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Exposure to Toxic Environmental Agents
Epidemiological studies play an important role in quantifying how early life environmental chemical exposures influence the risk of childhood diseases. These studies face at least four major challenges that can produce noise when trying to identify signals of associations between chemical exposure and childhood health. Challenges include accurately estimating chemical exposure, confounding from causes of both exposure and disease, identifying periods of heightened vulnerability to chemical exposures, and determining the effects of chemical mixtures.
We provide recommendations that will aid in identifying these signals with more precision. PLoS Biol 15 12 : e Academic Editor: Linda S. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
The work is made available under the Creative Commons CC0 public domain dedication. Received by JMB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Environmental chemical exposures are ubiquitous yet largely invisible. In the United States, over 85, chemicals are used in commerce, and thousands of these are produced in quantities of over one million pounds per year [ 1 ].
During our lives, we are exposed to many known toxicants, as well as numerous potentially hazardous chemicals with less well-characterized risks. These chemicals are detected in the blood and urine of almost every person in the US, as well as people in other countries [ 2 ]. Broad generalizations about these chemicals are difficult, but they can be categorized based on their uses in commerce e. The potential toxicity of the vast majority of these chemicals is not routinely evaluated before they are introduced into commerce or industry [ 3 ].
While recent US legislation mandates assessments of the health effects of the most concerning of these chemicals [ 4 ], the scale of this problem is daunting given the large number of chemicals used and wide range of potential effects they could have on human health and development.
Quantifying the risk that chemicals pose to human health is of great interest to scientists, the public, policy makers, and regulators. Studies using laboratory animals, in vitro models, high-throughput screening, and human populations all provide valuable information when assessing the risks that chemicals pose to human health. Epidemiological studies provide estimates of the health risks of chemical exposures in human populations and primarily rely on observational data, as it would be unethical to experimentally assign chemical exposures to humans.
Epidemiological studies are not without challenges, and these challenges can be thought of as a signal-to-noise ratio problem. There is particular concern that exposure to some chemicals during gestation, infancy, or childhood may increase the risk of obesity, asthma or allergies, or neurodevelopmental disorders [ 5 ]. These chemicals include pesticides e. Concern over chemical exposures during fetal, infant, and child development arises for several reasons.
First, infants and children may have higher exposure to some chemicals than adults because they consume more water and greater quantities of specific foods, rely solely on breast milk or formula for the first months of life, and have higher ventilation rates, intestinal absorption, surface area-to-volume ratios, and hand-to-mouth activity [ 6 ].
In addition, the time-dependent and synchronized nature of their rapidly developing organ systems makes them more sensitive to environmental inputs that disrupt growth and development. Finally, the fetus, infant, and child may have higher chemical body burdens for a given dose of exposure because they have different pharmacokinetics compared to adults, which might alter the absorption and distribution of chemicals and decrease their capacity to metabolize and excrete chemicals. Epidemiologists face at least four major challenges when estimating the potential effect of chemical exposures on child health; these include estimating chemical exposure, confounding, identifying periods of heightened vulnerablity, and chemical mixtures.
Each of these challenges represents a source of noise in epidemiological studies that must be minimized in order to identify signals. Often, there is concern that this noise could result in the declaration of an adverse effect when one truly does not exist i. However, it is equally important to note that noise could produce false negatives, where we miss the true effect of a chemical exposure.
Measuring environmental chemical exposures in epidemiological studies requires valid and reliable assessment methods. Chemical exposures can be assessed through questionnaires, geospatial databases, environmental sampling, personal monitoring, or biomarkers. Biomarkers provide objective and quantitative estimates of absorbed chemical exposure, and hundreds of chemicals can be sensitively and specifically measured in a variety of biospecimens, including blood, urine, breast milk, hair, and toenail clippings [ 7 ].
These biomarkers can include the exposure of interest or metabolites that are formed after ingestion. For instance, the organochlorine pesticide dichlorodiphenytrichloroethane is metabolized into dichlorodiphenyldichlorethylene, and concentrations of both can be measured in serum.
