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Immunotoxicant screening and prioritization in the 21st century
Citation:
LUEBKE, R. W. Immunotoxicant screening and prioritization in the 21st century. Presented at Society of Toxicologic Pathology 30th Annual Symposium: Toxicologic Pathology and the Immune System, Denver, CO, June 19 - 23, 2011.
Impact/Purpose:
Overview presentation on the use of alternative immunotoxicity models for screening and prioritization.
Description:
Current immunotoxicity testing guidance for drugs, high production volume chemicals and pesticides specifies the use of animal models that measure immune function or evaluation of general indicators of immune system health generated in routine toxicity testing. The assays are resource intensive and often require special training or experience to ensure reliable results. However, driven by efforts to reduce cost and testing in animals, and to increase the number of chemicals that can be screened, alternative methods have been or are being developed to detect potential immunotoxicity, including allergenicity and immunosuppression. Ideally, assays will be high throughput, to streamline screening and prioritization efforts, and will generate data that are suitable for risk assessment, to preclude animal testing. Models based on rodent ( Wagner et aI., 2006) and human (Oostingh et aI., 20008) transgenic reporter gene cell lines have been used to detect changes in expression of critical immune system genes after exposure to a variety of environmental chemicals. However, a limited number of compounds have been screened using these assays; additional testing is required to evaluate their utility to suggest potential modes of action, rather than simply flag potential immunotoxicants. Significantly more progress has been made in the use of alternative models to allergens while avoiding false positive signals from irritants (e.g., Sens-it-iv, ECVAM, Galbiati et al. 2011). Immunotoxicity data are also generated by projects (e.g., EPA's ToxCast, NIH's National Toxicology Program and Chemical Genomics Center) that focus on screening, modeling and identification of toxicity pathways. This presentation will provide an overview of current and alternative testing methods for immunotoxicity screening, hazard identification and testing prioritization. This abstract does not reflect EPA policy.