ABSTRACT
Introduction and Defi nitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347 Historical Perspective on DIT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 Approaches to DIT Testing Framework . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351 Regulatory Perspective on DIT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355 Data Gaps and Future Directions for Assessing DIT . . . . . . . . . . . . . . . . . . . . . . . 358 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
A basic tenet associated with most protocols devoted to an assessment of developmental toxicology is that children differ signifi cantly from adults in their biological and/or physiological responses to environmental exposures or stressors.1 In the context of immunocompetence, it is known that common infectious diseases occur more often, and are usually more severe in the very young when compared to adults. In most cases, initial contacts with the infectious agent will lead to immunity, and consequently, encounters with the same agent later in life will lead to less severe reactions. In some cases, agerelated physical or physiological differences in tissues or organs are responsible for the increased susceptibility to infections. In addition, increased susceptibility can be due to the relative immaturity of the immune system in the very young that prevents the host from making an adequate response to microorganisms. Neonates are particularly susceptible to infectious agents that require adult-like production of antibodies and complement to mediate phagocytosis and bacteria killing. For children that survive with primary immunodefi ciency diseases (i.e., primarily those with defi ciencies only in
antibody production), there are increases in the frequency and severity of infections to both common and opportunistic infections. Children with less severe immunodefi ciency usually have a higher incidence and severity of infections from common pathogens, such as upper respiratory infections or repeated inner ear infections, than the general age-matched population.
