the central nervous system, could permanently prevent normal physical maturation. Also of concern are the physical properties of the toxic substances. For example, water-soluble compounds will be more diluted when the proportion of water in the body is higher, as in infancy, and lipid-soluble substances will be more concentrated in fatty or adipose tissue when the proportion of fat in the body is lower, as may also occur in infancy.
Functional development involves changes in the operational reactions that constitute the process of living, such as the ability to digest and absorb substances in the gastrointestinal tract, to alter their composition in the liver, to develop new metabolic pathways, and to excrete chemicals in the urine. These functions also develop at differing rates, so the organism may respond to chemicals in different ways at different ages. For example, because the filtering function of the kidney develops at a rate different from that of the reabsorptive and secretory functions, the kidney's overall ability to rid the body of toxic substances and the relative ability to excrete substances that are partially reabsorbed or are secreted will vary in a nonlinear fashion with increasing age.
The development of the functions of digestion, absorption, distribution, metabolic alteration, and elimination is of major importance in studies of developmental toxicology. This importance results in part from the possibility that toxicity to a functional system (e.g., glucose homeostasis) prior to its full development may permanently affect that system, resulting in altered function (e.g., glucose metabolism) in the mature animal, and in part from differences in the rates of absorption, metabolism, and excretion and therefore differences in susceptibility to toxicity at different ages prior to maturation.
Behavioral development includes the maturational changes in physical and mental activities associated with the relation of the individual to the environment. Behavioral development has four interrelated aspects: (a) gross motor and fine motor activities; (b) cognitive ability; (c) emotional development; and (d) social development. Alteration in one of these domains can affect the development of each of the other three.
Because of the dependence of behavioral development on physical and functional development, toxic effects occurring before maturation may permanently alter behavioral development. The most commonly encountered and well-known toxicants that can permanently change all four of the components of behavioral development are bilirubin toxicity in the newborn and lead toxicity in the infant or young child. All four aspects of behavioral development are important in studies of developmental toxicology, but much more attention has been given to the first two because they are easier to measure.
The committee's conclusions regarding how infants and children differ