TOXCAST AND THE USE OF HUMAN RELEVANT IN VITRO EXPOSURES: INCORPORATING HIGH-THROUGHPUT EXPOSURE AND TOXICITY TESTING DATA FOR 21ST CENTURY RISK ASSESSMENTS (BRITISH TOXICOLOGICAL SOCIETY ANNUAL CONGRESS)

The path for incorporating new approach methods and technologies into quantitative chemical risk assessment poses a diverse set of scientific challenges. These challenges include sufficient coverage of toxicological mechanisms to meaningfully interpret negative test results, development of increasingly relevant test systems, computational modeling to integrate experimental data, putting results in a dose and exposure context, characterizing uncertainty, and efficient validation of the test systems and computational models. The presentation will cover progress at the U.S. EPA in systematically addressing each of these challenges and delivering more human-relevant risk-based assessments. This abstract does not necessarily reflect U.S. EPA policy.

Performance and Durability of Environmental Barrier Coatings on SiC/SiC Ceramic Matrix Composites

Abstract: This presentation highlights advanced environmental barrier coating (EBC) and SiC-SiC Ceramic Matrix Composites (CMC) systems for next generation turbine engines. The emphasis will be placed on fundamental coating and CMC property evaluations; and the integrated system performance and degradation mechanisms in simulated laboratory turbine engine testing environments. Long term durability tests in laser rig simulated high heat flux the rmomechanical creep and fatigue loading conditions will al…

US EPA – A*STAR PARTNERSHIP – ACCELERATING THE ACCEPTANCE OF NEXT-GENERATION SCIENCES AND THEIR APPLICATION TO REGULATORY RISK ASSESSMENT (A*STAR SYMPOSIUM, SINGAPORE)

The path for incorporating new alternative methods and technologies into quantitative chemical risk assessment poses a diverse set of scientific challenges. Some of these challenges include development of relevant and predictive test systems and computational models to integrate and extrapolate experimental data, and rapid characterization and acceptance of these systems and models. The series of presentations will highlight a collaborative effort between the U.S. Environmental Protection Agency (EPA) and the Agency for Science, Technology and Research (A*STAR) that is focused on developing and applying experimental and computational models for predicting chemical-induced liver and kidney toxicity, brain angiogenesis, and blood-brain-barrier formation. In addressing some of these challenges, the U.S. EPA and A*STAR collaboration will provide a glimpse of what chemical risk assessments could look like in the 21st century.

Microbial Standards of Commercially Available Produce

Abstract: Limits and guidelines are set on microbial counts in produce to protect the consumer. Different agencies make specifications, which constitute when a product becomes unsafe for human consumption. Producers design their procedures to comply with the limits, but they are responsible creating their own internal standards. The limits and guidelines are summarized here to be applied to assess the microbial safety of the NASA Veggie Program.

TOXCAST PROFILING IN A HUMAN STEM CELL ASSAY FOR DEVELOPMENTAL TOXICITY (SOT)

We correlated the ToxCast library in a metabolic biomarker-based in vitro assay (Stemina devTOXqP) utilizing human embryonic stem (hES) cells (H9 line). This assay identifies the concentration of a chemical that disrupts cellular metabolism in a manner indicative of teratogenicity [Palmer et al. 2013]. Undifferentiated H9 cells were exposed for 72h and media from the final 24h period was analyzed by LC-MS to determine the ornithine to cystine ratio (ORN/CYSS). ORN is derived from arginine breakdown during the citric acid cycle and CYSS is formed by oxidation of cysteine molecules that covalently link via a disulfide bond, and the corresponding ‘teratogen index’ based on ORN/CYSS falling below 0.88. To date, the raw and plate-normalized data for 286 samples in concentration series (269 chemicals plus replicates, n=3) and another 812 samples at a single concentration (n=4) have been entered into the ToxCast pipeline for QA, processing, analysis and eventual release to the public. A preliminary analysis revealed the following trends. First, 166 compounds (15.5% of the tested compounds) were ‘active’ based on the default ORN/CYSS threshold (0.88). These included many known teratogens, such as trans-retinoic acid (LEC = 3 nM), 5-fluorouracil (100 nM), methotrexate (100 nM), thalidomide (300 nM), and carbamazepine (3 uM) among others. Second, for 23 compounds with FDA codes (A,B,C,D,X) or ECVAM classifiers, the default model had a balanced accuracy of 84% (sensitivity 0.80, specificity 0.88). Third, Many chemicals not yet classified were predicted positive, including the angiogenesis inhibitors TNP-470 (10 nM) and 5HPP-33 (10 uM). Fourth, at the concentrations tested specificity was demonstrated for a parent-metabolite pair where only the proximate teratogen was active; for chemical stereoisomer pairs where only one compound was active; and for 3 closely-related structural isomers where only one structure was active. Cross-referencing with ToxCastDB (in vitro) and ToxRefDB (in vivo) is being undertaken to assess the added value of the devTOXqP assay performance in computational models built for predictive teratogenicity in a human cell-based system. (Disclaimer: this abstract does not reflect EPA policy).

