A Multi-Level Analysis of World Scientific Output in Pharmacology

The purpose of this chapter is to analyse international research in “pharmacology, toxicology and pharmaceutics” (hereafter pharmacology) on the basis of the scientific papers listed in the Scopus multidisciplinary database. This primary objective is reached by answering the following questions (in the section on results). What weight does the subject area “pharmacology, toxicology and pharmaceutics” carry in world-wide science? What is the percentage contribution made by the various regions of the world to the subject area “pharmacology, toxicology and pharmaceutics”? Can certain regions be identified as leaders on that basis, as in other scientific contexts? Are emerging countries present in the field? Do the most productive countries also publish the largest number of journals? What features characterise the scientific output of companies that publish pharmacological papers

Casting a wide net: use of diverse model organisms to advance toxicology

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Hahn, M. E., & Sadler, K. C. Casting a wide net: use of diverse model organisms to advance toxicology. Disease Models & Mechanisms, 13, (2020): dmm.043844, doi: 10.1242/dmm.043844.Toxicology – the study of how chemicals interact with biological systems – has clear relevance to human health and disease. Persistent exposure to natural and synthetic chemicals is an unavoidable part of living on our planet; yet, we understand very little about the effects of exposure to the vast majority of chemicals. While epidemiological studies can provide strong statistical inference linking chemical exposure to disease, research in model systems is essential to elucidate the mechanisms of action and to predict outcomes. Most research in toxicology utilizes a handful of mammalian models that represent a few distinct branches of the evolutionary tree. This narrow focus constrains the understanding of chemical-induced disease processes and systems that have evolved in response to exposures. We advocate for casting a wider net in environmental toxicology research to utilize diverse model systems, including zebrafish, and perform more mechanistic studies of cellular responses to chemical exposures to shift the perception of toxicology as an applied science to that of a basic science. This more-inclusive perspective will enrich the field and should remain central to research on chemical-induced disease.K.C.S. acknowledges support from the National Institutes of Health (NIH)(5R01AA018886). M.E.H. acknowledges support from the National Institute ofEnvironmental Health Sciences (NIEHS) through the Boston University SuperfundResearch Program (P42ES007381) and the Woods Hole Center for Oceans andHuman Health (NIEHS grant P01ES028938 and National Science Foundation grantOCE-1840381)

Committee on Fire Toxicology

The report outlines desirable characteristics for a screening test for determining the toxicity of combustion and pyrolysis products of polymeric materials

Congener-Specific Numbering Systems for the Environmentally Relevant C4 through C8 Perfluorinated Homologue Groups of Alkyl Sulfonates, Carboxylates, Telomer Alcohols and Acids, and Their Derivatives

We introduce a congener-specific numbering system for the C4 through C8 perfluorinated homologue groups of alkyl sulfonates, carboxylates, telomer alcohols and acids, and their derivatives. Increasing length of the carbon chain beyond C3 leads to a corresponding rapid increase in the number of potential isomers (C4 =4, C5 =8, C6 =17, C7 =39, and C8 =89 congeners). There is a need for clear and unambiguous chemical shorthand to ensure accuracy and consistency in the future perfluorinated alkyl substance (PFA) literature, and to correct previous misconceptions that may have restricted research efforts into developing full-congener PFA analysis. If adopted by the research community, introduction of a numbering system at this relatively early stage of investigations into the congener-specific analysis, environmental behavior, and toxicology of PFAs would not require an arduous and difficult reassignment of historical structures and naming conventions presented in the prior art. Many PFA congeners are chiral, necessitating a consideration of their enantiospecific environmental behavior and toxicology

