Georgia Poison Center, Emory University School of Medicine, Atlanta, Georgia Cynthia F. Bearer, M.D., Ph.D.

Case Western Reserve University, Rainbow Babies and Children’s Hospital, Cleveland, Ohio David Bellinger, Ph.D., M.Sc.

Harvard Medical School, Neuroepidemiology Unit, Children’s Hospital, Boston, Massachusetts Gershon H. Bergeisen, M.D., M.P.H.

U.S. Environmental Protection Agency, Office of Emergency and Remedial Response, Washington, D.C.

Joy E. Carlson, M.P.H.

Children’s Environmental Health Network, Emeryville, California Joan M. Cranmer, Ph.D.

University of Arkansas for Medical Sciences, Arkansas Children’s Hospital, Little Rock, Arkansas Carole A. Kimmel, Ph.D.

U.S. Food and Drug Administration, and the U.S. Environmental Protection Agency, National Center for Environmental Assessment, Washington, D.C. Philip J. Landrigan, M.D., M.Sc.

Mount Sinai School of Medicine, New York, New York Susanne T. White-Sims, M.D., M.P.H.

Louisiana State University Medical Center, New Orleans, Louisiana

ATSDR STAFF

Barry L. Johnson, Ph.D., Assistant Surgeon General, Assistant Administrator

Robert W. Amler, M.D., M.S., Chief Medical Officer

Patricia H. Price, D.O., Medical Officer

Developing human beings in the womb and through puberty can be uniquely vulnerable to environmental toxicants, depending on the substance and the exposure situation. There are several reasons for this different susceptibility.

Before birth, children are forming the body organs that need to last a lifetime (Landrigan and Carlson 1995). This is the time when chemical injury leads to its greatest effects. Injury during this period of growth may lead to malformation (teratogenesis) of organs and disruption of function, and premature death. Exposure occurs via the placenta; exposure of the mother usually leads to exposure of the child.

After birth, children may have greater exposures to environmental toxicants than adults. Pound for pound of body weight, children drink more water, eat more food, and breathe more air than adults. For example, children in the first 6 months of life drink 7 times as much water per pound as average American adults. Children 1 through 5 years of age eat 3 to 4 (or more) times as much food per pound body weight as average American adults. The air intake of a resting infant is twice that of an adult. Two characteristics of children further magnify their exposures to toxicants in the environment: (1) their typical hand-to-mouth behavior, which increases their ingestion of any toxicants in dust or soil, and (2) their play activities close to the ground, which increase their exposure to toxicants in dust and soil as well as to any toxicants that form low-lying layers in the air, such as certain pesticide vapors. The obvious implication for environmental health is that children will have substantially greater exposures than adults to any toxicants that are present in water, food, or air. This fact has been demonstrated very clearly in the case of children’s exposures to pesticides in the diet.

Other exposure pathways, while not unique to childhood, may affect the child unexpectedly and excessively. For example, children may be exposed to hazardous materials from workplaces by the unknowing or unwise transfer of workplace materials to the home (NIOSH 1995a). In addition, child labor restrictions typically address safety hazards but not hazards posed by toxic substances. Children’s main occupation is attending school, and school buildings may pose toxic hazards by virtue of location or construction. Children’s metabolic pathways, especially before birth and in the first months after birth, are immature compared to those of adults. The ability of children to metabolize and excrete certain toxicants is different from that of adults. In some instances, children are actually better able than adults to detoxify environmental toxicants. More typically, however, they are less well able than adults to detoxify chemicals and thus are more vulnerable to them. Children are undergoing rapid growth and development, and their developmental processes may be easily disrupted (Landrigan and Carlson 1995). Many organ systems in young children, the nervous system and the lungs in particular, are undergoing very rapid growth and development in the first months and years of life. Structures are being developed and vital connections established. Indeed, development of the nervous system continues all through childhood. Neither the nervous system nor the lungs are well able to repair any structural damage that is caused by environmental toxicants. Thus, if cells in the developing brain are destroyed by chemicals such as lead, mercury, or solvents, or if the formation of vital connections between cells is blocked, there is a high risk that the resulting neurobehavioral dysfunction will be permanent and irreversible. The endocrine system that regulates many functions in the body including growth, sexual maturation, and homeostasis, may be an important target for toxicants. Adolescents often enter the workforce at the lowest levels, where chemical exposures are probable (American Academy of Pediatrics 1995; NIOSH 1994, 1995b, 1996). Long-term studies of this population are notably lacking. The immune system can have long-lasting alterations after perinatal exposure to environmental toxicants. Besides changing the response to infection, such alterations can also affect the regulation of the development of other systems such as the nervous and reproductive systems (Birnbaum 1995). Because most children have more future years of life than adults, they have more time to develop chronic diseases triggered by early environmental exposures. Many diseases that are triggered by toxicants in the environment develop decades after the exposure. Examples include lung cancer and malignant mesothelioma caused by exposure to asbestos; leukemia caused by benzene; breast cancer that might be caused by DDT; cardiovascular disease and diabetes related to nutritional alterations; and certain chronic neurologic diseases, such as dementia and Parkinson’s disease, that might be caused by exposures to environmental neurotoxicants. Many of those diseases are now thought to be the products of multistage processes within the body’s cells that require many years to progress from earliest initiation to actual manifestation of illness. Consequently, certain carcinogenic and toxic exposures sustained early in life appear more likely to lead to disease than the same exposures encountered later in life.

