Environmental health criteria 237: Principles for evaluating health risks in children associated with exposure to chemicals
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Environmental factors play a major role in determining the health and well-being of children.1 Accumulating evidence indicates that children, who comprise over one third of the world%27s population, are among the most vulnerable of the world%27s population and that environmental factors can affect children%27s health quite differently from adults%27 health. Poor, neglected, and malnourished children suffer the most. These children often live in unhealthy housing, lack clean water and sanitation services, and have limited access to health care and education. One in five children in the poorest parts of the world will not live to their fifth birthday, mainly because of environment-related diseases. The World Health Organization (WHO) estimates that over 30%25 of the global burden of disease in children can be attributed to environmental factors. Health is determined by a variety of factors. In addition to the physical environment, genetics, and biology, social, economic, and cultural factors play major roles. Although it is critical to understand the various driving forces during childhood that shape health and behaviour throughout life, the emphasis of this document is specifically on exposure to environmental chemicals. This document evaluates the scientific principles to be considered in assessing health risks in children from exposures to environmental chemicals during distinct developmental stages and provides information for public health officials, research and regulatory scientists, and other experts responsible for protecting children%27s health. The central focus of this document is on the developmental stage rather than on a specific environmental chemical or a specific disease or outcome. Developmental stage-specific periods of susceptibility have been referred to as critical windows for exposure or critical windows of development. These distinct life stages are defined by relevant dynamic processes occurring at the molecular, cellular, organ system, and organism level. It is the differences in these life stages along with exposures that will define the nature and severity of environmental impacts. Children have different susceptibilities during different life stages owing to their dynamic growth and developmental processes as well as physiological, metabolic, and behavioural differences. From conception through adolescence, rapid growth and developmental processes occur that can be disrupted by exposures to environmental chemicals. These include anatomical, physiological, metabolic, functional, toxicokinetic, and toxicodynamic processes. Exposure pathways and exposure patterns may also be different in different stages of childhood. Exposure can occur in utero through transplacental transfer of environmental agents from mother to fetus or in nursing infants via breast milk. Children consume more food and beverages per kilogram of body weight than do adults, and their dietary patterns are different and often less variable during different developmental stages. They have a higher inhalation rate and a higher body surface area to body weight ratio, which may lead to increased exposures. Children%27s normal behaviours, such as crawling on the ground and putting their hands in their mouths, can result in exposures not faced by adults. Children%27s metabolic pathways may differ from those of adults. Children have more years of future life and thus more time to develop chronic diseases that take decades to appear and that may be triggered by early environmental exposures. They are often unaware of environmental risks and generally have no voice in decision-making. The accumulating knowledge that children may be at increased risk at different developmental stages, with respect to both biological susceptibility and exposure, has raised awareness that new risk assessment approaches may be necessary in order to adequately protect children. Traditional risk assessment approaches and environmental health policies have focused mainly on adults and adult exposure patterns, utilizing data from adult humans or adult animals. There is a need to expand risk assessment paradigms to evaluate exposures relevant to children from preconception to adolescence, taking into account the specific susceptibilities at each developmental stage. The full spectrum of effects from childhood exposures cannot be predicted from adult data. Risk assessment approaches for exposures in children must be linked to life stages. A broad spectrum of diseases in children are known (or suspected) to be associated with unhealthy environments. For much of the world, traditional environmental health hazards continue to remain the primary source of ill-health. These include lack of adequate nutrition, poor sanitation, contaminated water, rampant disease vectors (e.g. mosquitoes and malaria), and unsafe waste disposal. In addition, rapid globalization and industrialization coupled with unsustainable patterns of production and consumption have released large quantities of chemical substances into the environment. Although the term environmental exposure can encompass a variety of factors, the focus of this document is specifically on environmental chemical exposures. Most of these substances have not been assessed for potential toxicity to children, nor have the most vulnerable subpopulations of children been identified. The incidence of a