The potential use of kraft lignins as natural ingredients for cosmetics: Evaluating their photoprotective activity and skin irritation potential.

The cosmetics market has recently undergone changes as consumers increasingly seek sustainable products. In this context, agro-derived lignins have the potential for cosmetics applications. Thus, this study investigated the photoprotective activity and skin irritation potential (OECD TG 439 with SkinVitro-RHE, an in-house reconstructed human epidermis (RHE) model) of a kraft lignin (LE) and two LE-derived lignins modified by enzymatic reactions to achieve higher molecular weight (Mw) (R1: intermediate Mw and E60: highest Mw). Results showed that LE and R1 lignins present adequate photoprotective activity with averages Sun Protection Factor (SPF) of 33.8 ± 0.02 and 22.7 ± 0.04, respectively. The E60 also present adequate SPF (22.4 ± 0.2); however, due to its poor solubility, this lignin has potential application as a physical filter. In terms of safety, these lignins did not cause skin irritation or cellular and structural damage to the epidermis. Additionally, using an analysis based on the autofluorescence feature of lignin, no sign of the tested lignins was found in exposed RHE models, indicating that these three lignins did not penetrate the skin. Altogether, the results indicate a promising application of kraft lignins for sunscreen products regarding safer alternatives and product sustainability. Also, the SkinVitro-RHE showed to be a good model for evaluating the skin irritation potential of substances, including natural cosmetic ingredients.

A Robust, Mechanistically Based In Silico Structural Profiler for Hepatic Cholestasis.

Owing to the primary role which it holds within metabolism of xenobiotics, the liver stands at heightened risk of exposure to, and injury from, potentially hazardous substances. A principal manifestation of liver dysfunction is cholestasis-the impairment of physiological bile circulation from its point of origin within the organ to the site of action in the small intestine. The capacity for early identification of compounds liable to exert cholestatic effects is of particular utility within the field of pharmaceutical development, where contribution toward candidate attrition is great. Shortcomings associated with the present in vitro methodologies forecasting cholestasis render their predictivity questionable, permitting scope for the adoption of computational toxicology techniques. As such, the intention of this study has been to construct an in silico profiler, founded upon clinical data, highlighting structural motifs most reliably associated with the end point. Drawing upon a list of >1500 small molecular drugs, compiled and annotated by Kotsampasakou, E. and Ecker, G. F. (J. Chem. Inf. Model. 2017, 57, 608-615), we have formulated a series of 15 structural alerts. These describe fragments intrinsic within distinct pharmaceutical classes including psychoactive tricyclics, ß-lactam antimicrobials, and estrogenic/androgenic steroids. Description of the coverage and selectivity of each are provided, alongside consideration of the underlying reactive mechanisms and relevant structure-activity concerns. Provision of mechanistic anchoring ensures that potential exists for framing within the adverse outcome pathway paradigm-the chemistry conveyed through the alert, in particular enabling rationalization at the level of the molecular initiating event.

Incorporating lines of evidence from New Approach Methodologies (NAMs) to reduce uncertainties in a category based read-across: A case study for repeated dose toxicity.

A group of triazole compounds was selected to investigate the confidence that may be associated with read-across of a complex data gap: repeated dose toxicity. The read-across was evaluated using Assessment Elements (AEs) from the European Chemicals Agency's (ECHA's) Read-Across Assessment Framework (RAAF), alongside appraisal of associated uncertainties. Following an initial read-across based on chemical structure and properties, uncertainties were reduced by the integration of data streams such as those from New Approach Methodologies (NAM) and other existing data. In addition, addressing the findings of the ECHA RAAF framework, complemented with specific questions concerning uncertainties, increased the confidence that can be placed in read-across. Although a data rich group of compounds with a strong mechanistic basis was analysed, it was clearly demonstrated that NAM data available from publicly available resources could be applied to support read-across. It is acknowledged that most read-across studies will not be so data rich or mechanistically robust, therefore some targeted experimentation may be required to fill the data gaps. In this sense, NAMs should constitute new experimental tests performed with the specific goal of reducing the uncertainties and demonstrating the read-across hypothesis.

Microscopia ótica de alta resoluçäo: adaptaçäo do método e sua aplicaçäo ao estudo da leptospirose experimental em cobaias / High resolution light microscopy: adaptation of the method and its use in the study of experimental leptospirosis in guinea pigs

As lesöes morfológicas em parênquina e vasos de fígado e rim foram estudadas em um lote de cobaias infectadas experimentalmente com Leptospira interrogans sorogrupos icterohaemorrhagiae, em comparaçäo com um grupo de cobaias normais näo infectadas. O material foi analisado a microscopia óptica convencional (MOC), através da inclusäo em parafina, e a de alta resoluçäo (MOAR), esta com cortes de um micrômetro de espessura e até-96 mm2 de superfície, em tecido incluido em glicol-metacrilato. A utilizaçäo pela primeira vez da microscopia óptica de alta resoluçäo para o estudo da leptospirose revelou novos aspectos da doença, na medida em que permitiu análise de detalhes celulares e visäo de conjunto do quadro histológico na mesma amostra. Assim foi possível constatar se tanto alteraçöes da coesäo intercelular como especializaçöes de membranas, incluindo borda em escova, e vesículas de pinocitose, além da distribuiçäo intracelular de organelas saculares, provavelmente mitocondrias. A introduçäo desta metodologia de baixo custo e fácil execuçäo poderátrazer contribuiçöes úteis a histotecnologia com objetivos diagnósticos e em pesquisa.