Susceptibility of Children to Environmental Toxic Substances, an article by Dr. WilliamW. Au

International Journal of Hygiene and Environmental Health
Vol. 205, 1 – 3, 2002.

Susceptibility of children to environmental toxic substances

William W. Au, Ph.D.

Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, Texas 77555-1110, USA.

Abstract

Our understanding of toxicity of environmental substances is based mainly on investigations using adult human populations and matured animals.  Therefore, the scientific community and regulatory agencies have very little knowledge regarding how children respond to insult from toxic chemicals.  However, certain scientific data indicate that children are more susceptible to toxic exposure than adults because they have proportionally more intake of food contaminants, active developmental processes, multiple exposure pathways and susceptible socio-behavioral activities.  More emphasis should therefore be focused on addressing the information gap for improving the health of our children.

Introduction

Traditionally, our understanding of toxicity of environmental substances is based on human experience and from studies using experimental animals.  The knowledge is therefore generated mainly from studies involving adult human populations (workers) or matured animals. As a result, protection and regulatory standards that are developed from these data are used universally for adults and children.  However, concerns have been raised that there can be profound differences between children and adults from exposure to toxic substances.  Chemical exposures during childhood or in utero could increase health problems such as cancer during childhood or later in life (National Research Council, 1993; Quang and Woolf, 2000).  This concern is supported by the reported increases in rates of brain cancer in children and of testicular cancer in young adults (Charnley and Putzrath, 2001).  It becomes clear that the regulatory policies that are developed based on observations in adults are not adequate in protecting children.  This led to the signing of the executive order by former president Clinton, Protection of Children from Environmental Health Risk and Safety Risks (Executive Order, 1997).  In response to the Executive Order, several regulatory and public health agencies have set up specific programs to address children’s environmental health issues.

Health consequences from exposure to toxic chemicals

Numerous studies have been conducted to elucidate how toxic environmental chemicals induce cancer.   Therefore, environmental cancer will be used as a model in this commentary to provide a general explanation on the development of health problems from exposure to environmental toxicants. 

Upon exposure to a chemical carcinogen, the chemical is absorbed, distributed and metabolized in various tissues and organs in the body. From the metabolic process, metabolites are produced which may be more reactive than the original chemical or may be inactive.  Differences in an individual’s ability to metabolize chemicals contribute significantly to variations in toxicological responses to hazardous chemicals.  Many of these variations have recently been shown to be due to the inheritance of variant chemical metabolizing genes (Au et al., 2001).  The toxicological effects may range from the expression of DNA damage, chromosome aberrations, gene mutation and perturbation of cell proliferation.  These effects are known to be some of the initial events in the development of cancer (Greenblatt et al., 1994; Bonassi and Au, 2002).

Children specific activities

Children are more active than adults.   As a result, they drink more water, breathe more air and eat more food per pound of body weight compared to adults.  Therefore, they are proportionally exposed to more toxic chemicals from the environment and from materials they ingest than adults, making them susceptible to toxicants.  Furthermore, children have unique activities and behavior that may increase their susceptibility.  The hand-mouth behaviors of toddler put them at risk of ingestion of a variety of contaminated materials.  Children are less aware of standard hygiene such as the avoidance of contaminated food and their dietary preferences may cause them to consume a proportionally large amount of a particular type of food.  Children are less likely than adults in reading information labels on food products and warning labels.  Children have their own social activities.  Some activities may involve the consumption of large amount of certain dietary ingredient that can cause overt toxicity, leading to the need for emergency care.  An example is the abuse of nutmeg, an aromatic chemical, by a 13-year-old female who ended up in an emergency room in New York (Sangalli and Chiang, 2000).  Nutmeg is used as spice for food preparation and, based on conventional assessment, one would not expect the consumption of nutmeg is of health concern. 

Age as a susceptibility factor

The embryos, fetuses and children undergo tremendous developmental changes and most of these changes are absent in the adult.  These changes involve complex and integrated activities that lead to the expression of unique processes such as differentiation, organogenesis, morphogenesis, rapid and controlled cell division and developmental stage-specific gene activities.  How these developmental changes alter children’s response to toxicological insult in comparison to adult remains to be elucidated (Faustman et al., 2000).  However, in some rare occasions, the age-dependent susceptibility phenomenon has been documented.  The carcinogenic activity of diethylstilbestrol is a good example.  The standard rodent cancer bioassay would not have predicted the in utero carcinogenic effects of this chemical.  Other supportive evidence is from the cancer incidence among the Japanese atomic bomb survivors.  The incidences for leukemia and breast cancer are much higher for those who were exposed to the atomic bomb fall-out at a younger age than those at an older age (Upton, 1984).  In the methyl isocyanate accident in Bhopal, India, children are disproportionately affected, as documented in increased seizures, coma and lethality (Mehta et al., 1990).  Fetuses and children are much more sensitive to the toxicity of environmental toxicants than adults, as demonstrated in the Minamata Bay, Japan, methylmercury contamination problem (Powell, 1991; Koos and Longo, 1976).  It should also be stated that, in some cases, children are less susceptible than the adults.

Contaminants in food can be accumulated in the mother and passed on to the embryos and fetuses via the placenta.  In addition, infants are further exposed to the contaminants via the human milk.  Certain man-made chemicals that have long-half lives, e.g. polychlorinated biphenyls and organochlorine pesticides, are present in higher concentrations in milk of mothers from industrialized countries than from under-developed countries (Przyrembel et al., 2000).

Physiological differences

Besides differences from adult in the intake of chemicals, physiological differences in the absorption of chemicals via the gastrointestinal track have been documented.  For example, young children absorb approximately 50% of ingested lead compared to 10% among adults (Royce, 1992).  Detoxification of hazardous chemicals is a critical event in the defense against their toxic effects.  However, infants are deficient in such defense mechanism, as most chemical metabolizing enzyme activities evolve within a few days to weeks after birth  (Linakis, 1998).

Conclusions

The scientific community and regulatory agencies have very little knowledge regarding how children respond to insult from toxic chemicals.   However, certain scientific data indicate that children are more susceptible to toxic exposure than adults because they have proportionally more intake of food contaminants, active developmental processes, multiple exposure pathways and susceptible socio-behavioral activities.   Therefore, a national committee has previously stated that “an uncertainty factor up to ten-fold … be consider … when data from toxicity testing relative to children are incomplete.” (National Research Council, 1993; Landrigan et al., 2001).  The recommendation was adopted by the 1996 Food Quality Protection Act with respect to pesticides.  In addition, test for prenatal developmental toxicity and the 2-generation reproductive study protocol are recommended for pesticides (Kimmel and Makris, 2001).  The Executive Order in the US offers a tremendous stimulus towards a concerted effort in addressing children-specific susceptibility to environmental and ingested toxicants.  Since developing countries have significantly more children in the populations than developed countries, the consideration of children susceptibility should be a global concern.  These investigations may range from standard toxicological studies to molecular studies on genetic susceptibilities.  The investigations should target exposure from environmental contamination and exposure through the food chain.  From vigorous evaluation of the toxicology of chemicals and understanding children’s susceptibility, regulatory agencies will be able to set better guidelines for protecting children’s health. 

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