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This open online textbook on Environmental Toxicology aims at covering the field in its full width, including aspects of environmental chemistry, ecotoxicology, toxicology and risk assessment. With that, it will contribute to improving the quality, continuity and transparency of the education in environmental toxicology. We also want to make sure that fundamental insights on fate and effects of chemicals gained in the past are combined with recent approaches of effect assessment and molecular analysis of mechanisms causing toxicity. The book consists of six chapters, with each chapter being divided into several sub-chapters to enable covering all aspects relevant to the topic. All chapters are designed in a modular way, which each module having clear training goals and being flagged with a number of keywords. Most modules have an average length of 1000-2000 words, a limited number of references, and 3-5 figures and/or tables. A few modules are enlighted with short clips, animations or movies to allow better illustration of the theory. The introduction chapter of the book, for instance, contains a short interview with two key experts reflecting on the development of the field over the past 30 years. The book contains tools for self-study and training, like a (limited) number of questions at the end of each module. For the future we foresee the addition of separate exercises and other tools that may help the student in understanding the theory. The open online textbook was developed by a project team consisting of environmental toxicologists and chemists from six Dutch universities, who drafted the outline of the book and identified authors for each module. Each module is authored by one or two members of the project team. When a topic required expertise not present among the project team, an external expert, often from abroad, was asked to write the module. To guarantee the quality of the book, each module was reviewed by at least one of the members of the project team and also by an international reviewer from outside the project team. The project was supervised by an advisory board, a steering committee and educational advisors. The project team served as the editorial board. The publication of this book on an open online publication platform allows free access to anyone. It is also embedded in learning management systems used in university teaching, thereby giving students easy access. The modular composition of the book will allow teachers to design their “own” book by selecting those modules relevant for the class they teach. This will support flexible use of the book. The publication as an open online book will allow for continuous updating, so it can stay on top of new developments in the field. As it stands, about 100 modules have been finalized, another 30 modules are already available in drafts and currently in the process of being reviewed, and some are still in preparation. In spite of the large number of modules, which do provide a good basis for teaching at the bachelor of science level, we realize the book is still not complete. The book needs more advanced modules that would facilitate teaching at the master of science level and higher, as well as widening the number of topics covered. We would also like to include a broader perspective on regulatory issues so the book covers different geographic regions. Therefore, we will continue working on the book, but we also welcome any suggestions for extending the book. We invite colleagues in environmental toxicology and chemistry to take the initiative to write modules on topics still missing.

Right ventricular (RV) failure is an often undertreated entity due to its multifactorial and complex pathophysiology. In contrast to the muscular high-pressure generating left ventricle, the thinwalled crescend-shaped RV optimizes venous return and enables continuous ejection of blood into a low-resistance, highly compliant pulmonary vascular system. RV dysfunction leads to impaired RV filling with increased right atrial pressures and venous congestion. Additionally, progressive RV overload will cause leftward shifting of the intraventricular septum with reduced LV filling, low cardiac output and multi organ failure. Besides treatment of major potentially reversible precipitants, supportive treatment remains the cornerstone in the management of RV failure and comprises 1. optimizing RV preload and cardiac output and 2) reducing RV afterload. This review presents a comprehensive approach of patients with RV failure in the ICU.

In environmental risk assessment, it is essential to understand the relationship between molecular structure and fate and toxicity of organic contaminants. For surfactants, physico-chemical parameters which can reflect the interactions that determine surfactant behavior are not well defined and are therefore needed for the development of robust quantitative structure-activity relationships (QSAR). For the present study, we have measured HPLC retention times of several hydrocarbon and perfluorocarbon surfactant groups on a mixed-mode weak anion-exchange (WAX) and mixed-mode hydrophilic interaction liquid chromatography (HILIC) stationary phase. The nonionic alcohol ethoxylates are well retained on the HILIC column. Retention of anionic surfactants on the HILIC column is likely influenced by the degree of hydration of the surfactants and electrostatic repulsion from silanol groups. Less hydrated anionic surfactants (perfluoroalkyl carboxylates, perfluoroalkyl sulfonates and alkyl sulfates) show minimal hydrophilic interaction while other better hydrated anionic surfactants (alkyl carboxylates and alkyl sulfonates) are well retained. The retention mechanism of surfactants on both columns seems to be related to their degree of hydration, albeit expressed in different retention behavior: generally, retention on the WAX phase increases when retention on the HILIC phase decreases, and vice versa. The retention times from both columns were used to calculate retention factors (k’) and these were subsequently used in calculating parameters that reflect the electrostatic property (kAX) and hydrophilic property (kHILIC) that determine the interaction between the hydrophilic part of the surfactant and the stationary phase. In further development of predictive models, we suggest the use of kAX for anionic surfactants and kHILIC for nonionic surfactants.

