Table of Contents
Title page
Copyright page
Contributors
CHAPTER 1: Introduction: Why Should We Care about Organic Chemicals and Human Health?
CHAPTER 2: Sources of Human Exposure
Introduction
Human Exposure Pathways
Chemicals of Concern
Conclusions and Recommendations
CHAPTER 3: The Burden of Cancer from Organic Chemicals
Introduction
The Global Burden of Cancer
Exposure to Organic Chemicals: Contributions to the Global Burden of Cancer
Linking Chemicals to Specific Cancer Sites
Examples of Individual Organic Chemicals
Estimating the Percentage of Cancers Attributable to Occupational and Environmental Exposures: Methodological and Conceptual Difficulties
Conclusion: Opportunities for Prevention
CHAPTER 4: Carcinogenicity and Mechanisms of Persistent Organic Pollutants
Introduction
Many POPs Are Complete Carcinogens in Animal Studies
Aspects of Cancer Induction
Cancer-Initiating Activity of POPs
Tumor-Promoting Activities of Environmental Pollutants
Progression in Carcinogenesis
Summary and Conclusion
Acknowledgments
CHAPTER 5: Diabetes and the Metabolic Syndrome
Introduction
Why Is There an Epidemic of T2D?
Human Evidence Linking POPs and T2D
Earlier Evidence
Recent Evidence: Cross-Sectional Studies
Recent Evidence: Prospective Studies
Human Evidence Linking POPs and Metabolic Syndrome
Mismatch of Time Trend: Issues Related to Inverted U-Shaped Associations
Polybrominated Biphenyl Ethers (PBDEs) and T2D
Thrifty Gene Hypothesis and POPs
POPs and Glycemic Control among Diabetic Patients
Dietary Interventions in T2D
Summary
CHAPTER 6: Mechanistic Basis for Elevation in Risk of Diabetes Caused by Persistent Organic Pollutants
Introduction
Diabetes
POPs: Novel Diabetogenic Factors
POPs and Diabetes: Mechanistic Basis
AhR
CAR and SXR
Challenges and Perspectives
CHAPTER 7: Cardiovascular Disease and Hypertension
Introduction
Animal Studies and Laboratory Evidence
Standardized Mortality Ratios (SMRs) for Heart Disease
Internal Comparisons
Summary
Discussion
Conclusions
Hypertension and Exposure to PCBs
Acknowledgment
CHAPTER 8: Obesity
Introduction
Why Such an Endocrine Hypothesis?
Which Chemicals Might Play a Role?
Epidemiological Data
Mechanisms Linking Endocrine Disruptors with Obesity
Discussion
Conclusion
CHAPTER 9: Effects and Predicted Consequences of Persistent and Bioactive Organic Pollutants on Thyroid Function
Introduction
Regulation of the TH Levels
Regulation of TH Action
Role of TH in Brain Development
Conclusions
Discussion and Conclusion
CHAPTER 10: An Overview of the Effects of Organic Compounds on Women's Reproductive Health and Birth Outcomes
Introduction
Background
Survey of Selected BOC and POC Studies
Discussion and Implications
Acknowledgments
CHAPTER 11: Effects of Organic Chemicals on the Male Reproductive System
Has Male Reproductive Health Been Impaired over Time?
