Approaches to the identification and recording of findings in the lymphoreticular organs indicative for immunotoxicity in regulatory type toxicity studies

Abstract

Recent validation studies showed that histopathological examination of the hematopoietic and lymphoreticular system is one of the most sensitive tools in the evaluation of non-specific immune stimulatory or immune suppressive effects and hazard identification of potential immunotoxicity in routine safety tests. Most immunotoxic effects have a classical dose-response relationship and an immediate effect (i.e. do not need an induction phase). The findings associated with a specific immunomodulatory response are generally not detected morphologically in routine sections of the immune system in safety studies, but may be detected, because of their effects on other organs such as skin (contact dermatitis) or joints and kidneys (immune complex deposits). Careful detailed examination of the immune system may give valuable clues for the possible mechanism of action of the test material, as was also demonstrated in these validation studies.