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

AbstractAs 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

Delivery of Dark Material to Vesta via Carbonaceous Chondritic Impacts

NASA's Dawn spacecraft observations of asteroid (4) Vesta reveal a surface with the highest albedo and color variation of any asteroid we have observed so far. Terrains rich in low albedo dark material (DM) have been identified using Dawn Framing Camera (FC) 0.75 {\mu}m filter images in several geologic settings: associated with impact craters (in the ejecta blanket material and/or on the crater walls and rims); as flow-like deposits or rays commonly associated with topographic highs; and as dark spots (likely secondary impacts) nearby impact craters. This DM could be a relic of ancient volcanic activity or exogenic in origin. We report that the majority of the spectra of DM are similar to carbonaceous chondrite meteorites mixed with materials indigenous to Vesta. Using high-resolution seven color images we compared DM color properties (albedo, band depth) with laboratory measurements of possible analog materials. Band depth and albedo of DM are identical to those of carbonaceous chondrite xenolith-rich howardite Mt. Pratt (PRA) 04401. Laboratory mixtures of Murchison CM2 carbonaceous chondrite and basaltic eucrite Millbillillie also show band depth and albedo affinity to DM. Modeling of carbonaceous chondrite abundance in DM (1-6 vol%) is consistent with howardite meteorites. We find no evidence for large-scale volcanism (exposed dikes/pyroclastic falls) as the source of DM. Our modeling efforts using impact crater scaling laws and numerical models of ejecta reaccretion suggest the delivery and emplacement of this DM on Vesta during the formation of the ~400 km Veneneia basin by a low-velocity (<2 km/sec) carbonaceous impactor. This discovery is important because it strengthens the long-held idea that primitive bodies are the source of carbon and probably volatiles in the early Solar System.Comment: Icarus (Accepted) Pages: 58 Figures: 15 Tables:

Evidence-based Toxicology for the 21st Century: Opportunities and Challenges

The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on “Evidence-based Toxicology for the 21st Century: Opportunities and Challenges” in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathwaybased testing methods consistent with the 2007 National Research Council report on “Toxicity Testing in the 21st Century” as well as to adopt a governance structure and work processes to move that effort forward. The workshop served to clarify evidence-based approaches and to provide food for thought on substantive and administrative activities for the EBTC. Priority activities include conducting pilot studies to demonstrate the value of evidence-based approaches to toxicology, as well as conducting educational outreach on these approaches

Evidence-based Toxicology for the 21st Century: Opportunities and Challenges

The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on “Evidence-based Toxicology for the 21st Century: Opportunities and Challenges” in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathwaybased testing methods consistent with the 2007 National Research Council report on “Toxicity Testing in the 21st Century” as well as to adopt a governance structure and work processes to move that effort forward. The workshop served to clarify evidence-based approaches and to provide food for thought on substantive and administrative activities for the EBTC. Priority activities include conducting pilot studies to demonstrate the value of evidence-based approaches to toxicology, as well as conducting educational outreach on these approaches

Mantle deformation beneath the Chicxulub impact crater

Accepted versio

Radar Observations and the Shape of Near-Earth Asteroid 2008 EV5

We observed the near-Earth asteroid 2008 EV5 with the Arecibo and Goldstone planetary radars and the Very Long Baseline Array during December 2008. EV5 rotates retrograde and its overall shape is a 400 /pm 50 m oblate spheroid. The most prominent surface feature is a ridge parallel to the asteroid's equator that is broken by a concavity 150 m in diameter. Otherwise the asteroid's surface is notably smooth on decameter scales. EV5's radar and optical albedos are consistent with either rocky or stony-iron composition. The equatorial ridge is similar to structure seen on the rubble-pile near-Earth asteroid (66391) 1999 KW4 and is consistent with YORP spin-up reconfiguring the asteroid in the past. We interpret the concavity as an impact crater. Shaking during the impact and later regolith redistribution may have erased smaller features, explaining the general lack of decameter-scale surface structure.Comment: This paper has been accepted for publication in Icarus: http://www.sciencedirect.com/science/article/B6WGF-5207B2F-4/2/d87cd2ae4da00c2b277e2dc79a532c4

Nanoindenting the Chelyabinsk meteorite to learn about impact deflection effects in asteroids

The Chelyabinsk meteorite is a highly shocked, low porosity, ordinary chondrite, probably similar to S- or Q-type asteroids. Therefore, nanoindentation experiments on this meteorite allow us to obtain key data to understand the physical properties of near-Earth asteroids (NEAs). Tests at different length scales provide information about the local mechanical properties of the minerals forming this meteorite: reduced Young's modulus, hardness, elastic recovery, and fracture toughness. Those tests are also useful to understand the potential to deflect threatening asteroids using a kinetic projectile. We found that the differences in mechanical properties between regions of the meteorite, which increase or reduce the efficiency of impacts, are not a result of compositional differences. A low mean particle size, attributed to repetitive shock, can increase hardness, while low porosity promotes a higher momentum multiplication. Momentum multiplication is the ratio between the change in momentum of a target due to an impact, and the momentum of the projectile, and therefore higher values imply more efficient impacts. In the Chelyabinsk meteorite the properties of the light-colored lithology materials facilitate obtaining higher momentum multiplication values, compared to the other regions described for this meteorite. Also, we found a low value of fracture toughness in the shock-melt veins of Chelyabinsk, which would promote the ejection of material after an impact and therefore increase the momentum multiplication. These results are relevant in the context of a future mission to test asteroid deflection, currently being studied by ESA and NASA: the Asteroid Impact and Deflection Assessment (AIDA) mission