Overview of the Male Reproductive System
Testicular Dysgenesis Syndrome (TDS)
Environmental Pollutants and the Male Reproductive System
Conclusions So Far and What's Next
CHAPTER 12: Effects of Endocrine-Disrupting Substances on Bone and Joint
Introduction
The Development of Bones and Joints
Physiology of Bones and Joints
Endocrine Effects on Bones and Joints
Nutrition Effects on Bones and Joints
Pathophysiology and Toxicology of EDCs on Bones and Joints
Conclusion
CHAPTER 13: Organic Chemicals and the Immune System
Introduction
Effects of Developmental Stage on Response to Organic Pollutants
Organic Chemical Exposures and Immunosuppression
Immunosuppression Mediated via Activation of the Aryl Hydrocarbon Receptor (AhR)
Pesticides other than the Organochlorines and the Immune System
Humoral Immunity and Organic Chemicals
Organics That Promote Allergy
Organics and Autoimmune Disease
Effects of Endocrine-Disruptive Chemicals on Immune System Function
Effects of Organic Chemicals on Immune System Function and Cancer
Mechanisms whereby Organic Chemicals Alter Immune System Function
Conclusion
CHAPTER 14: Exposures to Organic Pollutants and Respiratory Illnesses in Adults and Children
Introduction
Volatile Organic Compounds
Formaldehyde
Pesticides
Polynuclear Aromatic Hydrocarbons (PAHs)
Fragranced Consumer Products
Practical Solutions for Reducing Organic Pollutants Indoors
CHAPTER 15: Cognitive Function
Introduction
Polybrominated Diphenyl Ethers (PBDEs)
PAHs and Benzene
Phthalates
Bisphenol A (BPA)
Final Comments
CHAPTER 16: Intellectual Developmental Disability Syndromes and Organic Chemicals
Introduction
Fetal Alcohol Spectrum Disorder (FASD)
Attention Deficit/Hyperactivity Syndrome (ADHD)
ADHD, Neurodevelopmental Abnormalities, and Organic Contaminants
Do Organic Contaminants Cause ADHD-Like Symptoms in Adult?
Do Chemicals That Result in Reduced IQ Also Always Cause Other ADHD Symptoms?
ASDs
Conclusions
CHAPTER 17: Mechanisms of the Neurotoxic Actions of Organic Chemicals
Introduction
Organic Substances That Alter Neuronal Voltage-Activated Ion Channels
Organic Substances That Alter Transmitter Receptors and Associated Ionotropic Channels
Organics and Metabotropic Transmitter and Neurohormone Receptors
Organics That Act at Neurotransmitter Synthesis and/or Uptake
Organics That Act by Altering Neurotransmitter Metabolism
Cytotoxic Actions of Organic Chemicals
Organics That Alter Gene Expression
Organics That Alter Neuronal Migration and Structure
Studies of Organics on the Cellular Basis of Learning and Memory
Conclusions
CHAPTER 18: Parkinson's Disease
Introduction
The Genetic Hypothesis
The Environmental Hypothesis
Disease Mechanisms
PD Epidemiology
Descriptive Epidemiology: Potential Etiologic Clues
Analytic Epidemiology: Assessing Environmental Risk Factors for PD
Environmental Toxicant Associations with PD
Solvents
Polychlorinated biphenyls (PCBs)
Metals
PD Associations with Other Compounds
Summary
CHAPTER 19: Psychiatric Effects of Organic Chemical Exposure
Introduction
Psychiatric Effects of Exposures Beginning in Childhood and Adulthood
Psychiatric Issues in Prenatal Chemical Exposures
Conclusion
CHAPTER 20: Growth and Development
Introduction
Auxology
Inexactly Characterized Exposures
Conclusion
CHAPTER 21: How Much Human Disease Is Caused by Exposure to Organic Chemicals?
Introduction
The Importance of Gene–Environment Interactions
Barriers in Quantitating the Burden of Disease from Organic Chemicals
Index
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Library of Congress Cataloging-in-Publication Data:
Carpenter, David O.
Effects of persistent and bioactive organic pollutants on human health / David O. Carpenter, University at Albany, Institute for Health and the Environment.
pages cm
Includes index.
ISNB 978-1-118-15926-2 (cloth)