In addition to the thousands of chemicals already in use, hundreds of new chemicals are developed every year and released into the environment. Thus, the extent of children’s exposure to synthetic chemicals will almost certainly continue to increase. The toxic effects of most of these chemicals on children, particularly long-term effects, are largely unknown. The problem is not going away. The challenge, therefore, is to understand the unique risks to children from environmental toxicants acting singly or in combination. Only with this knowledge can our society ensure children that they can grow, develop, and reach maturity without excess risk of birth defects, neurologic impairment, developmental disabilities, immune dysfunction, reproductive damage, cancer, or premature death being associated with their environmental exposures. All children are completely dependent on adults for housing decisions, access to medical care, education, and most risk management decisions. Adults, and the institutions they create, have an obligation to make ethical, responsible, and forward-thinking decisions on behalf of the children of today and tomorrow.

Environmental toxicants are a persistent, growing cause of preventable illness in children. Knowledge about this group of illnesses is also growing (Goldman 1995). That we must anticipate the occurrence of these illnesses is a challenge; that we can prevent or mitigate these illnesses makes such actions an imperative. ATSDR has asked the workgroup for guidance in focusing its actions. Some compelling problems are listed here as examples of these challenges; there are other important topics not listed here, such as environmental tobacco smoke and asbestos.

Benzene

Benzene exposure causes acute myelogenous leukemia. The dose and duration of exposure needed to cause this cancer is unknown. However, exposure beginning in childhood results in longer times to be exposed and a longer time to develop the cancer. This is an example of an exposure with latent effects, that is, exposure in childhood may lead to the development of disease in adult life.

Lead

According to the Centers for Disease Control and Prevention (CDC), 930,000 children in the United States in 1990 had whole blood lead levels over 10 æg/dL (CDC 1997), which are levels that put their intellectual development at risk. Lead exposure during childhood has recently been linked with adolescent aggressive behavior problems (Needleman 1996). After the public health success of removing lead from gasoline, house paint, and food cans, the main exposure now comes from existing paint in older houses. Lead exposure of children also continues from industrial facilities, via the effluent from plants or the clothes of workers.

Mercury

Pollution with metallic mercury leads to the production of methylmercury in the environment. Methylmercury may bioaccumulate in the food chain. Ingestion of contaminated fish by pregnant women may led to cerebral palsy and severe mental retardation, as occurred in Minimata, Japan. Other prenatal exposures have led to neurodevelopmental delays and seizures (Koos and Longo 1976; Amler et al. 1996a).

Nitrates and Nitrites

These agricultural chemicals continue to cause contamination of water supplies (Johnson and Kross 1990). Nitrites will cause methemoglobinemia when the amount ingested exceeds the individual’s detoxification capacity. Children not only drink more per pound body weight but, particularly in the first year of life, also have a limited capacity for detoxification. All standards for assessment of these chemicals must be made on the basis of data for the infant and child.

Pesticides

Children can be exposed to pesticides by direct contact, by inhalation, and through their food, including breast milk. The National Research Council estimates that 50% of all the pesticides a person ingests in a lifetime is ingested in the first five years of life (NRC 1993). Some foods contain enough pesticides that, if prepared for children, they can contain a nearly toxic dose. Several pesticides are hormone disruptors in animals. The long-term effects of pesticides on the development of children and adolescents have not been studied adequately.

