Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: A workshop summary |
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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 |
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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 |
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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. |
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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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