While there is currently great enthusiasm for using biomarkers to assess chemical exposures, care must be taken to consider potential sources of bias in biomarker values, including differences in metabolism with disease state or age and exogenous contamination during sample collection, storage, processing, and analysis [ 8 , 9 ]. Generally, chemicals that have long biological half-lives—on the order of months for lead and years for persistent chemicals—are measured in blood or serum and represent recent and past exposures.
Chemicals with short biological half-lives—on the order of less than 24 hours for phthalates, phenols, and nonpersistent pesticides—are measured in urine and reflect exposure in the last few days. Errors in determining whether a person or population has been exposed to a given chemical, known as exposure misclassification, can distort links between exposure and outcomes. Assessing exposure to nonpersistent chemicals can be challenging because of their short biological half-lives and the episodic nature of exposure.
For example, BPA is a potential endocrine disruptor with a biological half-life of approximately six hours that is found in some polycarbonate plastics and resins, food can linings, medical devices, and thermal receipts [ 10 ]. Because of its short biological half-life and the variable nature of BPA exposure, there is considerable within-person variation in urinary BPA concentrations relative to differences between people. When exposure misclassification occurs randomly among all people in a study regardless of disease outcome, then exposure misclassification is said to be nondifferential.
Given that the basis of epidemiological studies is comparisons in health status between groups of individuals with different levels of exposure, nondifferential exposure misclassification creates noise in the data, drowning out potential signals and possibly creating false negative results. The x-axis denotes the sequential number of the collected urine sample.
The figure illustrates that a single randomly chosen sample from an individual may not represent their average exposure and could misclassify them as having lower or higher exposure than their true exposure. Moreover, a single urine sample cannot reliably distinguish differences in BPA concentrations between individuals because the within-person variation in BPA concentrations is greater than the between-person variation.
BPA, bisphenol A. It is important to note that exposure misclassification exists as a continuum and not as an all-or-none phenomenon. Thus, misclassification is generally more common with nonpersistent exposures arising from dietary sources than with nonpersistent exposures where the source of exposure is more stable over time.
The latter includes chemical exposures found in personal care products e. Work by Perrier et al. They show that, for chemicals with substantial within-person variation e. For chemicals with more moderate within-person misclassification e.
One way to address the issues related to exposure misclassification of nonpersistent compounds is to pool multiple urine samples collected from individuals, as originally recommended by Perrier et al.
This is a cost-effective solution, as it negates the need to conduct assays on dozens of urine samples and then take the average; instead, the pooled sample provides the arithmetic average of those samples while only requiring a single assay to be conducted per participant.
Another potential solution is to measure concentrations of chemicals in shed deciduous teeth, toenail clippings, or hair [ 14 ]. These matrices are appealing when studying the health effects of chronic exposures, since some environmental agents, like heavy metals, accumulate in these slow-growing tissues over time and they can be noninvasively collected [ 15 ].
Thus, chemical concentrations in these matrices can provide a time-integrated exposure metric due to continuous incorporation of the chemical into the tissue. When conducting observational studies, it is possible that we misattribute the increased risk of disease to the environmental agent being studied when another factor that causes both exposure and disease risk is the real causal factor. This phenomenon, known as confounding, can arise when one or more determinants of health are also determinants of exposure.
Many of these factors associated with disease risk are often also associated with environmental chemical exposures. For example, suppose we observed that BPA exposure is associated with increased risk of childhood obesity. However, BPA is found in some food packaging and children who have higher risk of becoming obese might consume more packaged food that is less nutritious and more calorically dense than those children who do not consume as much packaged food Fig 2A.
Thus, failure to adjust for packaged food intake might lead us to falsely declare BPA a risk factor for obesity when the observation is really due to the calorically dense diet. Hypothetical relations between A bisphenol A exposure, packaged food consumption, and obesity risk and B prenatal mercury exposure, fish consumption, and brain development. In panel A, a study is investigating whether bisphenol A is associated with increased risk of obesity and packaged food intake is associated with greater bisphenol A exposure and higher obesity risk.
This is an example of positive confounding, where adjusting for packaged food consumption will cause the association between bisphenol A exposure and obesity to become weaker.