number of important paediatric diseases and disorders (e.g. asthma, neurobehavioural impairment) is increasing in several parts of the world. Although a variety of factors are likely to be involved, this may be due, in part, to the quality of the environment in which children live, grow, and play. Establishing causal links between specific environmental exposures and complex, multifactorial health outcomes is difficult and challenging, particularly in children. For children, the stage in their development when the exposure occurs may be just as important as the magnitude of exposure. Very few studies have characterized exposures during different developmental stages. Examples have shown that exposures to the same environmental chemical can result in very different health outcomes in children compared with adults. Some of these outcomes have been shown to be irreversible and persist throughout life. Furthermore, different organ systems mature at different rates, and the same dose of an agent during different periods of development can have very different consequences. There may also be a long latency period between exposure and effects, with some outcomes not apparent until later in life. Some examples of health effects resulting from developmental exposures include those observed prenatally and at birth (e.g. miscarriage, stillbirth, low birth weight, birth defects), in young children (e.g. infant mortality, asthma, neurobehavioural and immune impairment), and in adolescents (e.g. precocious or delayed puberty). Emerging evidence suggests that an increased risk of certain diseases in adults (e.g. cancer, heart disease) can result in part from exposures to certain environmental chemicals during childhood. While research has addressed the impact of environmental chemicals on children%27s health, typically investigators have focused on exposure to a particular environmental chemical, such as heavy metals or pesticides, and a particular organ system or end-point. Noticeably absent are prospective longitudinal studies capturing exposures over key developmental windows or life stages. Virtually no studies have captured periconceptional exposures either alone or in addition to other life stage exposures. Advancing technology and new methodologies now offer promise for capturing exposures during these critical windows. This will enable investigators to detect conceptions early and estimate the potential competing risk of early embryonic mortality when considering children%27s health outcomes that are conditional upon survival during the embryonic and fetal periods. The special vulnerability of children should form the basis for development of child-protective policies and risk assessment approaches. A lack of full proof for causal associations should not prevent efforts to reduce exposures or implement intervention and prevention strategies.
Environmental factors play a major role in determining the health and well-being of children.1 Accumulating evidence indicates that children, who comprise over one third of the world's population, are among the most vulnerable of the world's population and that environmental factors can affect children's health quite differently from adults' health. Poor, neglected, and malnourished children suffer the most. These children often live in unhealthy housing, lack clean water and sanitation services, and have limited access to health care and education. One in five children in the poorest parts of the world will not live to their fifth birthday, mainly because of environment-related diseases. The World Health Organization (WHO) estimates that over 30%25 of the global burden of disease in children can be attributed to environmental factors. Health is determined by a variety of factors. In addition to the physical environment, genetics, and biology, social, economic, and cultural factors play major roles. Although it is critical to understand the various driving forces during childhood that shape health and behaviour throughout life, the emphasis of this document is specifically on exposure to environmental chemicals. This document evaluates the scientific principles to be considered in assessing health risks in children from exposures to environmental chemicals during distinct developmental stages and provides information for public health officials, research and regulatory scientists, and other experts responsible for protecting children's health. The central focus of this document is on the developmental stage rather than on a specific environmental chemical or a specific disease or outcome. Developmental stage-specific periods of susceptibility have been referred to as critical windows for exposure or critical windows of development. These distinct life stages are defined by relevant dynamic processes occurring at the molecular, cellular, organ system, and organism level. It is the differences in these life stages along with exposures that will define the nature and severity of environmental impacts. Children have different susceptibilities during different life stages owing to their dynamic growth and developmental processes as well as physiological, metabolic, and behavioural differences. From conception through adolescence, rapid growth and developmental processes occur that can be disrupted by exposures to environmental chemicals. These include anatomical, physiological, metabolic, functional, toxicokinetic, and toxicodynamic processes. Exposure pathways and exposure patterns may also be different in different stages of childhood. Exposure