Histopathologic approaches to detect changes indicative of immunotoxicity

Toxicologic pathology is crucial in the identification and characterization of health effects following exposure to xenobiotics, mainly in toxicity ex periments in rodents. Regarding regulatory toxicology, histopathology of ly mphoid organs and tissues is a cornerstone in the identification of immunot oxic compounds. A 2-tier testing system ii usually employed in which the fi rst tier is a general screen for (immuno)toxicity and the second tier consi sts of specific immune function studies, including host resistance tests: o r mechanistic studies. The role attributed to histopathology of lymphoid or gans in the updated Organisation for Economic Cooperation and Development a nd Food and Drug Administration guidelines requires improvement and standar dization of the histopathology procedures. Optimalization and standardizati on was started in an international collaborative immunotoxicity study (ICIC IS). However, several problems were left unaddressed, mostly because of the few compounds tested in this study. Based on the results of the ICICIS stu dy and the morphologic changes induced by immunotoxic/immunomodulatory comp ounds observed in other investigations, suggestions are given to further im prove the identification and (semi)quantification of histopathologic change s in lymphoid organs and tissues.