In Panel B, we are investigating whether mercury exposure is associated with adverse brain development and fish consumption is associated with greater mercury exposure and better brain development. This is an example of negative confounding, and adjusting for fish consumption will make the association between mercury exposure and brain development stronger. This less-appreciated form of confounding can arise when the confounding factor is associated with better health outcomes and higher levels of exposure.
For example, prenatal mercury exposure was adversely associated with some aspects of child brain development, but only after adjusting for fish intake or serum polyunsaturated fatty acid concentrations during pregnacy Fig 2B [ 16 , 17 ]. This is because some fish are a source of both mercury and micronutrients that are beneficial to fetal brain development, and the effect of fish on both mercury and brain development obscured the effects of mercury on brain development.
Negative confounding could also arise in studies of infant exposure to persistent chemicals in breast milk, as breast milk is a source of exposure to these chemicals and associated with many infant and child health outcomes. It is imperative to note that it is not appropriate to adjust for variables that are both causes of exposure and childhood health. For instance, prenatal perfluoroalkyl substance PFAS exposures are associated with increased risk of childhood obesity [ 5 ]. Some might argue that it is necessary to adjust for birth weight, since birth weight is a determinant of childhood obesity risk [ 18 ].
However, since PFAS exposure is also associated with reduced birth weight, this adjustment will remove the effect that PFAS has on obesity through its association with birth weight. Thus, the association adjusted for birth weight will no longer reflect the total effect that PFAS has on the risk of obesity.
In order to avoid this potential source of bias, confounding factors should be selected based on subject matter knowledge and not solely on statistical grounds. Addressing confounding in epidemiological studies requires careful planning during the study design phase to ensure that important confounding factors are measured with valid and reliable instruments and are accounted for using appropriate methods [ 19 ].
Fortunately, most well-designed epidemiological studies studying environmental chemical exposures have carefully considered, collected, and adjusted for known confounding factors [ 20 ]. The toxicity of some environmental chemicals may depend on the timing of exposure.
The idea of discrete periods of heightened vulnerability has its origins in the study of teratogens, whose effects are present only when the exposure occurs during a specific period of fetal development [ 21 ]. One of the most infamous teratogens is thallidomide, a pharamaceutical agent used in the s and s to treat nausea in pregnant women. Thallidomide caused limb defects in thousands of children born to women who used the drug [ 22 ].
Notably, the presence of limb defects depended on the timing of thalidomide use, where exposure between 21 and 36 days after conception was necessary to cause these birth defects. This notion of developmentally sensitive periods of development has been extended to include health outcomes that manifest later in life and is referred to as the Developmental Origins of Adult Health and Disease hypothesis [ 23 ]. One of the first examples of an exposure with both a discrete period of heightened vulnerability and long-term health effects was diethylstilbestrol DES , a pharmaceutical given to women from the s—s to prevent spontaneous abortion.
Daughters born to women who were presecribed DES in the first half of their pregnany had increased risk of developing vaginal or cervical clear cell adenocarcinoma [ 24 ], as well as reproductive problems and some cancers [ 25 ]. The examples of thallidomide and DES highlight the challenges that epidemiological studies face when trying to identify periods of heightened vulnerability to early life chemical exposures.
If there are discrete periods of vulnerability to chemical exposures during development, then this can be a source of noise, because researchers must measure exposure during that specific period in order to observe an association. Identifying periods of heightened vulnerability to a specific exposure can be challenging, as we often do not know if and when they exist.
Thus, a lack of association between an environmental chemical exposure and child health may arise when exposure was not assessed during the etiologically relevant period. While there has been justifiable emphasis on studying the toxicity of chemical exposures during fetal development, there are other potential periods of heightened vulnerability to environmental chemical exposure that likely depend on the specific chemical and health outcome of interest.
An emerging body of evidence suggests that chemical and nonchemical exposures before conception may adversely affect the oocyte or sperm, which in turn may cause changes in the health status of the offspring via epigenetic reprogramming [ 26 , 27 ]. Periods of heightened vulnerability continue into infancy and childhood.
Health Effects from Chemical Exposure
Read terms. The Program on Reproductive Health and the Environment endorses this document. This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. This information should not be construed as dictating an exclusive course of treatment or procedure to be followed. ABSTRACT: Reducing exposure to toxic environmental agents is a critical area of intervention for obstetricians, gynecologists, and other reproductive health care professionals. Patient exposure to toxic environmental chemicals and other stressors is ubiquitous, and preconception and prenatal exposure to toxic environmental agents can have a profound and lasting effect on reproductive health across the life course.