1. Bioactive compounds–Toxicology. 2. Organic compounds–Toxicology. 3. Persistent pollutants–Health aspects. I. Title.
RA1235.C37 2013
615.9'5–dc23
2013004573
Contributors
James S. Brown, Jr., MD, MPH, MS, Department of Psychiatry, Virginia Commonwealth University School of Medicine, Midlothian, VA
Kristopher K. Burnitz, MA, Department of Anthropology, University at Albany, Albany, NY
David O. Carpenter, MD, Institute for Health and the Environment, University at Albany, Rensselaer, NY
Mariano E. Cebrián, MSc, MD, PhD, Department of Toxicology, Center for Research and Advanced Studies (Cinvestav-IPN), Instituto Politécnico Nacional, Mexico D.F., Mexico
Chi-Hsien Chen, Department of Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Graduate Institute of Occupational Medicine and Industrial Hygiene, NTU College of Public Health, Taipei, Taiwan
Richard W. Clapp, DSc, MPH, Lowell Center for Sustainable Production, University of Massachusetts Lowell, Lowell, MA
Adrian Covaci, PhD, Toxicology Centre, University of Antwerp, Belgium
Eveline Dirinck, MD, Departments of Endocrinology, Diabetology and Metabolic Disease, Antwerp University Hospital and University of Antwerp, Belgium
José L. Domingo, PhD, Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Reus, Catalonia, Spain
Nina Dutton, MPH, Oak Ridge Institute for Science and Education (ORISE) Research Participation Program Fellow, ATSDR/CDC, Atlanta, GA
Mia V. Gallo, PhD, Department of Anthropology, University at Albany, Center for the Elimination of Minority Health Disparities, Albany, NY
Stefanie Giera, PhD, Molecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA
Howard P. Glauert, PhD, Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY
Samuel M. Goldman, MD, MPH, The Parkinson's Institute, Sunnyvale, CA
Janelle Graham, MPH, School of Public Health, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia
Yueliang Leon Guo, Department of Environmental and Occupational Medicine, National Taiwan University (NTU) College of Medicine and NTU Hospital, Graduate Institute of Occupational Medicine and Industrial Hygiene, NTU College of Public Health, Taipei, Taiwan
David R. Jacobs, Jr., PhD, Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN
Molly M. Jacobs, MPH, Lowell Center for Sustainable Production, University of Massachusetts Lowell, Lowell, MA
Duk-Hee Lee, MD, PhD, Department of Preventive Medicine, School of Medicine, Kyungpook National University, Jung-gu, Daegu, Korea
Lizbeth López-Carrillo, MSc, Dr. Ph, Center of Population Health Research, National Institute of Public Health, Col. Santa María Ahuacatitlán, Cuernavaca, Morelos, Mexico
Gabriele Ludewig, PhD, Department of Occupational and Environmental Health, Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA
Rachel I. Massey, Toxics Use Reduction Institute at UMass Lowell, Wannalancit Mills, Lowell, MA
Juliana W. Meadows, PhD, National Institute for Occupational Safety and Health, Division of Applied Science and Technology, Biomonitoring and Health Assessment Branch, Cincinnati, OH
Martí Nadal, PhD, Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Universitat Rovira i Virgili, Reus, Catalonia, Spain
Marian Pavuk, CDC Atlanta, ATSDR/CDC, Atlanta, GA
Susan R. Reutman, PhD, National Institute for Occupational Safety and Health, Cincinnati, OH
Anna Rignell-Hydbom, Division of Occupational and Environmental Medicine, Lund University, Sweden
Larry W. Robertson, PhD, MPH, ATS, Department of Occupational and Environmental Health, Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA
Krassi Rumchev, PhD, MSc, School of Public Health, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia
Jérôme Ruzzin, Department of Biology, University of Bergen, Bergen, Norway
Lars Rylander, Division of Occupational and Environmental Medicine, Lund University, Sweden
Lawrence M. Schell, PhD, Department of Anthropology, University at Albany; Department of Epidemiology and Biostatistics, School of Public Health, Center for the Elimination of Minority Health Disparities, Albany, NY
Jeff Spickett, PhD, School of Public Health, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia
Luc Van Gaal, MD, PhD, Department of Endocrinology, Diabetology and Metabolic Disease, Antwerp University Hospital and University of Antwerp, Belgium
Stijn Verhulst, MD, PhD, Department of Pediatrics, Antwerp University Hospital and University of Antwerp, Belgium
R. Thomas Zoeller, PhD, Department of Biology, Molecular and Cellular Biology Program, University of Massachusetts Amherst, Amherst, MA
CHAPTER 1
Introduction: Why Should We Care about Organic Chemicals and Human Health?
Background: The last several decades have seen an enormous increase in the development and manufacture of different organic chemicals that have proven useful for many aspects of contemporary life. The question is the degree to which some of these chemicals cause harm to human beings.
Objective: This book is directed at the goal of identifying organic chemicals that, while useful in many regards, pose risks to human health because of their biological activity and often their persistence.
Discussion: The various chapters in this book are directed at the effects of organic chemicals on the various organ systems.
