alternative approach for potency assessment in vitro methods

Over the last decade, incredible progress has been made in the development of non-animal tests to assess contact hypersensitivity. Four methods have been successfully validated and Organisation for Economic Co-operation and Development (OECD) guidelines are available or soon will be. Currently validated methods are useful for hazard identification, classification and labeling. However, to achieve a complete replacement of animals in skin sensitization assessment, dose-response information and evaluation of relative skin sensitizing potency to support effective risk assessment are necessary. In this context, potency is based on the concentration of chemicals needed to induce a positive response. This will require a better understanding of the mechanisms determining potency, including pathway analysis and marker signature identification (selection of an appropriate immune-mediated response to serve as the basis), together with quantitative and qualitative correlations between marker signatures and potency of chemicals in relation with T cell responses. This review aims to discuss the state-of-the-art in the field of in vitro assessment of the no induction sensitization level of contact sensitizers

NEIU Magazine- Summer 2003

https://neiudc.neiu.edu/neiumag/1007/thumbnail.jp

An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility of In Vitro and In Silico Methods in a Regulatory Context

Sensitization of the respiratory tract is an important occupational health challenge, and understanding the mechanistic basis of this effect is necessary to support the development of toxicological tools to detect chemicals that may cause it. Here we use the adverse outcome pathway (AOP) framework to organize information that may better inform our understanding of sensitization of the respiratory tract, building on a previously published skin sensitization AOP, relying on literature evidence linked to low-molecular-weight organic chemicals and excluding other known respiratory sensitizers acting via different molecular initiating events. The established key events (KEs) are as follows: (1) covalent binding of chemicals to proteins, (2) activation of cellular danger signals (inflammatory cytokines and chemokines and cytoprotective gene pathways), (3) dendritic cell activation and migration, (4) activation, proliferation, and polarization of T cells, and (5) sensitization of the respiratory tract. These events mirror the skin sensitization AOP but with specific differences. For example, there is some evidence that respiratory sensitizers bind preferentially to lysine moieties, whereas skin sensitizers bind to both cysteine and lysine. Furthermore, exposure to respiratory sensitizers seems to result in cell behavior for KEs 2 and 3, as well as the effector T cell response, in general skewing toward cytokine secretions predominantly associated with T helper 2 (Th2) response. Knowledge gaps include the lack of understanding of which KE(s) drive the Th2 polarization. The construction of this AOP may provide insight into predictive tests that would in combination support the discrimination of respiratory-sensitizing from non- and skin-sensitizing chemicals, a clear regulatory need

Allergic sensitization: screening methods

Experimental in silico, in vitro, and rodent models for screening and predicting protein sensitizing potential are discussed, including whether there is evidence of new sensitizations and allergies since the introduction of genetically modified crops in 1996, the importance of linear versus conformational epitopes, and protein families that become allergens. Some common challenges for predicting protein sensitization are addressed: (a) exposure routes; (b) frequency and dose of exposure; (c) dose-response relationships; (d) role of digestion, food processing, and the food matrix; (e) role of infection; (f) role of the gut microbiota; (g) influence of the structure and physicochemical properties of the protein; and (h) the genetic background and physiology of consumers. The consensus view is that sensitization screening models are not yet validated to definitively predict the de novo sensitizing potential of a novel protein. However, they would be extremely useful in the discovery and research phases of understanding the mechanisms of food allergy development, and may prove fruitful to provide information regarding potential allergenicity risk assessment of future products on a case by case basis. These data and findings were presented at a 2012 international symposium in Prague organized by the Protein Allergenicity Technical Committee of the International Life Sciences Institute’s Health and Environmental Sciences Institute

Developing a framework for assessing respiratory sensitization: A workshop report

Respiratory tract sensitization can have significant acute and chronic health implications. While induction of respiratory sensitization is widely recognized for some chemicals, validated standard methods or frameworks for identifying and characterizing the hazard are not available. A workshop on assessment of respiratory sensitization was held to discuss the current state of science for identification and characterization of respiratory sensitizer hazard, identify information facilitating development of validated standard methods and frameworks, and consider the regulatory and practical risk management needs. Participants agreed on a predominant Th2 immunological mechanism and several steps in respiratory sensitization. Some overlapping cellular events in respiratory and skin sensitization are well understood, but full mechanism(s) remain unavailable. Progress on non-animal approaches to skin sensitization testing, ranging from in vitro systems, –omics, in silico profiling, and structural profiling were acknowledged. Addressing both induction and elicitation phases remains challenging. Participants identified lack of a unifying dose metric as increasing the difficulty of interpreting dosimetry across exposures. A number of research needs were identified, including an agreed list of respiratory sensitizers and other asthmagens, distinguishing between adverse effects from immune-mediated versus non immunological mechanisms. A number of themes emerged from the discussion regarding future testing strategies, particularly the need for a tiered framework respiratory sensitizer assessment. These workshop present a basis for moving towards a weight-of-evidence assessment

Análisis de la educación ambiental y la educación para el desarrollo sostenible en la enseñanza de la ingeniería

Tesis por compendio de publicaciones[ES] Los modelos de educación en temas ambientales predominantes en el mundo son la educación ambiental (EA) y la educación para el desarrollo sostenible (EDS). La EA se distingue especialmente por el interés en la protección y conservación de los recursos naturales. Este rasgo ha hecho que sea un buen pendón para los discursos políticos y demagógicos, especialmente en lugares como Latinoamérica. Por su parte, la EDS es más reciente, su fuerza como modelo de educación comenzó en la primera década del siglo XX, una de sus características es que es un modelo antropocéntrico e impulsador del desarrollo económico como principio para lograr el desarrollo social y el equilibro ambiental. La educación superior, y en especial las ingenierías, no son ajenas a la disputa por la selección del modelo que debe ser incluido dentro de sus enseñanzas. Con esta tesis doctoral se buscó establecer el grado de conocimiento y aplicabilidad de la EA y la EDS en Latinoamérica y con un especial énfasis en Colombia. Se logró encontrar que, a nivel global, Latinoamérica es una de las regiones con menos conocimiento de la EDS y con un fuerte arraigo de la EA, en comparación con otras regiones como Europa, donde predomina la EDS. Así mismo, se identificaron los rasgos que caracterizan la EA en Latinoamérica, en la enseñanza de las ingenierías, así como la falta de conocimiento de la EDS por parte de los profesores y estudiantes de dichas titulaciones. Finalmente, se propuso una estrategia mediadora entre la EA y la EDS con la finalidad de incluirlas dentro de los planes de estudio de las ingenierías, mediante la propuesta de una nueva asignatura. En este sentido, se evidenciaron las ventajas y desventajas de esta metodología a partir de su implementación en el programa de ingeniería ambiental de la Universidad Santo Tomás en Colombia