Immune assessments in developmental and juvenile toxicology: practical considerations for the regulatory safety testing of pharmaceuticals.

The developing organism is considered to be more sensitive than the adult to immunotoxic agents. There is every reason, therefore, to include immune assessments in the regulatory testing for developmental toxicity of drugs that are intended to be used in young patients or pregnant woman. An effective strategy would be to incorporate immune assessments in the existing recommendations on pre- and post-natal toxicity study in the rat from the International Conference on Harmonisation. Immune assessments could also be included in juvenile toxicity studies to screen for effects resulting from post-natal exposure to the drug. Adequate testing methods are available to screen for developmental effects that result in immune depression. Routine immune assessments may comprise histopathological examination of the lymphoid organs/tissues and immunophenotyping of lymphocyte subsets in the blood, spleen, or thymus. These tests should be performed in rodents at various ages and at various stages of pre- and post-weaning development. Immunoglobulin and cytokine measurements, assessment of the T-cell dependent antigen response to sheep red blood cells or keyhole limpet haemocyanin antigens, and host resistance studies may be performed as apical tests at maturity. More research is required to develop methods for the detection of drugs that may render the developing organism more susceptible to hypersensitivity or autoimmunity.