NICEATM is conducting 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 will use these analyses to support guidance for waiving acute dermal toxicity tests currently required for pesticide formulations. The analysis is described in an abstract submitted to the 2016 Society of Toxicology (SOT) Annual Meeting.
NICEATM staff collaborated with scientists at the Procter and Gamble Company to develop an approach for identifying potential skin sensitizers and characterizing skin sensitization potency without conducting animal tests. The collaboration produced a widely available, open source version of a previously published integrated testing strategy. Revisions of the original strategy improved overall accuracy of the approach and enabled consideration of the variability in reference data. A poster describing improvements to the strategy was presented at the 2015 Society of Toxicology annual meeting. Other improvements to simplify model inputs and refine potency estimates are described in a submitted manuscript.
NICEATM is collaborating with scientists at the University of North Carolina at Chapel Hill to develop QSAR models to support identification of potential human skin sensitizers without using animals. Two papers published in FY 2015 described QSAR models developed for skin penetration and to predict results for animal tests to identify sensitizers. More recent efforts have focused on developing QSAR models to predict human skin sensitization. A manuscript describing these models is in preparation.
NICEATM staff used structure-activity relationship methods to predict toxicity of chemicals that spilled into the Elk River in West Virginia in January 2014. These studies of 4-methylcyclohexanemethanol, the major component of the spill, might cause skin or eye irritation or affect development of offspring of pregnant subjects. These results were used to help select subsequent toxicology studies. A summary of activities carried out to determine toxicity of chemicals involved in the Elk River spill is available on the NTP website.
NICEATM is collaborating with the test method developer CertiChem Inc. on evaluation of an MDA-Kb2 androgen receptor activity assay. This medium-throughput in vitro test measures androgen receptor agonist and antagonist activity. This project is a proof-of-concept evaluation of the method for a blinded set of chemicals. Testing began in September 2015, and was completed in October 2015. Data analysis will be conducted in FY 2016.
NICEATM is part of 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.
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 in 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 (C. 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 from industry, academia, and government, and is expected to include agrochemicals, pharmaceuticals, and other chemicals.
NICEATM is participating on the Acute Toxicity Working Team of the European Partnership for Alternative Approaches to Animal Testing. This team is investigating methods that could circumvent the need for in vivo acute lethality testing when determining acute classification and labeling of new agrochemical and biocide active substances, and industrial chemicals.
NICEATM is collaborating with the Cosmetics Europe Skin Tolerance Task Force to evaluate the integrated approaches to testing and assessment (IATA) of skin sensitization that have been submitted to the Economic Co-operation and Development (OECD). NICEATM has evaluated seven IATAs against a naïve set of 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.
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