Polychlorinated Biphenyls (PCBs)

In the Great Lakes region of the United States, children are exposed to polychlorinated biphenyls (PCBs) in utero and during childhood, by the ingestion of sport fish (ATSDR 1990, 1994a). Several studies have shown that children exposed to PCBs and other contaminants have lower IQs than children not eating fish caught in the region (Jacobson and Jacobson 1996). Trichloroethylene (TCE)

Early exposure to trichloroethylene (TCE) is associated with reports of hearing loss and delays in speech development (ATSDR 1995a; Burg et al. 1995).

Triggers of Asthma

The doubling of the death rate from asthma in U.S. children since 1980 has been documented by the CDC (1996a). Environmental pollutants are major contributors to asthma, the most common admission diagnosis in many children’s hospitals. The impact of these trends on health and health care resources is great. Asthma is caused or triggered by environmental tobacco smoke, ozone from smog, and particulates in the air. Cockroaches, house-dust mites, pollens, and molds are major asthma-triggering antigens affecting the pediatric population.

ATSDR’s mission is to prevent exposure and adverse human health effects and diminished quality of life associated with exposure to hazardous substances from waste sites, unplanned releases, and other sources of pollution present in the environment (ATSDR 1996a). ATSDR divides its activities between those that relate to a particular site and those that relate to a specific hazardous substance. Site-specific activities include public health assessments at hazardous waste sites, and health studies and exposure investigations in communities located near such sites.

Hazardous Waste Sites

Uncontrolled hazardous waste sites are prevalent throughout the United States. The U.S. Environmental Protection Agency (EPA), in 1996, listed approximately 15,000 sites in the United States; 1,371 were proposed or listed on the National Priorities List (NPL) on the basis of a hazard ranking system. Each of the 50 states has at least 1 NPL site; 5 states (California, Michigan, New Jersey, New York, and Pennsylvania) contain 37% of all the sites and 30% of the children ó17 years of age in the United States. Approximately 11 million people, of whom 25% to 35% are children ó17 years, live within 1 mile of an NPL site (ATSDR 1996b). African Americans, Native Americans, and people of Hispanic origins comprise a greater proportion of these communities than those outside the waste site areas (Heitgerd et al. 1995). The potential adverse human health impact of hazardous waste sites is a considerable source of concern to the general public as well as health professionals and government agencies.

The majority (65% 70%) of uncontrolled hazardous waste sites in the United States are waste storage/treatment facilities (including landfills) or former industrial properties (ATSDR 1996b). Many of these properties have been abandoned, and most have more than one major chemical contaminant. Less common are waste recycling facilities and mining sites, which may be active, inactive, or abandoned. Another group of hazardous waste sites is associated with federal government facilities, such as military facilities and nuclear energy complexes. The National Research Council has cited 17,482 contaminated sites at 1,855 military installations and 3,700 sites at 500 nuclear facilities. Some of these sites cover large geographic areas and are contaminated with very complex mixtures of wastes. The substances most commonly released into environmental media (for example, air or groundwater) from uncontrolled hazardous waste sites are heavy metals and organic solvents: lead (59% of sites), trichloroethylene (53%), chromium (47%), benzene (46%), and arsenic (45%) . When EPA places a site on the NPL, the Comprehensive Environmental Response, Compensation, and Liability Act, (commonly called the Superfund Act, passed in 1980 and amended in 1986) provides monies for remediation (cleanup) of the site and an array of public health actions in nearby communities (Johnson 1995). ATSDR conducts public health assessments to evaluate the potential health hazards faced by communities in proximity to every proposed, listed, or former NPL site. In many cases this work is conducted by state health departments under ATSDR sponsorship and review. A site is assigned a hazard category according the human health hazard it poses, on the basis of professional judgement and weight-of-evidence criteria. In the 3-year period 1993 1995, this process identified a health hazard at 49% of sites and an urgent hazard at 4%of sites (ATSDR 1996b). It is important to note that a site-specific epidemiologic or other investigation is needed to establish the actual hazard to health. Of the public health assessments conducted to date at 1,371 sites, about 60% have included recommendations that address the need for intervention to interrupt ongoing exposure pathways. These interventions have included provision of alternative drinking water, issuance of fish consumption advisories, posting of warning notices, restrictions of site access, and (rarely) relocation of community residents.