andy Haines, David Hanrahan, David Hunter, Mukesh Khare, Alan Krupnick, Bruce Lanphear, Bindu Lohani, Keith Martin, Karen V Mathiasen, Maureen A McTeer, Christopher J L Murray, Johanita D Ndahimananjara, Frederica Perera, Janez Potočnik, Alexander S Preker, Jairam Ramesh, Johan Rockström, Carlos Salinas, Leona D Samson, Karti Sandilya, Peter D Sly, Kirk R Smith, Achim Steiner, Richard B Stewart, William A Suk, Onno C P van Schayck, Gautam N Yadama, Kandeh Yumkella, Ma Zhong

Personalized exposure assessment : Promising approaches for human environmental health research

New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc Committee on Environmental Exposure Technology Development was convened to identify new technologies and methods for deriving personalized exposure measurements for application to environmental health studies. The committee identified a “toolbox” of methods for measuring external (environmental) and internal (biologic) exposure and assessing human behaviors that influence the likelihood of exposure to environmental agents. The methods use environmental sensors, geographic information systems, biologic sensors, toxicogenomics, and body burden (biologic) measurements. We discuss each of the methods in relation to current use in human health research; specific gaps in the development, validation, and application of the methods are highlighted. We also present a conceptual framework for moving these technologies into use and acceptance by the scientific community. The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure–disease relationships and the interaction of genetic and environmental factors in disease occurrence. Improved methods for exposure assessment will result in better means of monitoring and targeting intervention and prevention programs.

Developmental Origins of Health and Disease: Integrating Environmental Influences

There are now robust data supporting the Developmental Origins of Health and Disease (DOHaD) paradigm. This includes human and animal data focusing on nutrition or environmental chemicals during development. However, the term DOHaD has not been generally accepted as the official term to be used when one is concerned with understanding the pathophysiological basis for how environmental influences acting during early development influence the risk of later noncommunicable diseases. Similarly, there is no global research or public health program built around the DOHaD paradigm that encompasses all aspects of environment. To better inform the global health efforts aimed at addressing the growing epidemic of chronic noncommunicable diseases of environmental origin, we propose a two-pronged approach: first, to make it clear that the current concept of DOHaD comprehensively includes a range of environmental factors and their relevance to disease occurrence not just throughout the life span but potentially across several generations; and second, to initiate the discussion of how adoption of DOHaD can promote a more realistic, accurate, and integrative approach to understanding environmental disruption of developmental programming and better inform clinical and policy interventions.

Developmental Origins of Health and Disease

There are now robust data supporting the Developmental Origins of Health and Disease (DOHaD) paradigm. This includes human and animal data focusing on nutrition or environmental chemicals during development. However, the term DOHaD has not been generally accepted as the official term to be used when one is concerned with understanding the pathophysiological basis for how environmental influences acting during early development influence the risk of later noncommunicable diseases. Similarly, there is no global research or public health program built around the DOHaD paradigm that encompasses all aspects of environment. To better inform the global health efforts aimed at addressing the growing epidemic of chronic noncommunicable diseases of environmental origin, we propose a two-pronged approach: first, to make it clear that the current concept of DOHaD comprehensively includes a range of environmental factors and their relevance to disease occurrence not just throughout the life span but potentially across several generations; and second, to initiate the discussion of how adoption of DOHaD can promote a more realistic, accurate, and integrative approach to understanding environmental disruption of developmental programming and better inform clinical and policy interventions.

Effects of arsenic exposure on DNA methylation in cord blood samples from newborn babies and in a human lymphoblast cell line

