Toxicity testing in the 21st century: progress in the past decade and future perspectives.

Advances in the biological sciences have led to an ongoing paradigm shift in toxicity testing based on expanded application of high-throughput in vitro screening and in silico methods to assess potential health risks of environmental agents. This review examines progress on the vision for toxicity testing elaborated by the US National Research Council (NRC) during the decade that has passed since the 2007 NRC report on Toxicity Testing in the 21st Century (TT21C). Concomitant advances in exposure assessment, including computational approaches and high-throughput exposomics, are also documented. A vision for the next generation of risk science, incorporating risk assessment methodologies suitable for the analysis of new toxicological and exposure data, resulting in human exposure guidelines is described. Case study prototypes indicating how these new approaches to toxicity testing, exposure measurement, and risk assessment are beginning to be applied in practice are presented. Overall, progress on the 20-year transition plan laid out by the US NRC in 2007 has been substantial. Importantly, government agencies within the United States and internationally are beginning to incorporate the new approach methodologies envisaged in the original TT21C vision into regulatory practice. Future perspectives on the continued evolution of toxicity testing to strengthen regulatory risk assessment are provided.

Development of a consumer product ingredient database for chemical exposure screening and prioritization.

Consumer products are a primary source of chemical exposures, yet little structured information is available on the chemical ingredients of these products and the concentrations at which ingredients are present. To address this data gap, we created a database of chemicals in consumer products using product Material Safety Data Sheets (MSDSs) publicly provided by a large retailer. The resulting database represents 1797 unique chemicals mapped to 8921 consumer products and a hierarchy of 353 consumer product "use categories" within a total of 15 top-level categories. We examine the utility of this database and discuss ways in which it will support (i) exposure screening and prioritization, (ii) generic or framework formulations for several indoor/consumer product exposure modeling initiatives, (iii) candidate chemical selection for monitoring near field exposure from proximal sources, and (iv) as activity tracers or ubiquitous exposure sources using "chemical space" map analyses. Chemicals present at high concentrations and across multiple consumer products and use categories that hold high exposure potential are identified. Our database is publicly available to serve regulators, retailers, manufacturers, and the public for predictive screening of chemicals in new and existing consumer products on the basis of exposure and risk.

Force networks and elasticity in granular silos.

We have made experimental observations of the force networks within a two-dimensional granular silo similar to the classical system of Janssen. Models like that of Janssen predict that pressure within a silo saturates with depth as the result of vertical forces being redirected to the walls of the silo where they can then be carried by friction. We use photoelastic particles to obtain information not available in previous silo experiments --the internal force structure. We directly compare various predictions with the results obtained by averaging ensembles of experimentally obtained force networks. We identify several differences between the mean behavior in our system and that predicted by Janssen-like models: We find that the redirection parameter describing how the force network transfers vertical forces to the walls varies with depth. We find that changes in the preparation of the material can cause the pressure within the silo to either saturate or to continue building with depth. Most strikingly, we observe a nonlinear response to overloads applied to the top of the material in the silo. For larger overloads we observe the previously reported "giant overshoot" effect where overload pressure decays only after an initial increase (G. Ovarlez et al., Phys. Rev. E 67, 060302(R) (2003)). For smaller overloads we find that additional pressure propagates to great depth. Analysis of the differences between the inter-grain contact and force networks suggests that, for our system, when the load and the particle weight are comparable, particle elasticity acts to stabilize the force network, allowing deep propagation. For larger loads, the force network rearranges, resulting in the expected, Janssen-like behavior. Thus, a meso-scale network phenomenon results in an observable nonlinearity in the mean pressure profile.

Ratchet-induced segregation and transport of nonspherical grains.

We consider through simulations the behavior of elongated grains on a vibrating ratchet-shaped base. We observe differences in layer velocity profile and in net grain velocity for grains that are composed of one, two, or three collinear spheres. In the case of mixtures of different species of grains, we demonstrate layer-by-layer variation in the average velocity as well as layer segregation of species, and show that horizontal separation of the species can be achieved using this geometry. We also find that the addition of a small number of shorter grains to a sample of long grains provides a lubrication effect that increases the velocity of the long grains.