NICEATM conducted a retrospective analysis to determine if acute oral toxicity data can be used reliably to assign EPA acute dermal hazard classifications, potentially reducing the number of animals needed for pesticide testing. NICEATM obtained high-quality data for 910 pesticide-active ingredients and formulations from EPA toxicity reports, peer reviewed publications, and databases. Oral hazard classifications based on rat oral LD50 values were compared to dermal hazard classifications based on rat dermal LD50 values. Results suggest that acute oral hazard categories are sufficiently protective for acute dermal hazard classification. EPA used these analyses to support guidance for waiving acute dermal toxicity tests required for pesticide formulations. The analysis was described in a poster (Paris et al.) presented at the 2016 Society of Toxicology (SOT) annual meeting, and a manuscript describing this work is in preparation.
NICEATM is supporting an NTP effort to systematically evaluate the application of zebrafish in NTP toxicology studies (SEAZIT). This effort will provide fundamental knowledge on the use of zebrafish in toxicology. In FY 2016, NICEATM and other SEAZIT team members conducted a series of interviews with researchers considered to be experts in the use of zebrafish in toxicology studies. These interviews identified areas key to development of a harmonized testing protocol for embryonic zebrafish studies and important sources of variability among laboratories. Information from these interviews and from a literature search will be compiled into a manuscript to be submitted for publication in FY 2017. NICEATM will also present a webinar series in February and March 2017 on Using Informatics to Improve Data Analysis of Chemical Screening Assays Conducted in Zebrafish. Information about the webinars is on the NTP website.
NICEATM is working with other NTP scientists at NIEHS to establish a list of developmental toxicants that cause subtle effects, as opposed to being potent or multisite teratogens. The toxicants identified will be candidates for testing with in vitro assays using primary cells, stem cells, or cell lines, as well as in vivo assays using lower order organisms such as zebrafish or Caenorhabditis elegans. Results from this testing may be compared to available in vivo mammalian data from rodents, rabbits, and humans. The toxicant list is being constructed with input from experts in industry, academia, and government, and is expected to include agrochemicals, pharmaceuticals, and other chemicals. NICEATM is also conducting a review of data from completed NTP studies and the scientific literature in support of this effort.
In June 2016, NICEATM requested available data and information on approaches and technologies currently used for identifying potential developmental toxicants. Three responses were received that described assays using stem cells or C. elegans with in vitro assays to screen for potential developmental toxicants. Submitted information is being used to assess the state of the science and determine technical needs for alternative methods to evaluate the potential of chemicals to induce adverse effects in offspring.
NICEATM is collaborating with test method developer CertiChem, Inc., to validate an in vitro test method that uses MDA-Kb2 human breast cancer cells to measure androgen receptor agonist and antagonist activity. The study will test 67 reference chemicals to characterize the reliability and relevance of the method, and 30 consumer products to evaluate the utility of the method beyond single chemicals. The study is planned to run through summer 2017.
NICEATM collaborated with ICCVAM scientists to develop integrated testing strategies that use non-animal data to predict skin sensitization hazard. Three manuscripts published or accepted for publication in FY 2016 describe strategies to use non-animal data to predict outcomes of animal skin sensitization tests, human skin sensitization tests, and human or animal tests for skin sensitization potency classification.
NICEATM collaborated with scientists at the University of North Carolina at Chapel Hill to develop quantitative structure-activity relationship (QSAR) models to support identification of potential human skin sensitizers without using animals. A manuscript submitted for publication in FY 2017 describes QSAR models that predict human skin sensitization test results.
NICEATM collaborated with the Cosmetics Europe Skin Tolerance Task Force to evaluate the integrated approaches to testing and assessment of skin sensitization that have been submitted to the Economic Co-operation and Development. NICEATM has evaluated six IATAs against a set of previously untested chemicals with in vitro and in silico data provided by Cosmetics Europe. Manuscripts describing the datasets and the outcome of the IATA analyses are in preparation.
Optisafe is an in vitro test method that assesses the potential to cause eye irritation by measuring the damage induced by application of a test substance to a semipermeable membrane. NICEATM is coordinating an ICCVAM-sponsored multi-laboratory validation study to determine the reliability and relevance of the OptiSafe test method. Training of participating laboratories is underway with the first phase of chemical testing to begin in FY 2017.
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