| 1. |
- Leist, Marcel, et al.
(författare)
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Adverse outcome pathways : opportunities, limitations and open questions
- 2017
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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 91:11, s. 3477-3505
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Tidskriftsartikel (refereegranskat)abstract
- Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event erelationships (KER). Although this approach to formalize mechanistic toxicological information only started in 2010, over 200 AOPs have already been established. At this stage, new requirements arise, such as the need for harmonization and re-assessment, for continuous updating, as well as for alerting about pitfalls, misuses and limits of applicability. In this review, the history of the AOP concept and its most prominent strengths are discussed, including the advantages of a formalized approach, the systematic collection of weight of evidence, the linkage of mechanisms to apical end points, the examination of the plausibility of epidemiological data, the identification of critical knowledge gaps and the design of mechanistic test methods. To prepare the ground for a broadened and appropriate use of AOPs, some widespread misconceptions are explained. Moreover, potential weaknesses and shortcomings of the current AOP rule set are addressed (1) to facilitate the discussion on its further evolution and (2) to better define appropriate vs. less suitable application areas. Exemplary toxicological studies are presented to discuss the linearity assumptions of AOP, the management of event modifiers and compensatory mechanisms, and whether a separation of toxicodynamics from toxicokinetics including metabolism is possible in the framework of pathway plasticity. Suggestions on how to compromise between different needs of AOP stakeholders have been added. A clear definition of open questions and limitations is provided to encourage further progress in the field.
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| 2. |
- Haanes, Jan Vilis, et al.
(författare)
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"Symptoms associated with environmental factors" (SAEF) - Towards a paradigm shift regarding "idiopathic environmental intolerance" and related phenomena
- 2020
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Ingår i: Journal of Psychosomatic Research. - : Elsevier. - 0022-3999 .- 1879-1360. ; 131
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Tidskriftsartikel (refereegranskat)abstract
- Health conditions characterized by symptoms associated with chemical, physical and biological environmental factors unrelated to objectifiable pathophysiological mechanisms are often labelled by the general term "idiopathic environmental intolerances". More specific, exposure-related terms are also used, e.g. "multiple chemical sensitivities", "electromagnetic hypersensitivity" and "candidiasis hypersensitivity". The prevalence of the conditions varies from a few up to more than 50%, depending on definitions and populations. Based on evolving knowledge within this field, we provide arguments for a paradigm shift from terms focusing on exposure and intolerance/(hyper-)sensitivity towards a term more in line with the perceptual elements that seem to underlie these phenomena. Symptoms caused by established pathophysiologic mechanisms should not be included, e.g. allergic or toxicological conditions, lactose intolerance or infections. We discuss different alternatives for a new term/concept and end up proposing an open and descriptive term, "symptoms associated with environmental factors" (SAEF), including a definition. "Symptoms associated with environmental factors" both is in line with the current knowledge and acknowledge the experiences of the afflicted persons. Thus, the proposed concept is likely to facilitate therapy and communication between health professionals and afflicted persons, and to provide a base for better understanding of such phenomena in healthcare, society and science.
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| 3. |
- Pitron, Victor, et al.
(författare)
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Electrohypersensitivity is always real
- 2023
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 218
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Tidskriftsartikel (refereegranskat)abstract
- Highlights:Electrohypersensitivty (EHS) represents a severely disabling condition.Symptom reports in EHS are unrelated to actual electromagnetic field exposure.A reductionist bio-electromagnetic approach fails to explain EHS.Empirical evidence suggests that nocebo effects strongly contribute to EHS.Spreading the myth about a (non-existing) EHS epidemic causes harm.
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| 4. |
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| 5. |
- Bal-Price, Anna, et al.
(författare)
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Putative adverse outcome pathways relevant to neurotoxicity
- 2015
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Ingår i: Critical reviews in toxicology. - : Informa UK Limited. - 1040-8444 .- 1547-6898. ; 45:1, s. 83-91
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Forskningsöversikt (refereegranskat)abstract
- The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.
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