water, the lean body mass of the full-term infant is 82% water, compared with 72% water in the lean (fat-free or non-fat-containing) body mass of the adult. Most of the "excess" water in the infant is extracellular (Forbes, 1968). Thus, the overall amount of organ tissue per unit of whole body mass is less in the infant. One exception is the liver, which in the child is relatively larger per unit of body weight than in the adult. Several investigators have postulated that this relatively larger size of the liver could play a role in the capacity of the young child to metabolize drugs such as phenylbutazone and antipyrine more rapidly than the adult (Coppoletta and Wolbach, 1933; Alvares et al., 1975; Vesell, 1982). In addition, the organs themselves contain more water than do the organs of adults (Dickerson and Widdowson, 1960; Widdowson and Dickerson, 1960, 1964; Dickerson, 1962). Brain water decreases from 90% in the infant to 77% in the adult (Altman and Dittmer, 1973). Liver water decreases from 78% to 71% and kidney water from 84% to 81% (Widdowson, 1968). Although the total water content of skeletal muscle is relatively unchanged, the extracellular water of muscle decreases from 35% to 18%, but the intracellular water increases from 45% to 61%. The change in intracellular water is to a large extent related to an increase in cell size.

The changes in body water compartment sizes with increasing age may bear some relationship to changes in pesticide toxicity, depending on the distribution of the toxic compound. Those agents that are water soluble and distributed extracellularly will be more diluted in the youngest animals, or in human infants and small children, for comparable exposures on a milligram-per-kilogram basis. Thus one might expect toxicity to vary with age for water-soluble compounds. If the compound or its toxic metabolite is distributed intracellularly, the relatively decreased volume of intracellular water in the young would lead to toxicity varying indirectly with age. These age-related differences in toxicity emphasize the importance of ascertaining the distribution of water-soluble toxic materials within the specific tissue water compartments, extracellular or intracellular.

Cell size in infancy is relatively small. Thus, there is proportionately more cell membrane per unit of cell mass in the infant than in the adult (Cheek, 1968b). The effect of the relatively greater cell membrane and, therefore, of cell surface area compared to cell mass in the infant and young child has not been explored, but one might postulate that these proportions could increase the sensitivity of the cells of the young to compounds that act primarily at the level of the cell membrane.

DEVELOPMENT

Development, as used in this context, refers to the functional maturation of various cells, tissues, organs, organ systems, and the organism as a



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