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Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: A workshop summary
Authors:Darrell R. Boverhof  Greg Ladics  Bob Luebke  Jane Botham  Emanuela Corsini  Ellen Evans  Dori Germolec  Michael Holsapple  Scott E Loveless  Haitian Lu  Jan Willem van der Laan  Kimber L. White Jr.  Yung Yang
Affiliation:1. The Dow Chemical Company, Midland, MI, United States;2. DuPont Pioneer, Wilmington, DE, United States;3. Cardiopulmonary and Immunotoxicology Branch, US Environmental Protection Agency, Research Triangle Park, NC, United States;4. Syngenta Ltd., Macclesfield, UK;5. Laboratory of Toxicology, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy;6. Pfizer, Inc., Groton, CT, United States;g National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, United States;h Battelle Memorial Institute, Columbus, OH, United States;i DuPont Haskell Global Centers for Health and Environmental Sciences, Newark, DE, United States;j Dow AgroSciences, Indianapolis, IN, United States;k Medicines Evaluation Board, Utrecht, The Netherlands;l ImmunoTox® Inc., Richmond, VA, United States;m Office of Pesticides Programs, US Environmental Protection Agency, Washington, DC, United States
Abstract:
As experience is gained with toxicology testing and as new assays and technologies are developed, it is critical for stakeholders to discuss opportunities to advance our overall testing strategies. To facilitate these discussions, a workshop on practices for assessing immunotoxicity for environmental chemicals was held with the goal of sharing perspectives on immunotoxicity testing strategies and experiences, developmental immunotoxicity (DIT), and integrated and alternative approaches to immunotoxicity testing. Experiences across the chemical and pharmaceutical industries suggested that standard toxicity studies, combined with triggered-based testing approaches, represent an effective and efficient approach to evaluate immunotoxic potential. Additionally, discussions on study design, critical windows, and new guideline approaches and experiences identified important factors to consider before initiating DIT evaluations including assay choice and timing and the impact of existing adult data. Participants agreed that integrating endpoints into standard repeat-dose studies should be considered for fulfilling any immunotoxicity testing requirements, while also maximizing information and reducing animal use. Participants also acknowledged that in vitro evaluation of immunosuppression is complex and may require the use of multiple assays that are still being developed. These workshop discussions should contribute to developing an effective but more resource and animal efficient approach for evaluating chemical immunotoxicity.
Keywords:2,4-D, 2,4-dichlorophenoxyacetic acid   ACD, allergic contact dermatitis   ACSA, agricultural chemical safety assessment   AFC, antibody forming cell   CP, cyclophosphamide   CT, carbon tetrachloride   DART, developmental and reproductive toxicology   DIT, developmental immunotoxicity   ELISA, enzyme linked immunosorbent assay   EOGRTS, extended one-generation reproductive toxicity study   EPA, environmental protection agency   EU, European union   FDA, food and drug administration   HESI, health and environmental sciences institute   ICH, international conference on harmonization   ILSI, international life sciences institute   KLH, keyhole limpet hemocyanin   LLNA, local lymph node assay   NK, natural killer   NIEHS, national institute of environmental health sciences   NIOSH, national institute for occupational safety and health   NOAEL, no observed adverse effect level   NRC, national research council   NTP, national toxicology program   OECD, organisation for economic cooperation and development   PND, postnatal day   RIVM, dutch national institute of public health and the environment   SRBC, sheep red blood cells   STS, standard toxicology studies   TDAR, T-cell dependent antibody reaction   US, United States   WoE, weight-of-evidence
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