Construction of an In Silico Structural Profiling Tool Facilitating Mechanistically Grounded Classification of Aquatic Toxicants.

The performance of chemical safety assessment within the domain of environmental toxicology is often impeded by a shortfall of appropriate experimental data describing potential hazards across the many compounds in regular industrial use. In silico schemes for assigning aquatic-relevant modes or mechanisms of toxic action to substances, based solely on consideration of chemical structure, have seen widespread employment─including those of Verhaar, Russom, and later Bauer (MechoA). Recently, development of a further system was reported by Sapounidou, which, in common with MechoA, seeks to ground its classifications in understanding and appreciation of molecular initiating events. Until now, this Sapounidou scheme has not seen implementation as a tool for practical screening use. Accordingly, the primary purpose of this study was to create such a resource─in the form of a computational workflow. This exercise was facilitated through the formulation of 183 structural alerts/rules describing molecular features associated with narcosis, chemical reactivity, and specific mechanisms of action. Output was subsequently compared relative to that of the three aforementioned alternative systems to identify strengths and shortcomings as regards coverage of chemical space

A scheme to evaluate structural alerts to predict toxicity – Assessing confidence by characterising uncertainties

Structure-activity relationships (SARs) in toxicology have enabled the formation of structural rules which, when coded as structural alerts, are an essential tool in in silico toxicology. Whilst other in silico methods have approaches for their evaluation, there is no formal process to assess the confidence that may be associated with a structural alert. This investigation proposes twelve criteria to assess the uncertainty associated with structural alerts, allowing for an assessment of confidence. The criteria are based around the stated purpose, description of the chemistry, toxicology and mechanism, performance and coverage, as well as corroborating and supporting evidence of the alert. Alerts can be given a confidence assessment and score, enabling the identification of areas where more information may be beneficial. The scheme to evaluate structural alerts was placed in the context of various use cases for industrial and regulatory applications. The analysis of alerts, and consideration of the evaluation scheme, identifies the different characteristics an alert may have, such as being highly specific or generic. These characteristics may determine when an alert can be used for specific uses such as identification of analogues for read-across or hazard identification

Development of an Enhanced Mechanistically-Driven Mode of Action Classification Scheme for Adverse Effects in Environmental Species

This study developed a novel classification scheme to assign chemicals to a verifiable mechanism of (eco)toxicological action to allow for grouping, read-across and in silico model generation. The new classification scheme unifies and extends existing schemes and has at its heart, direct reference to molecular initiating events (MIEs) promoting adverse outcomes. The scheme is based on three broad domains of toxic action representing non-specific toxicity (e.g. narcosis), reactive mechanisms (e.g. electrophilicity and free radical action) and specific mechanisms (e.g. associated with enzyme inhibition). The scheme is organised at three further levels of detail beyond broad domains to separate out mechanistic group, specific mechanism and the MIEs responsible. Novelty in this approach comes from the reference to taxonomic diversity within the classification, transparency, quality of supporting evidence relating to MIEs and that it can be updated readily

Retificação cilíndrica do aço VP50 utilizando o rebolo de carbeto de silício verde com a técnica de MQL

RESUMO A retificação é um processo de alta geração de calor, portanto, com seu uso em larga escala, a pesquisa e desenvolvimento de novas técnicas de lubri-refrigeração se fazem necessários, visando respeitar as leis ambientais, preservar a saúde do operador e reduzir custos de produção. Deve-se, então, buscar soluções que mantenham os mesmos parâmetros de qualidade, acabamento e os mesmos efeitos tecnológicos. Um dos métodos propostos para este fim é o MQL (mínima quantidade de lubrificação), que utiliza uma mistura de ar com baixo fluxo de óleo a elevada pressão. O aço a ser utilizado como corpo de prova foi VP 50, muito usado na indústria em moldes para injeção de termoplásticos. O rebolo utilizado foi o de carbeto de silício verde, com ligante vitrificado. Apresentam boas características térmicas, estabilidade química elevada na retificação ferros fundidos, materiais não ferrosos e não metálicos. A análise dos resultados foi feita através avaliação das variáveis de saída do processo, tais como rugosidade, emissão acústica, circularidade, microscopia óptica (para verificação de dano térmico) e microdureza. Dentre os resultados evidenciados, a técnica MQL demonstrou ser superior ao método convencional apenas nos parâmetros de circularidade e desgaste diametral do rebolo, sendo que não houve alteração microestrutural em ambos os métodos de lubrificação