Toward Good Read-Across Practice (GRAP) guidance.

Grouping of substances and utilizing read-across of data within those groups represents an important data gap filling technique for chemical safety assessments. Categories/analogue groups are typically developed based on structural similarity and, increasingly often, also on mechanistic (biological) similarity. While read-across can play a key role in complying with legislations such as the European REACH regulation, the lack of consensus regarding the extent and type of evidence necessary to support it often hampers its successful application and acceptance by regulatory authorities. Despite a potentially broad user community, expertise is still concentrated across a handful of organizations and individuals. In order to facilitate the effective use of read-across, this document aims to summarize the state-of-the-art, summarizes insights learned from reviewing ECHA published decisions as far as the relative successes/pitfalls surrounding read-across under REACH and compile the relevant activities and guidance documents. Special emphasis is given to the available existing tools and approaches, an analysis of ECHA's published final decisions associated with all levels of compliance checks and testing proposals, the consideration and expression of uncertainty, the use of biological support data and the impact of the ECHA Read-Across Assessment Framework (RAAF) published in 2015

Demonstrating the reliability of in vivo metabolomics based chemical grouping:towards best practice

While grouping/read-across is widely used to fill data gaps, chemical registration dossiers are often rejected due to weak category justifications based on structural similarity only. Metabolomics provides a route to robust chemical categories via evidence of shared molecular effects across source and target substances. To gain international acceptance, this approach must demonstrate high reliability, and best-practice guidance is required. The MetAbolomics ring Trial for CHemical groupING (MATCHING), comprising six industrial, government and academic ring-trial partners, evaluated inter-laboratory reproducibility and worked towards best-practice. An independent team selected eight substances (WY-14643, 4-chloro-3-nitroaniline, 17α-methyl-testosterone, trenbolone, aniline, dichlorprop-p, 2-chloroaniline, fenofibrate); ring-trial partners were blinded to their identities and modes-of-action. Plasma samples were derived from 28-day rat tests (two doses per substance), aliquoted, and distributed to partners. Each partner applied their preferred liquid chromatography–mass spectrometry (LC–MS) metabolomics workflows to acquire, process, quality assess, statistically analyze and report their grouping results to the European Chemicals Agency, to ensure the blinding conditions of the ring trial. Five of six partners, whose metabolomics datasets passed quality control, correctly identified the grouping of eight test substances into three categories, for both male and female rats. Strikingly, this was achieved even though a range of metabolomics approaches were used. Through assessing intrastudy quality-control samples, the sixth partner observed high technical variation and was unable to group the substances. By comparing workflows, we conclude that some heterogeneity in metabolomics methods is not detrimental to consistent grouping, and that assessing data quality prior to grouping is essential. We recommend development of international guidance for quality-control acceptance criteria. This study demonstrates the reliability of metabolomics for chemical grouping and works towards best-practice

A cross-sectional transmission electron microscopy study of iron recovered from a laser-heated diamond anvil cell

This paper discusses the use of a focused ion beam for the preparation of cross-sectional transmission electron microscopy specimens from small samples, typically 150 micron in diameter, that have been recovered from a laser-heated diamond anvil cell. We present preliminary observations of iron melted with helium as the pressure-transmitting medium to pressures near 4 GPa. The project is designed to investigate entrapment mechanisms of the inert gases in metals and silicates at high pressure and temperatures

Argon solubility drop in silicate melts at high pressures: a review of recent experiments

Controversy surrounding Ar solubility in silicate melts at high pressure (HP) has led us to perform a suite of Ar solubility experiments on silicate melts with a variety of compositions up to ~ 25 GPa. These results of these experiments strongly constrain the structure of the melts at HP, and confirm the features first observed in olivine composition melts, resolving the controversy over the solubility of Ar in silicate melts at the upper mantle conditions. The Ar solubility experiments show that argon contents in aluminosilicate melts reach a maximum that persists to pressures as high as 17 GPa well above that observed for Al-free melts. A subsequent drop in argon solubility correlates well with the expected void loss in the melt structure predicted by molecular dynamics simulations [Nevins, D. and Spera, F.J. (1998). Molecular dynamics simulations of molten CaAl2Si2O8: dependence of structure and properties on pressure, Am. Mineral. 83: 1220–1230]. This discontinuous drop for argon solubility at high pressure should be a universal behaviour of silicate melts, and our experiments show that the onset of pressure for reduced argon solubility has a positive correlation with the Al/(Al + Si) ratio of the melts. Thus the experimental data for Ar solubility are entirely consistent with known natural samples from upper mantle conditions

Comment on: Melting behavior of SiO<SUB>2</SUB> up to 120 GPa (Andrault et al. 2020)