can occur in utero through transplacental transfer of environmental agents from mother to fetus or in nursing infants via breast milk. Children consume more food and beverages per kilogram of body weight than do adults, and their dietary patterns are different and often less variable during different developmental stages. They have a higher inhalation rate and a higher body surface area to body weight ratio, which may lead to increased exposures. Children's normal behaviours, such as crawling on the ground and putting their hands in their mouths, can result in exposures not faced by adults. Children's metabolic pathways may differ from those of adults. Children have more years of future life and thus more time to develop chronic diseases that take decades to appear and that may be triggered by early environmental exposures. They are often unaware of environmental risks and generally have no voice in decision-making. The accumulating knowledge that children may be at increased risk at different developmental stages, with respect to both biological susceptibility and exposure, has raised awareness that new risk assessment approaches may be necessary in order to adequately protect children. Traditional risk assessment approaches and environmental health policies have focused mainly on adults and adult exposure patterns, utilizing data from adult humans or adult animals. There is a need to expand risk assessment paradigms to evaluate exposures relevant to children from preconception to adolescence, taking into account the specific susceptibilities at each developmental stage. The full spectrum of effects from childhood exposures cannot be predicted from adult data. Risk assessment approaches for exposures in children must be linked to life stages. A broad spectrum of diseases in children are known (or suspected) to be associated with unhealthy environments. For much of the world, traditional environmental health hazards continue to remain the primary source of ill-health. These include lack of adequate nutrition, poor sanitation, contaminated water, rampant disease vectors (e.g. mosquitoes and malaria), and unsafe waste disposal. In addition, rapid globalization and industrialization coupled with unsustainable patterns of production and consumption have released large quantities of chemical substances into the environment. Although the term environmental exposure can encompass a variety of factors, the focus of this document is specifically on environmental chemical exposures. Most of these substances have not been assessed for potential toxicity to children, nor have the most vulnerable subpopulations of children been identified. The incidence of a number of important paediatric diseases and disorders (e.g. asthma, neurobehavioural impairment) is increasing in several parts of the world. Although a variety of factors are likely to be involved, this may be due, in part, to the quality of the environment in which children live, grow, and play. Establishing causal links between specific environmental exposures and complex, multifactorial health outcomes is difficult and challenging, particularly in children. For children, the stage in their development when the exposure occurs may be just as important as the magnitude of exposure. Very few studies have characterized exposures during different developmental stages. Examples have shown that exposures to the same environmental chemical can result in very different health outcomes in children compared with adults. Some of these outcomes have been shown to be irreversible and persist throughout life. Furthermore, different organ systems mature at different rates, and the same dose of an agent during different periods of development can have very different consequences. There may also be a long latency period between exposure and effects, with some outcomes not apparent until later in life. Some examples of health effects resulting from developmental exposures include those observed prenatally and at birth (e.g. miscarriage, stillbirth, low birth weight, birth defects), in young children (e.g. infant mortality, asthma, neurobehavioural and immune impairment), and in adolescents (e.g. precocious or delayed puberty). Emerging evidence suggests that an increased risk of certain diseases in adults (e.g. cancer, heart disease) can result in part from exposures to certain environmental chemicals during childhood. While research has addressed the impact of environmental chemicals on children's health, typically investigators have focused on exposure to a particular environmental chemical, such as heavy metals or pesticides, and a particular organ system or end-point. Noticeably absent are prospective longitudinal studies capturing exposures over key developmental windows or life stages. Virtually no studies have captured periconceptional exposures either alone or in addition to other life stage exposures. Advancing technology and new methodologies now offer promise for capturing exposures during these critical windows. This will enable investigators to detect conceptions early and estimate the potential competing risk of early embryonic mortality when considering children's health outcomes that are conditional upon survival during the embryonic and fetal periods. The special vulnerability of children should form the basis for development of child-protective policies and risk assessment approaches. A lack of full proof for causal associations should not prevent efforts to reduce exposures or implement intervention and prevention strategies.