Conclusions: While recognizing the wonderful benefits that have come from the development and use of many organic chemicals, serious adverse human health effects have occurred because of inadequate testing prior to use and ineffective steps to prevent release of the chemicals into air, food, water, and the environment, resulting in exposure and disease in humans. It is urgent that more effective ways be found to ensure the safety of organic chemicals, no matter how useful they may be, before they are produced and released into the environment.
Organic chemicals are a major part of everyday life in the modern world. Without question, chemicals have made our lives much easier. But at the same time, it is important to recognize that there have been some downsides to the chemical revolution. This book is focused on the downsides, but that is not to indicate that the benefits of chemicals are ignored. The use of chemicals has resulted in increased food production and safety of food, safer drinking water, improvements in life expectancy from development of pharmaceuticals and antibiotics, and greater convenience to everyone.
It is quite remarkable how much has changed in our daily lives after the development of synthetic chemicals. In the past, our carpets, draperies, and clothes were all made from natural fibers such as wool, linen, or cotton. Today, many are made from synthetic products all derived from petroleum. Most carpets, draperies, and many clothes are treated with organic flame retardants. In the past, our cookware was made of glass, pottery, and various metals. Today, we store foods in plastic, and our cookware is lined with perfluorinated compounds to prevent food from sticking. We drive in cars that may have a metal motor and frame and have glass windows, but everything else is made from plastic and petroleum products. We spray our homes with pesticides and air fresheners. We bathe our bodies with personal care products (creams, cosmetics, deodorants, perfumes, polish for nails, etc.) containing many different chemicals, and often we have no idea what they are or what they might do to alter our health, no matter how beautiful they make us look and how good they make us smell. We dye our hair with chemicals and treat our hair with shampoos and conditioners that contain a variety of chemicals, often not even identified on the bottle because the mixture is proprietary.
We eat food that is often raised at distant places and depend on fossil fuels to get them to our local supermarket. Because we all like our fruits and vegetables to look perfect, they must be grown heavily treated with pesticides and fungicides, with herbicides added to keep the weeds under control. Since foods spoil over time, many fresh foods are treated with preservatives to make them look fresh even if they are not. Food additives are in almost every prepared product to reduce rate of spoilage and to improve color and flavor. There are some 3000 food additives in common usage. While our canned foods used to be in bare aluminum cans, we now line these cans with bisphenol A to avoid any metallic taste, assuming that the bisphenol A stays on the can. When we freeze our foods, we almost always place them in plastic, and we drink from plastic bottles and cups and assume that the plasticizers there, usually various phthalates or bisphenol A, do not leach into the food or drink.
It is not just fruits and vegetables that now contain chemicals that were not in them in earlier times. Now our meats come from animals treated with antibiotics and growth hormones. Our fish come from waters contaminated with persistent organic pollutants, such as bis[p-chlorophenyl]-1,1,1-trichloroethane (DDT) and its breakdown product, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), other pesticides, polychlorinated biphenyls (PCBs), methyl mercury, and even pharmaceuticals that are discharged into the waste water through human excretion and deposition of unused pharmaceuticals down the toilet. Many of the fish we eat come from fish farms, where fish are caged and fed food that often is contaminated with chemicals (Hites et al. 2004). In addition, in order to prevent infectious and fungal diseases in the enclosed, concentrated environment, antibiotics and fungicides must be used. Even the wild fish from lakes, streams, and the ocean contain organic chemicals, especially those that are lipophilic and persistent. The same contaminants, albeit usually at a lower concentration, are in our meats, eggs, and dairy products as a result of the contemporary practice of adding waste animal fats and products into the food fed to domestic farm animals. The feeding of waste animal fats to domestic animals that are not naturally carnivorous has resulted in the recycling of dangerous persistent chemicals like DDT and PCBs, which have not been produced in developed countries for more than 30 years, back into our food supply (IOM 2003).
Most people assume that the chemicals in carpets, in plastic food containers, and in drink bottles, and those sprayed under the kitchen sink to deal with insects stay put. However, it is clear that this is often not the case. Furthermore, most people assume that governments would not allow chemicals that might pose a hazard to health to be used. However, this also is often not the case. Unfortunately, chemicals volatilize from carpets and under-the-sink pesticide applications. They leach out of food and drink containers. Even before reaching the kitchen, there are chemicals in the food reflecting what the food animal ate or was treated with, and there are chemicals on the fruits and vegetables that are only partially removed by washing. So, a variety of organic chemicals are in the food and water we eat and drink and in the air we breathe, and are also absorbed through our skin.