Nearly every activity leaves behind some kind of waste in the environment. Households create ordinary garbage. Cars, trucks, and buses emit exhaust gases while in operation. Industrial and manufacturing processes create solid and hazardous waste. Some wastes contain chemicals that are hazardous to people and the environment.
I agreed to review this book because I assumed from the title that it would contain some analytical content—a book on human exposure must, I thought, surely, include some chemical analysis. If it does, it is well hidden. The book is, instead, an encyclopaedic collection of non-occupational levels of toxicants likely to be encountered, and toxicity data associated with these; if analysis of the toxicants had been covered in the same depth the book would have been at least twice the size. According to the same publicity it is written by leading environmental health scientists. The book contains 30 chapters and the criteria used to arrange these, if any, are not obvious.
Epidemiological studies play an important role in quantifying how early life environmental chemical exposures influence the risk of childhood diseases. These studies face at least four major challenges that can produce noise when trying to identify signals of associations between chemical exposure and childhood health. Challenges include accurately estimating chemical exposure, confounding from causes of both exposure and disease, identifying periods of heightened vulnerability to chemical exposures, and determining the effects of chemical mixtures. We provide recommendations that will aid in identifying these signals with more precision. PLoS Biol 15 12 : e Academic Editor: Linda S.
Кнопка на полу привела ее в движение, и дверь, издав шипящий звук, отъехала в сторону. Чатрукьян ввалился в комнату. - Коммандер… сэр, я… извините за беспокойство, но монитор… я запустил антивирус и… - Фил, Фил, - нехарактерным для него ласковым тоном сказал Стратмор. - Потише и помедленнее.
Vulnerable Populations and Environmental Disparities
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Выходит, это не клиент. - Вы хотите сказать, что нашли этот номер. - Да, я сегодня нашел в парке чей-то паспорт. Ваш номер был записан на клочке бумаги и вложен в паспорт. Я было подумал, что это номер гостиницы, где тот человек остановился, и хотел отдать ему паспорт. Но вышла ошибка. Я, пожалуй, занесу его в полицейский участок по пути в… - Perdon, - прервал его Ролдан, занервничав.
Дэвид Беккер умрет. Халохот поднимался вверх с пистолетом в руке, прижимаясь вплотную к стене на тот случай, если Беккер попытается напасть на него сверху. Железные подсвечники, установленные на каждой площадке, стали бы хорошим оружием, если бы Беккер решил ими воспользоваться. Но если держать дистанцию, можно заметить его вовремя. У пистолета куда большая дальность действия, чем у полутораметрового подсвечника. Халохот двигался быстро, но осторожно. Ступени были настолько крутыми, что на них нашли свою смерть множество туристов.
Клушару эта идея понравилась. Он сел в кровати.
Массажистка быстро убрала руки из-под полотенца. В дверях появилась телефонистка и поклонилась: - Почтенный господин. - Слушаю. Телефонистка отвесила еще один поклон: - Я говорила с телефонной компанией. Звонок был сделан из страны с кодом один - из Соединенных Штатов.
Итак, ТРАНСТЕКСТ вскрывает один шифр в среднем за шесть минут. Последний файл обычно попадает в машину около полуночи. И не похоже, что… - Что? - Бринкерхофф даже подпрыгнул. Мидж смотрела на цифры, не веря своим глазам.
Мидж горящими глазами смотрела ему вслед. - О нет, можешь, - прошептала. И, повернувшись к Большому Брату, нажатием клавиши вызвала видеоархив. Мидж это как-нибудь переживет, - сказал он себе, усаживаясь за свой стол и приступая к просмотру остальных отчетов.
Он медленно потянул к себе микрофон. В то же самое мгновение Сьюзан опять бросила взгляд на руку Танкадо, на этот раз посмотрев не на кольцо… не на гравировку на золоте, а на… его пальцы. Три пальца. Дело было вовсе не и кольце, a в человеческой плоти.