their potential to produce gross structural malformations. Rather, the focus is on processes that occur after the completion of organogenesis and continue well into the postnatal period. However, the origins of this broader concern with peri- and postnatal toxicology are inextricably rooted in experimental teratology.
Studies of the toxicity of xenobiotic compounds in children have demonstrated the potential for either acute or chronic exposure to result in serious malfunctions at a later age. This potential exists because of the developmental character of the physiologic/biochemical/molecular function of the young individual. While a biologic system is developing, a toxic event can alter one aspect of that development so that all subsequent reactions are altered or modified. For example, transient elevations of serum bilirubin during the newborn period may produce changes in the basal ganglia of the brain that may not become apparent until several years later but are then permanent in nature.
In this section, the committee discusses and summarizes the relative sensitivity of infants, children, and adults to the acute toxicity of chemicals. Acute toxicity here is defined as toxicity resulting from a single exposure to a chemical. The injury may be immediate or delayed in onset. Both lethality and target organ injury will be considered as toxic end points. A limited number of findings from studies of laboratory animals are summarized where data on humans are inadequate. Because of the meager data base on age-dependent acute toxicity of pesticides, some examples of pharmacologic effects and adverse effects of therapeutic agents in pediatric and adult populations are described. Attention is focused, in turn, on age-related differences in the lethality of pesticides and other chemicals, differential effects of cholinesterase inhibitors in immature and mature subjects, and age-related effects of toxic and pharmacologic actions of selected therapeutic agents.
Data on age-related susceptibility to the lethal effects of chemicals are largely limited to acute LD50 studies in laboratory animals. Done (1964) was one of the first investigators to compile the results of LD50s and other measures of lethality of a variety of chemicals in immature and mature animals. Immature animals were more sensitive to 34 chemicals, whereas mature animals were more sensitive to 24 compounds. Thiourea was 50 to 400 times more toxic (i.e., lethal) in adult than in infant rats. Conversely, chloramphenicol was 5 to 16 times more toxic in 1- to 3-day-old rats. Thus, Done (1964) concluded that immaturity does not necessarily entail greater sensitivity and that age-dependent toxicity is chemical dependent. Goldenthal (1971) tabulated LD50 values for newborn and neonatal animals