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Regul Toxicol Pharmacol. 2014 Feb;68(1):96-107. doi: 10.1016/j.yrtph.2013.11.012. Epub 2013 Nov 23.

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

Author information

1
The Dow Chemical Company, Midland, MI, United States. Electronic address: rboverhof@dow.com.
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.
7
National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, United States.
8
Battelle Memorial Institute, Columbus, OH, United States.
9
DuPont Haskell Global Centers for Health and Environmental Sciences, Newark, DE, United States.
10
Dow AgroSciences, Indianapolis, IN, United States.
11
Medicines Evaluation Board, Utrecht, The Netherlands.
12
ImmunoTox® Inc., Richmond, VA, United States.
13
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; ACSA; AFC; CP; CT; DART; DIT; ELISA; EOGRTS; EPA; EU; Environmental chemicals; European union; FDA; HESI; ICH; ILSI; Immunotoxicity; KLH; LLNA; NIEHS; NIOSH; NK; NOAEL; NRC; NTP; OECD; PND; RIVM; SRBC; STS; T-cell dependent antibody reaction; TDAR; Testing; US; United States; WoE; agricultural chemical safety assessment; allergic contact dermatitis; antibody forming cell; carbon tetrachloride; cyclophosphamide; developmental and reproductive toxicology; developmental immunotoxicity; dutch national institute of public health and the environment; environmental protection agency; enzyme linked immunosorbent assay; extended one-generation reproductive toxicity study; food and drug administration; health and environmental sciences institute; international conference on harmonization; international life sciences institute; keyhole limpet hemocyanin; local lymph node assay; national institute for occupational safety and health; national institute of environmental health sciences; national research council; national toxicology program; natural killer; no observed adverse effect level; organisation for economic cooperation and development; postnatal day; sheep red blood cells; standard toxicology studies; weight-of-evidence

PMID:
24280359
DOI:
10.1016/j.yrtph.2013.11.012
[Indexed for MEDLINE]
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