Children interact with the physical environment differently than adults, and are uniquely susceptible to environmental toxicants. Routes of absorption, distribution, metabolism, and target organ toxicities vary as children grow and develop. This article summarizes the sources of exposure and known adverse effects of toxicants that are ubiquitous in our environment, including tobacco smoke, ethanol, solvents, heavy metals, volatile organic compounds, persistent organic pollutants, and pesticides. Preventive strategies that may be used in counseling children and their families are highlighted.
Key points
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Susceptibility to environmental toxicants depends on a child’s developmental stage and interactions within the physical, biological, and social environment.
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Critical stages of growth and cellular differentiation that occur in fetuses, newborns, infants, and children represent periods of greatest vulnerability to the adverse effects of environmental toxicants.
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The floor inside the home represents an important microenvironment for young children, because their breathing zones are lower than those of adults, and many chemicals are concentrated near the floor. Ingestion, inhalation, and dermal absorption can occur.
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Toxicants are widely dispersed in the environment. It is important for pediatricians to understand the potential routes of exposure, toxic effects, and strategies for prevention of exposure in order to provide anticipatory guidance to children and their families.
Overview and developmental aspects
Introduction
Toxicants are ubiquitous in the human environment, and children are often inadvertently exposed. Infants and children are a uniquely vulnerable population, especially during early stages of growth and development. Exposure to environmental toxicants is affected by children’s physical, biological, and social environment. Children and adults experience the physical environment differently. The physical environment can be more hazardous for children, especially those who are preambulatory and lack control of their surroundings. The physical environment changes as children gain independence and spend time away from the home. The biological environment is determined by genotypic and metabolic responses to interactions with the physical environment. Routes of absorption, metabolism, distribution, and health effects vary, and are influenced by the developmental stage in which exposure occurs. A toxicokinetic diagram illustrates how environmental toxins interact with the biological environment ( Fig. 1 ). The social environment is determined by lifestyle preferences and societal regulations and policies that influence the physical environment.
The Epigenome
The epigenome refers to biochemical interactions that regulate expression of the genome without modification of DNA sequence. The epigenome is heritable, and highly vulnerable to toxicants during periods of rapid growth, such as fetal embryogenesis. DNA methylation is a well-described epigenetic mechanism that affects DNA expression. When the promoter region of DNA is methylated, it remains tightly coiled, affecting DNA transcription. Impaired DNA methylation in children is associated with exposure to toxicants, such as lead and polycyclic aromatic hydrocarbons (PAHs) found in cigarette smoke and motor vehicle exhaust.
Preconception
Even before conception, environmental toxins can influence future offspring. Oogonia differentiate during fetal life and therefore become vulnerable to toxicants during fetal development. Spermatogenesis begins at puberty; thus sperm become susceptible after puberty, in the periconceptual period. Because sperm lack DNA repair mechanisms and differentiate rapidly, they are highly vulnerable to toxins. Impaired fertility is a known consequence of environmental exposures. Examples of toxicants known to affect fertility include cigarette smoke and diethylstilbestrol (DES). DES is an EDS that was prescribed to pregnant women until the 1970s to prevent miscarriage. Daughters of women exposed to DES developed vaginal clear cell carcinoma and infertility. Transgenerational effects include premature birth of DES grandchildren and hypospadias in DES grandsons. Some environmental exposures occurring long before conception can affect future pregnancy. Certain toxins bioaccumulate before conception, and mobilize because of physiologic changes during pregnancy that promote elimination. Polychlorinated biphenyls (PCBs) are lipid-soluble organohalogens used to manufacture electrical equipment before their ban in the 1970s. PCBs are highly stable in the environment, and are stored in adipose tissue. Lead is a heavy metal that bioaccumulates in bone, and is mobilized during pregnancy because of high calcium turnover. Both PCBs and lead are known fetal neurotoxicants.
The Fetus
Maternal exposures occurring during pregnancy can result in congenital malformations and fetal loss. The fetus is highly susceptible within critical stages of development, such as fetal organogenesis (weeks 3–8 of gestation). Exposure to neurotoxins during neuronal differentiation, proliferation, migration, and myelination can lead to permanent neuronal loss, and affects future neurocognitive function. For example, exposure to ionizing radiation at less than 18 weeks’ gestation is correlated with microcephaly and neurocognitive delay. Certain properties permit chemicals to cross the placental barrier and reach the fetus, such as low molecular weight, lipid solubility, and ability to use placental active transport mechanisms. Carbon monoxide is an example of a low-molecular-weight compound that is found in cigarette smoke, and is transported across the placenta via passive diffusion. Lipophilic compounds, such as ethanol, PAHs, and PCBs, also cross the placenta and can bioaccumulate in the fetus. Fetal exposures can be measured at birth via cord blood and meconium sampling.