Because infants and children are particularly vulnerable to harm from exposure to contaminants, there is special concern about the impact of pesticides in the diets of infants and children (NRC 1993). However, the mother's body is the first environment for the child, and the contaminants in the mother's body are passed to the fetus. Thus, efforts to reduce exposure to dangerous organics should focus on all women of reproductive age, not just infants and children.
Governments struggle to balance the promotion of new chemicals that will be useful to humankind with the protection of the public from hazards. The development and marketing of organic chemicals has increased enormously in a relatively brief period of time after World War II. In the United States, the Toxic Substance Control Act of 1976 (TSCA) is the law that presently regulates new chemicals. At present, there are more than 84,000 chemicals in this inventory, most of them organics. When the law was passed, most existing chemicals (62,000) were grandfathered into the inventory and were allowed to remain on the market without further study. Some chemicals were specifically identified to no longer be manufactured and used, as was the case with PCBs. New chemicals continue to be added to the inventory, but most of the testing of safety is dependent on the manufacturer. Figure 1.1 shows the distribution of chemicals currently on the market. Most are organics, although there are also some metals. To date, only about 250 chemicals have been rigorously tested independent of the industry by the Environmental Protection Agency (EPA), and only 5 have been regulated. In addition, TSCA (and thus EPA) does not have regulatory authority over pesticides, tobacco and tobacco products, radioactive materials, foods, food additives, drugs, and cosmetics, all of which are regulated by different government agencies. While new legislation is needed, a number of steps have been taken to prioritize chemicals of high use and those that are the most worrisome in terms of impacts on public health.
Figure 1.1. Approximately 100,000 individual chemicals have been registered for commercial use in the United States over the past 30 years. Chemical classes that receive the majority of public attention (e.g., pharmaceuticals, cosmetics and food additives, and pesticides) constitute only a small percentage of this inventory. Analytical methodologies are currently limited to several hundred of these nonregulated chemicals. Adapted from Muir and Howard (2006) with permission.
In 1999, the Canadian government implemented a tiered approach to address chemicals of concern in their inventory under the Canadian Environmental Protection Act. They evaluated 23,000 chemicals with a screen including physicochemical properties that might relate to persistence and bioaccumulation, measures of toxicity to various organ systems with consideration of acute, subchronic, and chronic endpoints. They identified 500 chemicals of high priority and 193 that required regulatory action. The government is continually reviewing the high-priority chemicals.
In late 2008, the European Chemical Agency, in preparation for the implementation of Registration, Evaluation, and Authorization of Chemicals (REACH), preregistered about 150,000 substances (http://www.echa.europa.eu/). The stated goal of REACH is “to improve the protection of human health and the environment through the better and earlier identification of the intrinsic properties of chemical substances.” It gives greater responsibility to industry to manage risks from chemicals and to provide safety information. It also has a goal of obtaining progressive substitution of the most dangerous chemicals when less dangerous alternatives are available. The provisions of REACH are to be phased in over a period of 11 years.
These actions by various governments are all intended to prevent chemicals, especially organic chemicals, from being produced and used before it is certain that they will not escape into the environment, lead to exposure to animals and people, and pose significant hazards to human health. However, the reality is that to do so is very difficult. Premarket tests usually look at acute lethality in animal models or study animal or human cells in culture. Investigation of the subtle effects on the nervous or immune systems and the delayed elevated risk of developing cancer is much more difficult and much more expensive. Even if this long-term testing is done in animal models, there is no certainty that humans will respond exactly the same. Thus, we all become guinea pigs for the effects of exposure to chemicals.
Another major problem is that most testing and understanding of the hazardous effects of chemicals in animal and cellular models are done one chemical at a time. But in the real world, each of us is constantly exposed to a very great mixture of chemicals. There is a mixture of chemicals in the air we breathe, a different mixture in the water or other fluids we drink, yet a different mixture in the food we eat and then we put yet other chemicals on or in our body through medications, lotions, shampoos, and other personal care products. However, interactions between the effects of two or more chemicals have been very poorly studied. There are three major possibilities—the effects of two chemicals may be additive, less than additive, or synergistic (Carpenter et al. 1998). Of particular concern is when there are synergistic effects.