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The sorption affinity of eighty-six charged amine structures to phospholipid monolayers (log KIAM) was determined using immobilized artificial membrane high-performance liquid chromatography (IAM-HPLC). The amine compounds covered the most prevalent types of polar groups, widely ranged in structural complexity, and included forty-seven pharmaceuticals, as well as several narcotics and pesticides. Amine type specific corrective increments were used to align log KIAM data with bilayer membrane sorption coefficients (KMW(IAM)). Using predicted sorption affinities of neutral amines, we evaluated the difference (scaling factor ΔMW) with the measured log KMW(IAM) for cationic amines. The ΔMW values were highly variable, ranging from -2.37 to +2.3 log units. For each amine type, polar amines showed lower ΔMW values than hydrocarbon based amines (CxHyN(+)). COSMOmic software was used to directly calculate the partitioning coefficient of ionic structures into a phospholipid bilayer (KDMPC-W,cation), including quaternary ammonium compounds. The resulting root mean square error (RMSE) between log KDMPC-W,cation and log KMW(IAM) was 0.83 for all eighty-six polar amines, and 0.47 for sixty-eight CxHyN(+) amines. The polar amines were then split into five groups depending on polarity and structural complexity, and corrective increments for each group were defined to improve COSMOmic predictions. Excluding only the group with sixteen complex amine structures (≥4 polar groups, Mw > 400, including several macrolide antibiotics), the resulting RMSE for corrected KDMPC-W,cation values improved to 0.45 log units for the remaining set of 138 polar and CxHyN(+) amines.

Using immobilized artificial membrane high-performance liquid chromatography (IAM-HPLC) the sorption affinity of 70 charged amine structures to phospholipids was determined. The amines contained only 1 charged moiety and no other polar groups, the rest of the molecule being aliphatic and/or aromatic hydrocarbon groups. We systematically evaluated the influence of the amine type (1°, 2°, 3° amines and quaternary ammonium), alkyl chain branching, phenyl ring positioning, charge positioning (terminal vs. central in the molecule) on the phospholipid-water partitioning coefficient (KPLIPW). These experimental results were compared with quantum-chemistry based three-dimensional (3D) molecular simulations of the partitioning of charged amines, including the most likely solute conformers, using a hydrated phospholipid bilayer in the COSMOmic module of COSMOtherm software. Both IAM-HPLC retention data and the simulations suggest that the molecular orientation of charged amines at the location in the bilayer with the lowest calculated Gibbs free energy exerts a strong influence over the partitioning within the membrane. The most favourable position of charged amines coincides with the region where the phosphate anions in the phospholipid bilayer are most abundant. Hydrocarbon units oriented in this layer are located more towards the aqueous phase and contribute less to the overall membrane affinity than hydrocarbon units extending into the more hydrophobic core of the bilayer. COSMOmic simulations explain most of the trends between the structural differences observed in IAM-HPLC based KPLIPW. For this set of cationic structures, the mean absolute difference between COSMOmic simulations and IAM-HPLC data, accounting only for amine type corrective increments, is 0.31 log units.

An explicit mathematical model describing the distribution and, in some cases, also biological activity of anthropogenic chemicals capable of multiple ionization in biological systems during the elimination period has been constructed. The biological system is represented by a catenary chain of alternating aqueous phases (with proteins and other macromolecular and low-molecular-weight cell constituents) and membranes. Pseudo-equilibrium distribution of the compounds before the start of elimination is a key assumption which has led to a substantial simplification of the mathematical description. Substitution of the model parameters by their appropriate relations to physicochemical properties of the compounds (the reference partition coefficients and dissociation constants) converts the model to the quantitative structure-activity relationship. The resulting expression satisfactorily describes the published data on growth inhibitory activity of phenol derivatives, against the ciliateTetrahymena pyriformis, as a function of their hydrophobicity and acidity. The model can be used in drug design for description of the distribution of compounds in biological test systems or in environmental sciences to predict the fate of anthropogenic chemicals in ecological systems.

Linear alkylbenzene sulfonates (LAS) are anionic high production volume surfactants used in the manufacture of cleaning products. Here, we have studied the effect of the characteristics of marine and estuarine sediments on the sorption of LAS. Sorption experiments were performed with single sediment materials (pure clays and sea sand), with sediments treated to reduce their organic carbon content, and with field marine and estuarine sediments. C12-2-LAS was used as a model compound. Sorption to the clays montmorillonite and kaolinite resulted in non-linear isotherms very similar for both clays. When reducing the organic content, sorption coefficients decreased proportionally to the fraction removed in fine grain sediments but this was not the case for the sandy sediment. The correlation of the sediment characteristics with the sorption coefficients at different surfactant concentrations showed that at concentrations below 10 µg C12-2-LAS/L, the clay content correlated better with sorption, while the organic fraction became more significant at higher concentrations.

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