of an individual are likely to be more active and cause greater impact on the young, whereas those compounds that depend for their activity on the development of acquired characteristics—such as elevated blood pressure, atherosclerosis, and loss of renal function—will be more active in the elderly. For example, the red blood cells of older mice are more easily damaged by oxidants, possibly because of acquired changes in their cell membrane (Tyan, 1982) and impaired ability to withstand oxidant stress. Similarly, the increasing presence of chromosome aberrations in the cells of the older person, perhaps because of longer exposure to toxic substances in the environment, may contribute to the increased carcinogenic susceptibility of the elderly (Singh et al., 1986).


The metabolic rate, a measure of the total energy expenditure of an organism, increases as the size of the organism increases. However, when energy expenditure or energy intake is evaluated per unit of mass, it decreases with increasing body size. Thus, the metabolism of exogenous substances administered in terms of body size will generally be more rapid in the immature than in the mature animal. This may have important implications for toxicity of pesticides—decreasing toxicity when the parent compound is the toxic agent and increasing toxicity when a breakdown product is the toxic substance. However, there is a variety of other aspects of changes in metabolism that can also act to modify toxicity.

The infant's body surface area per unit of body mass is two to three times greater than the adult's. This relatively large surface area per unit of mass is associated with a metabolic rate that is more than twice the adult's on a weight basis but closer to the adult value when compared per unit of surface area. Because food and water intake is related to metabolic rate, the infant's consumption will be greater than the adult's on a weight basis, but total energy consumption will be more nearly comparable to the adult's if surface area is the basis of comparison. Thus, infants differ from adults, not only in specific metabolic and pharmacokinetic measures, but also in overall metabolic rate.

Because of differences in the types of food consumed by the young (see Chapter 5), the amount of a food consumed, with its related additives, preservatives, and contaminants, may be 1 order of magnitude higher or lower for children than for adults per unit of body weight. The percent absorption varies with the development of the gastrointestinal system. The volume of distribution also depends on the degree of maturity as well as on the solubility characteristics of the substance. Because of developmental changes in enzyme activity, rates of deactivation or activation are related to the stages of maturation. The number of cell membrane

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