To make things even more complex, the above-mentioned discussion assumes that one chemical has only one site of action. DDT, for example, kills insects by blocking the action potential in insect nerves and causing paralysis. This is the mechanism of action that kills pests. However, in humans, DDT does not block action potentials but increases the risk of a great variety of human diseases, including cancer, cardiovascular disease, diabetes, nervous systems effects, and changes in immune system function (detailed in the various chapters in this book). These different effects are certainly not mediated by actions at the neuronal sodium channel! And it is very unlikely that the effects on the different organ systems are mediated by the same mechanisms. This may involve different receptor binding sites or induction of different genes. Kiyosawa et al. (2008b) found that technical-grade DDT in rats induced genes associated with drug metabolism, cell proliferation and oxidative stress, and the nuclear receptors constitutive androstane receptor and pregnane X receptor. In another study, Kiyosawa et al. (2008a) reported that the pattern of gene induction in the mouse was significantly different from that in the rat to the same exposure. So one must conclude that any chemical that can induce genes regulating many different physiological functions has the potential to cause a great variety of different effects, but that there may be significant species differences which make extrapolation from animals to humans subject to errors.
These actions at different receptors and induction of a great variety of different genes likely explain the increasing frequency of demonstration of low-dose effects, nonlinear dose–response curves and what is commonly called “hormesis” (Calabrese 2008; Lee et al. 2010; Welshons et al. 2003). It has always been a tenant of toxicology that “the poison is in the dose.” This may well be true if the poison has a single binding site that leads to a single action, but it is clearly not true for the actions of many organics that have both multiple binding sites in different organ systems and also induce genes that alter many different physiological functions.
One book cannot hope to cover all organic chemicals or all possible biological effects. However, in this book, we have tried to consider effects on the major organ systems and the actions of representative chemicals for which there is at least some information. In many cases, the focus is on the persistent organic pollutants for the very practical reason that, because of their persistence, we have better exposure assessment and more information than is available for less persistent organics. As will be clear, our knowledge on the range of human health effects of organic chemicals is incomplete and much more research is needed.
References
Calabrese EF. 2008. Hormesis: 2008. Why it is important to toxicology and toxicologists. Environ Toxicol Chem 27:1451–1474.
Carpenter DO, Arcaro KF, Bush B, Niemi WD, Pang S, Vakharia DD. 1998. Human health and chemical mixtures: An overview. Environ Health Perspect 106(Suppl 6):1263–1270.
Hites RA, Foran JA, Carpenter DO, Hamilton MC, Knuth BA, Schwager SJ. 2004. Global assessment of organic contaminants in farmed salmon. Science 303:226–229.
IOM (Institute of Medicine). 2003. Dioxins and Dioxin-Like Compounds in the Food Supply: Strategies to Decrease Exposure. Washington, DC: National Academies Press.
Kiyosawa N, Kwekel JC, Burgoon LD, Dere E, Williams KJ, Tashiro C, et al. 2008a. Species-specific regulation of PXR/CAR/ER-target genes in the mouse and rat liver elicited by o,p′-DDT. BMC Genomics 9:487.
Kiyosawa N, Kwekel JC, Burgoon LD, Williams KJ, Tashiro C, Chittim B, et al. 2008b. o,p′-DDT elicits PXR/CAR-, not ER-, mediated responses in the immature ovariectomized rat liver. Toxicol Sci 101:350–363.
Lee DH, Steffes MW, Sjödin A, Jones RS, Needham LL, Jacobs DR, Jr. 2010. Low dose of some persistent organic pollutants predicts type 2 diabetes: A nested case-control study. Environ Health Perspect 118:1235–1242.
Muir DC, Howard PH. 2006. Are there other persistent organic pollutants? A challenge for environmental chemists. Environ Sci Technol 40:7157–7166.
NRC (National Research Council). 1993. Pesticides in the Diets of Infants and Children. Washington, DC: National Academies Press.
Welshons WV, Thayer KA, Judy BM, Taylor JA, Curran EM, vom Saal FS. 2003. Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. Environ Health Perspect 111:994–1006.