Urban Biomining Meets Printable Electronics: End-To-End at Destination Biological Recycling and Reprinting

Abstract: Space missions rely utterly on metallic components, from the spacecraft to electronics. Yet, metals add mass, and electronics have the additional problem of a limited lifespan. Thus, current mission architectures must compensate for replacement. In space, spent electronics are discarded; on earth, there is some recycling but current processes are toxic and environmentally hazardous. Imagine instead an end-to-end recycling of spent electronics at low mass, low cost, room temperature, and in a …

Dynamic Technical Formulations, LLC. Issues a Voluntary Nationwide Recall of Tri-Ton Due to the Presence of Andarine and Ostarine

Roswell, GA – Dynamic Technical Formulations LLC. is voluntarily recalling all lots of Tri-Ton. This product was sold in 90 count bottles as a dietary supplement and includes all lot number and expiration dates of the product. The US Food and Drug Administration (FDA) lab analysis of Tri-Ton was found to contain andarine and ostarine which are selective androgen receptor modulators (SARMs) that are considered unapproved drugs and anabolic steroid-like substances.

TOXCAST CHEMICAL AND BIOACTIVITY PROFILES FOR IN VITRO TARGETS IN THE RETINOID SIGNALING SYSTEM (SOT)

A predictive model for prenatal developmental toxicity using ToxCast Phase I showed the RAR assay set to be the strongest weighting factor (Sipes et al. 2011). Retinoid signaling mediates growth and differentiation of the embryo. ToxCast has 6 reporter assays for trans-activation of retinoic acid receptors (RARa, RARb, RARg, and RXRa, RXRb, RXRg) and cis-activation of DR5 response elements by RAR/RXR, yielding a total of 879 ToxCast AC50s (conc. 50% effect) mapped to molecular targets in the retinoid system. In total, 97 of 1858 chemicals (5.2%) hit ≥one assays in the retinoid system at an AC50 below 2 uM. Several persistent organochlorines activated the RAR system at AC50s below 2 uM; several organotins and tert-butyl compounds activated the RXR system below 0.2 uM and 2 uM, respectively. All-trans retinoic acid was the most potent chemical tested in the RARa (AC50 = 0.43 nM) and RXRa (AC50 = 0.31 nM) trans-activation assays, and closely followed several tributyltin compounds as the most potent on the DR5 (AC50 = 6.26 nM) assay. A subset of 263 chemicals was tested on mouse embryonic stem cell (mESC) differentiation and cytotoxicity. In all 54% of the subset showed effects on mESC, including 58% of the DR5 compounds, 63% of hCYP1A1 compounds and 81% of RAR/RXR compounds. A preliminary analysis with the devTOXquickPredict (Stemina) ESC assay revealed a weak correlation with chemicals active on the RAR/RXR/DR5 system and a targeted biomarker response (ORN/CYSS ratio) that is ~84% predictive for teratogenicity in a human system. In conclusion, in vitro profiling of retinoid signaling identified ~ 5% of ToxCast chemicals with a potential for disruption of retinoic acid signaling through trans-activation of RAR or RXR at submicromolar concentrations. The potential for RAR and RXR to heterodimerize with different nuclear receptor families suggests these compounds may potentially disrupt multiple signaling pathways. This abstract does not reflect EPA policy.

Digital Device Architecture and the Safe Use of Flash Devices in Munitions

Abstract: Flash technology is being utilized in fuzed munition applications and, based on the development of digital logic devices in the commercial world, usage of flash technology will increase. Digital devices of interest to designers include flash-based microcontrollers and field programmable gate arrays (FPGAs). Almost a decade ago, a study was undertaken to determine if flash-based microcontrollers could be safely used in fuzes and, if so, how should such devices be applied. The results were docu…

Free-Space Quantum Key Distribution with a High Generation Rate KTP Waveguide Photon-Pair Source

Abstract: NASA awarded Small Business Innovative Research (SBIR) contracts to AdvR, Inc to develop a high generation rate source of entangled photons that could be used to explore quantum key distribution (QKD) protocols. The final product, a photon pair source using a dual-element periodically- poled potassium titanyl phosphate (KTP) waveguide, was delivered to NASA Glenn Research Center in June of 2015. This paper describes the source, its characterization, and its performance in a B92 (Bennett, 1992…

Solar Power Generation in Extreme Space Environments

Abstract: The exploration of space requires power for guidance, navigation, and control; instrumentation; thermal control; communications and data handling; and many subsystems and activities. Generating sufficient and reliable power in deep space through the use of solar arrays becomes even more challenging as solar intensity decreases and high radiation levels begin to degrade the performance of photovoltaic devices. The Extreme Environments Solar Power (EESP) project goal is to develop advanced phot…

THOMAS BUILT BUSES ( 17V317000 )

Dated: MAY 11, 2017 Daimler Trucks North America LLC (DTNA) is recalling certain 2013-2018 Thomas Built Saf-T-Liner HDX school buses. The occupant seat lap belts may have been anchored to the seat instead of the bus str…

WESTERN STAR ( 17V315000 )

Dated: MAY 11, 2017 Daimler Trucks North America LLC (DTNA) is recalling certain 2017 Freightliner Cascadia and Western Star 5700 trucks built with NFD tandem rear axles. During the hardening process, the axle assembly …

FREIGHTLINER ( 17V315000 )

Dated: MAY 11, 2017 Daimler Trucks North America LLC (DTNA) is recalling certain 2017 Freightliner Cascadia and Western Star 5700 trucks built with NFD tandem rear axles. During the hardening process, the axle assembly …