Newborns
Breast milk and formula represent important sources of exposure in newborns. Lipid-soluble toxicants, such as dioxin, PCBs, and organochlorine pesticides, are stored in maternal adipose and concentrated in breast milk. Newborns fed formula may be exposed to toxins in the water supply, such as lead, arsenic, and nitrates. Nitrates are found in fertilizer and pesticides, and can contaminate soil and groundwater. Cases of methemoglobinemia have been reported in infants following exposure to nitrates from drinking water. Infants less than 3 months old are at greater risk for methemoglobinemia than older children. Newborn skin is highly permeable, has a large surface/volume ratio, and is an important site of absorption of lipophilic compounds. Organs in which rapid cell division continues remain highly susceptible to toxicants. Neuronal cell division is complete by 6 months, but migration, differentiation, and myelination continue into adolescence. A newborn’s body fat composition affects distribution of lipid-soluble toxicants. Mean body fat increases with advancing gestational age, and female infants tend to have a greater percentage body fat. Infants with lower body fat levels have limited distribution of lipophilic compounds, whereas large-for-gestational-age infants with greater fat stores are more likely to sequester lipid-soluble toxicants. Hepatic enzymes that metabolize toxicants are developmentally regulated, and are subject to genetic polymorphisms at all developmental stages. At birth, glomerular filtration is a fraction of adult values, and slowly increases over the first year of life.
Infants and Toddlers
Increasing ability to interact with the physical environment influences exposures during this stage. Behaviors such as oral exploration and introduction of solid foods also contribute. Processed baby foods may contain additives such as coloring, flavoring, or preservatives; safe levels of these additives are typically based on lifetime exposure in adults. Baby foods may also be contaminated by toxicants such as bisphenol-A (BPA; a plasticizer) or pesticide residue. The Food Quality Protection Act (FQPA) of 1996 provides age-appropriate safety standards for pesticide exposure based on children’s dietary patterns. The FQPA requires the US Environmental Protection Agency (EPA) to account for other sources, such as drinking water and residential application, and for cumulative effects of pesticides with common mechanisms of action. The EPA uses a 10-fold margin of safety when setting standards when there are limited data available for children. Infants have higher respiratory rate, resting metabolic rate, and greater oxygen consumption than older children and adults. This higher rate correlates with a proportionally higher inhaled toxicant exposure into smaller airways and lung surface area. During infancy, the ratio of skin surface area to body weight is twice that of adults. Therefore, the skin remains an important site of absorption. The floor inside the home is an important microenvironment for infants and toddlers. Surface contaminants, such as pesticides and volatile organic compounds (VOCs), are concentrated near the ground; oral, respiratory, or percutaneous exposures can occur while crawling or playing on the floor. Formaldehyde is a VOC that is a known carcinogen. Formaldehyde levels are much greater indoors than outdoors, and are significantly higher following installation of new synthetic carpet or pressed wood cabinets. PAHs are another carcinogenic VOC, found in cigarette smoke and concentrated in house dust.
Preschool and School-Aged Children
During this stage, food remains an important source of exposure. Children require more calories for growth than adults, increasing quantitative risk. Qualitative differences in diet are also seen, with greater consumption of foods that may be contaminated with pesticides (fruits, vegetables, meat, and dairy). In 2014, the Environmental Working Group published lists of fruits and vegetables most likely to contain pesticide residue, termed the Dirty Dozen. The so-called Clean Fifteen are least likely to contain pesticide residue. Children have higher minute ventilation than adults, and are more vulnerable to inhaled air pollutants. Breathing zones affect exposure to inhaled toxicants in young children. For adults, the typical breathing zone is approximately 120 to 180 cm (4–6 feet) above the floor. For children, the breathing zone depends on height and mobility. Certain toxicants are found in highest concentration in lower breathing zones, such as heavier particles in cigarette smoke, mercury vapor from latex paint, or radon. Radon is of particular concern, because levels can accumulate substantially indoors and children are especially susceptible to the toxic effects. Exposure to radon is the second leading cause of lung cancer in the United States, associated with 15,000 to 20,000 deaths annually. The physical environment changes substantially as children reach school age and spend more time away from home. School becomes an important source of environmental toxicant exposure ( Table 1 ). The increasing incidence of childhood asthma is associated with indoor and outdoor air pollutants such as secondhand smoke and motor vehicle exhaust.
