as LD50s are significantly different, the differences are usually less than 1 order of magnitude and often substantially less.

  • Data on age-dependent pharmacokinetics of pesticides are lacking for most animals, and the data base on pharmacokinetics and metabolism of drugs in immature humans is also limited. Available information reveals that some functional immaturities offset or cancel one another, whereas others tend to be additive. For example, inefficient gastrointestinal absorption of the anti-inflammatory drug indomethacin is offset by decreased biliary and renal clearance. Maturation of most biochemical and physiological processes occurs within the first 2 years; indeed, substantial changes occur within the first days and weeks of life. Compared to adults, therefore, neonates and infants can be anticipated to have the greatest differences in pharmacokinetics and susceptibility to pesticide toxicity—the youngest being the most likely to exhibit aberrant responses. Metabolic and renal clearance of many xenobiotics reaches and exceeds adult levels (when expressed on a body weight basis) during the first year. Therefore, older infants and young children may metabolize pesticides more extensively and eliminate them more rapidly than adults. This rapid elimination may confer increased resistance or susceptibility to toxicity, depending on the nature of the compound to which the individual is exposed.

  • On the basis of our understanding of mechanisms of action of toxicants in mature animals, including the human adult, it is generally possible to predict that similar mechanisms of action will occur in immature animals, including the human infant, child, or adolescent (i.e., biochemical mechanisms of toxicity are similar across age and developmental stages). For example, if a toxicant is cytotoxic (causes cell death) in the adult, it should cause cell death in the immature animal by the same mechanism. This principle suggests that mechanisms of action should also be comparable across species.

  • Studies of the toxicity of xenobiotic compounds in developing mammals—both laboratory animals and humans—demonstrate the potential for acute and chronic toxicity. Toxicity in the perinatal and pediatric periods is of special concern, since systems and structures under development at those times are important for survival over the lifetime of the mammal.

  • Studies in laboratory animals have demonstrated an age-related difference in acute toxicity; however, the direction of the difference is dependent on the chemical, and the magnitude of the effect is usually no more than 1 order of magnitude and often is considerably less. A developing

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