BackgroundAccumulating evidence indicates that in utero exposure to arsenic is associated with congenital defects and long-term disease consequences including cancers. Recent studies suggest that arsenic carcinogenesis results from epigenetic changes, particularly in DNA methylation. This study aimed to investigate DNA methylation changes as a result of arsenic exposure in utero and in vitro.MethodsFor the exposure in utero study, a total of seventy-one newborns (fifty-five arsenic-exposed and sixteen unexposed newborns) were recruited. Arsenic concentrations in the drinking water were measured, and exposure in newborns was assessed by measurement of arsenic concentrations in cord blood, nails and hair by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). In the in vitro study, human lymphoblasts were treated with arsenite at 0-100 μM for two, four and eight hours (short-term) and at 0, 0.5 and 1.0 μM for eight-weeks period (long-term). DNA methylation was analyzed in cord blood lymphocytes and lymphoblasts treated with arsenite in vitro. Global DNA methylation was determined as LINE-1 methylation using combined bisulfite restriction analysis ( COBRA) and total 5-methyldeoxycytidine (5MedC) content which was determined by HPLC-MS/MS. Methylation of p53 was determined at the promoter region using methylation-specific restriction endonuclease digestion with MspI and HpaII.ResultsResults showed that arsenic-exposed newborns had significantly higher levels of arsenic in cord blood, fingernails, toenails and hair than those of the unexposed subjects and a slight increase in promoter methylation of p53 in cord blood lymphocytes which significantly correlated with arsenic accumulation in nails (p < 0.05) was observed, while LINE-1 methylation was unchanged. Short-term in vitro arsenite treatment in lymphoblastoid cells clearly demonstrated a significant global hypomethylation, determined as reduction in LINE-1 methylation and total 5-MedC content, and p53 hypermethylation (p < 0.05). However, a slight LINE-1 hypomethylation and transient p53 promoter hypermethylation were observed following long-term in vitro treatment.ConclusionsThis study provides an important finding that in utero arsenic exposure affects DNA methylation, particularly at the p53 promoter region, which may be linked to the mechanism of arsenic carcinogenesis and the observed increased incidence of cancer later in life.

E-Waste and Harm to Vulnerable Populations: A Growing Global Problem.

Background: Electronic waste (e-waste) is produced in staggering quantities, estimated globally to be 41.8 million tonnes in 2014. Informal e-waste recycling is a source of much-needed income in many low- to middle-income countries. However, its handling and disposal in underdeveloped countries is often unsafe and leads to contaminated environments. Rudimentary and uncontrolled processing methods often result in substantial harmful chemical exposures among vulnerable populations, including women and children. E-waste hazards have not yet received the attention they deserve in research and public health agendas. Objectives: We provide an overview of the scale and health risks. We review international efforts concerned with environmental hazards, especially affecting children, as a preface to presenting next steps in addressing health issues stemming from the global e-waste problem. Discussion: The e-waste problem has been building for decades. Increased observation of adverse health effects from e-waste sites calls for protecting human health and the environment from e-waste contamination. Even if e-waste exposure intervention and prevention efforts are implemented, legacy contamination will remain, necessitating increased awareness of e-waste as a major environmental health threat. Conclusion: Global, national, and local levels efforts must aim to create safe recycling operations that consider broad security issues for people who rely on e-waste processing for survival. Paramount to these efforts is reducing pregnant women and children’s e-waste exposures to mitigate harmful health effects. With human environmental health in mind, novel dismantling methods and remediation technologies and intervention practices are needed to protect communities. Citation: Heacock M, Kelly CB, Asante KA, Birnbaum LS, Bergman AL, Bruné MN, Buka I, Carpenter DO, Chen A, Huo X, Kamel M, Landrigan PJ, Magalini F, Diaz-Barriga F, Neira M, Omar M, Pascale A, Ruchirawat M, Sly L, Sly PD, Van den Berg M, Suk WA. 2016. E-waste and harm to vulnerable populations: a growing global problem. Environ Health Perspect 124:550–555; http://dx.doi.org/10.1289/ehp.1509699

Arsenic and Environmental Health: State of the Science and Future Research Opportunities

