Screening of xenobiotics for direct immunotoxicity in an animal study

It has now been recognised that the immune system as a whole can be the target for xenobiotic induced toxicity. The discipline of immuntoxicology encompasses non specific direct immunotoxicity and immunostimulation, and specific responses like hypersensitivity and autoimmunity. Direct immunotoxicity can be determined in tiered studies, TIER 1 being a general toxicity study with emphasis on evaluation of organs belonging to the immune system, TIER 2 investigating the effects of xenobiotics on immune functionality in immunological challenge experiments. In the TIER 1 study, organ weights and histopathological evaluation of immune organs like spleen, thymus, lymph nodes, blood and bone marrow may detect the occurrence of direct immunotoxicity. The follow up studies in the TIER 2 phase can then determine the extent of the immunosuppression and identify which specific parts or cellular components of the immune system are involved. In view of the complexity of the immune system and the multitude of interactions within the immune system in vivo animal experiments are needed to investigate xenobiotics for their potential immunotoxicity. In vitro assays with in vivo exposed cells of the immune system may present additional information on the mechanisms involved in the observed direct immunotoxicity.