CHAPTER 2
Sources of Human Exposure
Background: Persistent and bioactive organic pollutants may reach the human body through different pathways, which usually determine subsequent health effects. Although occupational exposure has a prominent role, the environmental/dietary contact with these substances may be also very important. Therefore, it is critical not only to identify but also to estimate the contribution of each one of the exposure pathways.
Objectives: This chapter presents current calculation methods to estimate the main pathways of exposure to organic pollutants. Information regarding a few chemicals (persistent organic pollutants, pesticides, benzene, and perfluoroalkyl substances) is also summarized.
Discussion: Direct (or nondietary) exposure can be estimated as the sum of pollutant intake through air inhalation (air concentration related), as well as soil ingestion and dermal absorption (both dependent of soil concentration). In turn, dietary exposure can be calculated by considering food intake and water consumption. Dietary intake seems to be the main human exposure route to organic contaminants such as POPs or pesticides, with only a few exceptions. To a lesser extent, other pathways may have some notable contribution, especially for particular subgroups of population characterized by being more vulnerable to environmental pollutants, such as children or aged people.
Conclusions: Some basic tools to perform a first-tier screening for human health risk assessment, focusing on human exposure, are provided here. Food consumption seems to be the most important contributive route to the total intake of persistent and bioactive organic pollutants.
During normal life, people may be exposed to a broad range of chemicals through different pathways. Many contacts with those substances occur in an unconscious and/or involuntary manner during usual and daily activities. Indoor spaces are environments where the potential exposure to chemicals is especially significant. Moreover, occupational exposure to chemicals is also important for some adults during the working day. However, foodstuffs play a key role in the uptake of contaminants by humans. As it has been largely confirmed in recent years, dietary intake is the most critical pathway of exposure for many pollutant substances.
The effects of persistent and bioactive organic pollutants on human health are often dependent on the exposure routes through which those contaminants enter the human body. Therefore, it is critical to identify the main entrance pathways, as well as to estimate the contribution of each one. This information is essential to undertake actions to minimize the human exposure to organics, especially in those subpopulation groups for which the potential adverse health effects are more notable, such as children or the elderly.
This chapter is divided into two basic sections. The first one highlights current methods to estimate the main pathways of exposure to organic pollutants, while the second one compiles information for some specific chemicals, which are contemplated in subsequent chapters.
The U.S. National Research Council (NRC 1983), in its so-called Red Book, established a series of principles to be considered for human health risk assessment, defining it as a process in which information is analyzed to determine if an environmental hazard might cause harm to exposed persons and ecosystems. Human exposure was identified as a critical step in the original four-step risk assessment process. In recent years, scientists and governmental organizations have been encouraged to derive quick, easy, but robust mathematical tools to assess human exposure to environmental pollutants, considering that there exist diverse potential routes (dietary and nondietary) through which chemicals can enter the human body.
Inhalation occurs when chemical, radioactive, or physical pollutants enter the respiratory system, reaching the lungs. This may be a very important route of exposure, especially for some volatile chemicals and semivolatile organic compounds (SVOCs). This pathway has been found to be the most significant for volatile organic compounds (VOCs), such as benzene and formaldehyde, among others.
The U.S. Environmental Protection Agency (EPA) developed a specific methodology to assess exposure through inhalation (U.S. EPA 2009b). This approach, consistent with the inhalation dosimetry methodology, involves the estimation of exposure concentrations (ECs), instead of doses, for each receptor exposed to contaminants via inhalation in the risk assessment. ECs are time-weighted average concentrations derived from measured or modeled contaminant concentrations in air. The estimation of ECs is a prior step to the evaluation of noncancer risks (hazard quotient) or cancer risks. The recommended process for obtaining a specific EC value is the following: (1) to assess the duration of the exposure scenario, (2) to assess the exposure pattern of the exposure scenario, and (3) to estimate the scenario-specific EC. In the first step, the duration of the exposure scenario is chosen among three possibilities: acute, subchronic, or chronic. The second step entails comparing the exposure time and frequency at a site to that of a typical subchronic or chronic toxicity test. The third and final step involves estimating the EC for the specific exposure scenario based on the decisions made in steps 1 and 2. For subchronic and chronic exposures, EC is calculated according to the following equation:
where EC is the exposure concentration (mg/m3), CA is the concentration in air (mg/m3), ET is the exposure time (h/day), EF is the exposure frequency (day/year), ED is the exposure duration (years), and AT is the averaging time (years). Specific values of the parameters can be obtained from the scientific literature, including U.S. EPA reports. In case of acute exposure, EC would be equivalent to CA.