Background: Exposure to inorganic and organic arsenic compounds is a major public health problem that affects hundreds of millions of people worldwide. Exposure to arsenic is associated with cancer and noncancer effects in nearly every organ in the body, and evidence is mounting for health effects at lower levels of arsenic exposure than previously thought. Building from a tremendous knowledge base with > 1,000 scientific papers published annually with “arsenic” in the title, the question becomes, what questions would best drive future research directions? Objectives: The objective is to discuss emerging issues in arsenic research and identify data gaps across disciplines. Methods: The National Institutes of Health’s National Institute of Environmental Health Sciences Superfund Research Program convened a workshop to identify emerging issues and research needs to address the multi-faceted challenges related to arsenic and environmental health. This review summarizes information captured during the workshop. Discussion: More information about aggregate exposure to arsenic is needed, including the amount and forms of arsenic found in foods. New strategies for mitigating arsenic exposures and related health effects range from engineered filtering systems to phytogenetics and nutritional interventions. Furthermore, integration of omics data with mechanistic and epidemiological data is a key step toward the goal of linking biomarkers of exposure and susceptibility to disease mechanisms and outcomes. Conclusions: Promising research strategies and technologies for arsenic exposure and adverse health effect mitigation are being pursued, and future research is moving toward deeper collaborations and integration of information across disciplines to address data gaps. Citation: Carlin DJ, Naujokas MF, Bradham KD, Cowden J, Heacock M, Henry HF, Lee JS, Thomas DJ, Thompson C, Tokar EJ, Waalkes MP, Birnbaum LS, Suk WA. 2016. Arsenic and environmental health: state of the science and future research opportunities. Environ Health Perspect 124:890–899; http://dx.doi.org/10.1289/ehp.1510209

Using Nutrition for Intervention and Prevention Against Environmental Chemical Toxicity and Associated Diseases

Background Nutrition and lifestyle are well-defined modulators of chronic diseases. Poor dietary habits (such as high intake of processed foods rich in fat and low intake of fruits and vegetables), as well as a sedentary lifestyle clearly contribute to today’s compromised quality of life in the United States. It is becoming increasingly clear that nutrition can modulate the toxicity of environmental pollutants. Objectives Our goal in this commentary is to discuss the recommendation that nutrition should be considered a necessary variable in the study of human disease associated with exposure to environmental pollutants. Discussion Certain diets can contribute to compromised health by being a source of exposure to environmental toxic pollutants. Many of these pollutants are fat soluble, and thus fatty foods often contain higher levels of persistent organics than does vegetable matter. Nutrition can dictate the lipid milieu, oxidative stress, and antioxidant status within cells. The modulation of these parameters by an individual’s nutritional status may have profound affects on biological processes, and in turn influence the effects of environmental pollutants to cause disease or dysfunction. For example, potential adverse health effects associated with exposure to polychlorinated biphenyls may increase as a result of ingestion of certain dietary fats, whereas ingestion of fruits and vegetables, rich in antioxidant and anti-inflammatory nutrients or bioactive compounds, may provide protection. Conclusions We recommend that future directions in environmental health research explore this nutritional paradigm that incorporates a consideration of the relationships between nutrition and lifestyle, exposure to environmental toxicants, and disease. Nutritional interventions may provide the most sensible means to develop primary prevention strategies of diseases associated with many environmental toxic insults.

Children's health in Latin America: the influence of environmental exposures

Background Chronic diseases are increasing among children in Latin America. Objective and Methods To examine environmental risk factors for chronic disease in Latin American children and to develop a strategic initiative for control of these exposures, the World Health Organization (WHO) including the Pan American Health Organization (PAHO), the Collegium Ramazzini, and Latin American scientists reviewed regional and relevant global data. Results Industrial development and urbanization are proceeding rapidly in Latin America, and environmental pollution has become widespread. Environmental threats to children’s health include traditional hazards such as indoor air pollution and drinking-water contamination; the newer hazards of urban air pollution; toxic chemicals such as lead, asbestos, mercury, arsenic, and pesticides; hazardous and electronic waste; and climate change. The mix of traditional and modern hazards varies greatly across and within countries reflecting industrialization, urbanization, and socioeconomic forces. Conclusions To control environmental threats to children’s health in Latin America, WHO, including PAHO, will focus on the most highly prevalent and serious hazards—indoor and outdoor air pollution, water pollution, and toxic chemicals. Strategies for controlling these hazards include developing tracking data on regional trends in children’s environmental health (CEH), building a network of Collaborating Centres, promoting biomedical research in CEH, building regional capacity, supporting development of evidence-based prevention policies, studying the economic costs of chronic diseases in children, and developing platforms for dialogue with relevant stakeholders. Citation Laborde A, Tomasina F, Bianchi F, Bruné MN, Buka I, Comba P, Corra L, Cori L, Duffert CM, Harari R, Iavarone I, McDiarmid MA, Gray KA, Sly PD, Soares A, Suk WA, Landrigan PJ. 2015. Children’s health in Latin America: the influence of environmental exposures. Environ Health Perspect 123:201–209; http://dx.doi.org/10.1289/ehp.1408292