International audienceThe additional work we have done using our new laser heating in the diamond anvil cell system since the publication of Andrault et al. (Phys Chem Mineral 47(2), 2020) leads us to the conclusion that there was a systematic bias in the determination of temperature. First, the temperature of the W-lamp used for the calibration of the optical system was overestimated by ~ 22 K at 2273 K. Then, we made the assumption that hot SiO2 was a grey-body (constant emissivity ε(λ)), while the available measurements suggest instead that ε(λ) of SiO2 is similar to that of tungsten. Applying these two corrections lowers the SiO2 melting temperatures significantly. In LMV, we performed a new experimental determination of the SiO2 melting temperature, at 5000 (200) K and ~ 70 (4) GPa, which is well compatible with the amplitude of the correction proposed. The reevaluation of the melting temperature profile does not affect largely the interpretations or the main conclusions presented in Andrault et al. (Phys Chem Mineral 47(2), 2020). Within the stability field of stishovite, the melting curve still presents a relatively sharp change of slope at P-T recalculated as ~ 40 GPa and ~ 4800 K. It is related to a change of the melt structure. At higher pressures, the melting curve is almost flat up to the subsolidus transition from stishovite to the CaCl2-form around 85 GPa, where the slope of the melting curve increases again up to ~ 120 GPa. We present corrected figures and tables of the original publication

Martensitic fcc-hcp transformation pathway in solid krypton and xenon and its effect on their equations of state

International audienceThe martensitic transformation is a fundamental physical phenomenon at the origin of important industrial applications. However, the underlying microscopic mechanism, which is of critical importance to explain the outstanding mechanical properties of martensitic materials, is still not fully understood. This is because for most martensitic materials the transformation is a fast process that makes in situ studies extremely challenging. Noble solids krypton and xenon undergo a progressive pressure-induced face-centered cubic (fcc) to hexagonal close-packed (hcp) martensitic transition with a very wide coexistence domain. Here, we took advantage of this unique feature to study the detailed transformation progress at the atomic level by employing in situ x-ray diffraction and absorption spectroscopy. We evidenced a four-stage pathway and suggest that the lattice mismatch between the fcc and hcp forms plays a key role in the generation of strain. We also determined precisely the effect of the transformation on the compression behavior of these materials

Replication Data for: The Diverse Planetary Ingassing/Outgassing Paths Produced over Billions of Years of Magmatic Activity

The C-H-O-N-S elements that constitute the outgassed atmosphere and exosphere have likely been delivered by chondritic materials to the Earth during planetary accretion and subsequently processed over billions of years of planetary differentiation. Although these elements are generally considered to be volatile, a large part of the accreted C-H-O-N-S on Earth must have been sequestered in the core and mantle, with the remaining part concentrated at the Earth’s surface (exosphere: atmosphere+ocean+crust). The likely reason for this is that, depending on the prevailing pressure (P), temperature (T) and oxidation state (oxygen fugacity, fO2) in the planet’s interior, the C-H-O-N-S elements can behave as siderophile, lithophile, refractory, magmatophile, or atmophile. It is not clear if these elements might be sequestered in the interiors of planets elsewhere, since the governing parameters of P-T-fO2 during the diverse magmatic processes controlling magmatic differentiation vary greatly over time and from planet to planet. The magma ocean outgassed the first atmosphere, which was probably also the largest in terms of mass, but its nature and composition remain poorly known. Meanwhile, a significant, but unknown, part of the accreted C-H-O-N-S elements was sequestered in the core. These will probably never be liberated into the atmosphere. A secondary atmosphere was then fuelled by volcanism, driven by mantle convection and most likely enhanced by plate tectonics. The Earth still has active volcanism, and the volume and volatile contents of its magma are closely linked to geodynamics. Earth’s volcanoes have long emitted relatively oxidized gases, in contrast to Mars and Mercury. Mantle oxidation state seems to increase with planetary size, although the role of plate tectonics in changing the Earth’s mantle oxidation state remains poorly understood. Water contents of magma from elsewhere in the solar system are not so different from those produced by the Earth’s depleted mantle. Other elements (e.g. N, S, C) are unevenly distributed. A great diversity of speciation and quantity of magmatic gas emitted is found in planetary systems, with the key inputs being: 1 – degassing of the magma ocean, 2 – mantle oxidation state (and its evolution), and 3 – plate tectonics (vs. other styles of mantle convection). Many other parameters can affect these three inputs, of which planetary size is probably one of the most important

182W evidence for core-mantle interaction in the source of mantle plumes

International audienceTungsten isotopes are the ideal tracers of core-mantle chemical interaction. Given that W is moderately siderophile, it preferentially partitioned into the Earth’s core during its segregation, leaving the mantle depleted in this element. In contrast, Hf is lithophile, and its short-lived radioactive isotope 182Hf decayed entirely to 182W in the mantle after metal-silicate segregation. Therefore, the 182W isotopic composition of the Earth’s mantle and its core are expected to differ by about 200 ppm. Here, we report new high precision W isotope data for mantle-derived rock samples from the Paleoarchean Pilbara Craton, and the Réunion Island and the Kerguelen Archipelago hotspots. Together with other available data, they reveal a temporal shift in the 182W isotopic composition of the mantle that is best explained by core-mantle chemical interaction. Core-mantle exchange might be facilitated by diffusive isotope exchange at the core-mantle boundary, or the exsolution of W-rich, Si-Mg-Fe oxides from the core into the mantle. Tung-sten-182 isotope compositions of mantle-derived magmas are similar from 4.3 to 2.7 Ga and decrease afterwards. This change could be related to the onset of the crystallisation of the inner core or to the initiation of post-Archean deep slab subduction that more efficiently mixed the mantle