Contact with contaminated soils may become an important pathway of exposure to organic chemicals, posing large and long-lasting health risks, through different activities (e.g., through hand to mouth by young children, gardening by adults, and tracking of soil and dust into the home) (Kimbrough et al. 2010). In addition, for some classes of organic pollutants, such as persistent organic pollutants (POPs), incidental ingestion of contaminated soil has been pointed out as the major nondietary exposure pathway (Rostami and Juhasz 2011).
The U.S. EPA (1989) developed specific formulations for the estimation of the contribution of each nondietary pathway. The expression used to evaluate the exposure through ingestion (Exping, in mg/kg/day) is the following:
where CS is the concentration in soil (mg/kg), EF is the exposure frequency (day/year), IFP is the soil ingestion rate (mg/day), and BW is the body weight (kg).
Oral bioavailability is the fraction of an ingested contaminant that reaches the systemic circulation from the gastrointestinal tract. In turn, bioaccessibility, in relation to human exposure via ingestion, is defined as the fraction of a toxicant in soil that becomes soluble in the gastrointestinal tract, being then available for absorption (Guney et al. 2010). When data of bioavailability and/or bioaccessibility are unknown, worst-case scenarios are generally considered by assuming a value of 100%. In fact, a fraction of the contaminant may only be bioavailable, and therefore, this assumption may grossly overestimate the chemical daily intake, thereby influencing risk assessment (Rostami and Juhasz 2011).
Exposure to some indoor organic compounds through the dermal pathway is sometimes underestimated. Transdermal permeation can be substantially greater than is commonly assumed (Weschler and Nazaroff 2012).
When assessing exposure to organic pollutants through the dermal pathway, two different subroutes must be considered, as dermal contact may be relevant for chemicals contained in both water and soil (Ferré-Huguet et al. 2009; U.S. EPA 2009a). A generic formula is given for estimating the exposure through dermal contact (Expderm, in mg/kg/day):
where CS is the concentration in soil (mg/kg), AF is the adherence factor soil (mg/cm), ABS is the dermal absorption fraction (unitless), EF is the exposure frequency (day/year), SA is the surface area (cm2/day), and BW is the body weight (kg).
A summary of calculation equations to assess the human exposure through nondietary pathways is shown in Figure 2.1.
Figure 2.1. Main nondietary exposure pathway routes to persistent and bioactive organic pollutants. Calculation equations.
A number of studies have shown that dietary intake is the main entrance route of POPs and other organic chemicals to the human body (Cornelis et al. 2012; Domingo 2012b; Martí-Cid et al. 2008a; Perelló et al. 2012b), accounting for more than 90% of the total exposure (Linares et al. 2010; Noorlander et al. 2011). Therefore, the calculation of the total ingestion of pollutants through food consumption is essential to estimate the total amount of chemicals to which humans are exposed.
The ingestion of pollutants (Expdiet, in mg/kg/day) through food consumption is generally calculated as follows:
where FIR is the food ingestion rate (in kg/day), CF is the concentration in food (mg/kg), and BW is the body weight (kg). Thus, the daily intake of a chemical by a food group is estimated by multiplying the average concentration by the daily consumption of the food group. Finally, the estimated total dietary intake of each chemical is obtained by summing the respective intakes from each food group and dividing by the body weight.
Indoor exposure through the use of contaminated tap water is an issue of great concern (López et al. 2008). For certain chemicals, the water pathway may be especially significant, considering that adults may consume more than 2 L daily. Furthermore, water is a part of the nutritional basis of food ingestion by babies, as many baby foods are prepared by using drinking water, either tap or bottled. In any case, exposure to organic substances through water consumption must not be underestimated.
Similar to food, the intake of chemicals through water ingestion (Expwater, in mg/kg/day) is calculated by applying the following equation:
where WIR is the water ingestion rate (L/day), CF is the concentration in water (mg/L), and BW is the body weight (kg).