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

CCD or CMOS camera noise characterisation

To achieve optimum imaging performance, any camera system has to be thoroughly checked before being used, particular care being given in evaluating the different contributions due to noise. Our work presents a method for characterising the different sources of noise affecting CCD or CMOS cameras, emphasising the too often overlooked pattern noise. This method is an extended and theoretical approach of the well-known photon transfer technique [1]. Experimentation on our high speed CCD imager illustrates this approach

Nitrogen solubility in molten metal and silicate at high pressure and temperature

International audienceNitrogen is the dominant gas in Earth atmosphere, but its behavior during the Earth' differentiation is poorly known. To aid in identifying the main reservoirs of nitrogen in the Earth, nitrogen solubility was determined experimentally in a mixture of molten CI-chondrite model composition and (Fe, Ni) metal alloy liquid. Experiments were performed in a laser-heated diamond-anvil cell at pressures to 18 GPa and temperatures to 2850 ± 200 K. Multi-anvil experiments were also performed at 5 and 10 GPa and 2390 ± 50 K. The nitrogen content increases with pressure in both metal and silicate reservoirs. It also increases with the iron content of the (Fe, Ni) alloy. Sieverts' formalism successfully describes the nitrogen solubility in metals up to 18 GPa. Henry's law applies to nitrogen-saturated silicate melts up to 4-5 GPa. Independently of these solubility models, it is shown that the partition coefficient of nitrogen between metal and silicate melts changes from almost 104 at ambient pressure to about 10-20 for pressures higher than 1 GPa. The pressure-dependence of the nitrogen partitioning can explain the recently suggested depletion of nitrogen relative to other volatiles in the bulk silicate Earth

Metal-silicate partitioning of iodine at high pressures and temperatures: Implications for the Earth's core and 129*Xe budgets

International audienceThe partition coefficients of iodine Dmet/sil between molten metal and molten silicate were investigated using a Laser Heated Diamond Anvil Cell (LHDAC) at pressures between 2 and 20 GPa and at ~2800 K. No pressure dependence of Dmet/sil was observed within this range, but the composition of the Fe-Ni alloy liquid phase was shown to have an effect. When the metallic liquid was alloyed with S, O and Si, there was an increase in iodine solubility in the metal. Iodine exhibited mildly siderophile behaviour across all the investigated conditions, with Dmet/sil=1.25±0.65 (2 s.d.) (Fe metal system) and Dmet/sil=4.33±1.41 (2 s.d.) (Fe-alloy). In conjunction with a revised bulk silicate Earth (BSE) concentration, it is calculated that the core could be a significant reservoir for iodine, with up to 82% of the bulk Earth's iodine budget in the core, depending on the light element content of the metal phase and the process of core formation. The composition of the metal phase appears to have a greater effect on the partitioning and sequestration of iodine than the style of core segregation. As the core likely formed while 129I was still extant, the core can also be a reservoir for radiogenic 129Xe from the decay system 129I-129Xe (T1/2=15.7 Myr). Preliminary modelling indicates that the decay of 129I in the core has the potential to generate radiogenic 129Xe concentrations that are at least two orders of magnitude greater than what has been estimated for the depleted mantle. While this may have a significant impact on the isotopic signatures of the overlying mantle, it is not yet clear how flux from the core fits within the overall picture of mantle noble gas evolutio

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