receptors and the degree of protein binding are similarly variable with age. Rates of excretion by the liver and kidneys depend on both the overall organ development and the differential rates of maturation of specific organ components. For example, the development of the filtration function of the kidney is slower than the development of the reabsorption and secretory functions. Finally, the cellular response itself is dependent on intracellular maturation and differentiation. Thus, the human infant or infant animal may respond quite differently from the adult of its species to many xenobiotic substances. There is no reason to believe that these differences in response would not be equally applicable to pesticides.

Developmental Toxicity Studies

Because so many bodily functions are at various stages of development throughout infancy and early childhood, toxic effects of chemical agents during these age periods not only produce the same sorts of direct injuries to established organ tissues and functions seen in adults, but also have the potential to affect the later development of anatomic, physiologic, and metabolic processes.

During organogenesis, functional integrity does not necessarily coincide with morphological maturity, and relative organ size varies as development proceeds. Because of the evolving development of various organs and tissues, the effect of exposure to toxic substances will vary in a complex way with the age at exposure. Substances that are toxic to adults may have minimal effects at one stage of development, but at another stage these same substances may produce permanent damage to the organism or may be lethal. Such effects are particularly prominent for the central nervous system. For example, radiation treatment for medulloblastoma resulted in major cognitive problems at a later age for children less than 4 years old at the time of radiation, minimal problems later if treatment occurred at 5 to 7 years of age, and no residual cognitive difficulties when radiation was administered at 8 years and older (Chin and Maruyama, 1984).

The infant kidney is immature at birth, and the relatively poor glomerular filtration rate leads to delayed drug excretion and, therefore, an increased likelihood of toxicity (Kleinman, 1982). In the liver, the capacity to detoxify drugs by the process of conjugation develops slowly and is a major factor contributing to the toxicity of chloramphenicol in infants (Vesell, 1982).

The complexity of age-related effects of exposure for a specific tissue was demonstrated by Fleisch (1980), who identified the following factors that could change with age and thus alter the age-related sensitivity of blood vessels to various drugs:

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