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Histopathologic Approaches to Detect Changes Indicative of Immunotoxicity
C. Frieke Kuper
TNO Toxicology Division, 3700 AJ Zeist, The Netherlands
Johannes H. Harleman
Novartis Pharma AG, CH 4002 Basel, Switzerland
Hans B. Richter-Reichelm
Federal Institute for Health Protection of Consumers and Veterinary Medicine, D-14196 Berlin, Germany
Joseph G. Vos
National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands, Faculty of Veterinary Medicine, 3508 TD Utrecht, The Netherlands
Toxicologic pathology is crucial in the identification and characterization of health effects following exposure to xenobiotics, mainly in toxicity experiments in rodents. Regarding regulatory toxicology, histopathology of lymphoid organs and tissues is a cornerstone in the identification of immunotoxic compounds. A 2-tier testing system is usually employed in which the first tier is a general screen for (immuno)toxicity and the second tier consists of specific immune function studies, including host resistance tests or mechanistic studies. The role attributed to histopathology of lymphoid organs in the updated Organisation for Economic Cooperation and Development and Food and Drug Administration guidelines requires improvement and standardization of the histopathology procedures. Optimalization and standardization was started in an international collaborative immunotoxicity study (ICICIS). However, several problems were left unaddressed, mostly because of the few compounds tested in this study. Based on the results of the ICICIS study and the morphologic changes induced by immunotoxic/immunomodulatory compounds observed in other investigations, suggestions are given to further improve the identification and (semi)quantification of histopathologic changes in lymphoid organs and tissues.
Key Words: Lymphoid organs • thymus • spleen • lymph node • mucosa-associated lymphoid tissue (MALT) • morphology • immunosuppression • immunomodulation
Toxicologic Pathology, Vol. 28, No. 3,
454-466 (2000)
DOI: 10.1177/019262330002800317
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