Metabolism of Butoxyethanol in excised human skin in vitro

Glycol ethers are widely used in industrial and household applications because their chemical and physical properties make them versatile solvents, miscible with both water and organic media. Due to the ease with which the glycol ethers are absorbed through the skin and the potential for development of adverse health effects it is important to understand the extent to which local metabolism can contribute to local and systemic toxicity. Sections of previously frozen, full thickness excised human skin samples were placed on transwell supports and placed with the underside of the skin in contact with receptor fluid. The skin surface was dosed with 115.2 mg of neat butoxyethanol and the absorption and metabolism of butoxyethanol to butoxyacetic acid monitored over time. In total 64.94 ± 0.04 mg of butoxyethanol or its metabolites were removed from the surface of the skin at 24 hours, representing the equivalent of 56% of the applied dose, the equivalent of 17.5% of the applied dose was recovered from the receiver fluid, 3% from within the skin and the remaining 23.5% of the dose was lost to the atmosphere through evaporation. After 24 hours a total of 31.5 μg of butoxyacetic acid had been produced representing approximately 0.03% of the applied dose. Therefore approximately 0.16% (31.5 μg as a percentage of the total amount of butoxyethanol reaching the receiver fluid (20.17 mg) of the absorbed butoxyethanol was metabolised to butoxyacetic acid during its passage through the skin. This suggested that, although enzyme activities capable of converting butoxyethanol to butoxyacetic acid are present in skin, metabolic conversion during percutaneous absorption was small and systemic exposure to the parent compound rather than the metabolite would occur following dermal exposure to butoxyethanol. This experiment demonstrates that it is possible to maintain metabolic activity in skin samples in an in vitro set up for short, but experimentally useful, period.Peer reviewe

Diffusion through the ex vivo vitreal body - bovine, porcine, and ovine models are poor surrogates for the human vitreous

© 2018 The Authors. Published by Elsevier B.V.The human vitreous humour is a complex gel structure whose composition and physical properties can vary considerably from person to person and also change with age. To date, the viscoelastic properties of the human vitreous gel has not been thoroughly investigated and despite many years of intensive research, an ideal vitreous substitute remains a challenge. Understanding the physical structure and properties of the vitreous is of fundamental and therapeutic interest, providing a clear insight into diffusion and transport of administered ophthalmic drug molecules into the vitreous. A number of mammalian surrogates, mainly bovine, porcine and ovine vitreous humours have been greatly used in the literature as a means of studying ophthalmic drug transport and diffusion. In this study, the mechanical, physical and rheological properties of ovine, porcine, and bovine surrogates were investigated and compared to human vitreous. In addition, a bespoke Franz cell construct was used to compare the diffusion of a model drug (i.e. fluorescein) through vitreous samples. Despite the similarity in rheological properties between bovine, porcine and human vitreous samples (p > 0.05), diffusion of fluorescein through the different vitreous samples revealed great differences in values of steady-state flux and diffusion coefficient. In addition, a first-generation vitreous mimic, composed of 4.5 mg/mL hyaluronic acid with complex viscosity of 0.3 ± 0.01 Pa has been evaluated and was demonstrated to be a better mimic of the human vitreous than the mammalian samples investigated.Peer reviewe

An Undergraduate Toxicology Seminar Focusing on Ethical Reasoning and Communication Skill Development

The development of an undergraduate major in toxicology at Nazareth College provided the opportunity to develop a one-credit Principles of Toxicology Seminar designed to address ethical reasoning skills and communication (both oral and written), areas which can be challenging to address in traditional courses and which have been noted to be areas of deficiency in toxicology graduates. The seminar is a co-requisite to Principles of Toxicology, the introductory course in the major, and is built around the study of 5-7 environmental issues selected by the students. The issues are introduced through readings, documentaries, and student small group oral “environmental issue presentations.” Students then write “policy papers” through which they survey the primary literature to determine the health effects of the chemical(s) implicated in the issue and make a determination of whether they believe the data support the current exposure limits set by regulatory agencies. Student evaluations of the seminar using the IDEA metric indicate substantial progress on objectives related to critical thinking and oral and written communication skill development, among others, as well as overall very positive views on the seminar itself and the field of toxicology. Thus, this seminar may serve as a pedagogical model of a course that engages students with real-world environmental issues of interest to them, while facilitating the development of the ethical reasoning and communication skills that can be challenging to address in the traditional curriculum