{"id":822,"date":"2026-01-29T22:31:08","date_gmt":"2026-01-29T22:31:08","guid":{"rendered":"https:\/\/science.peta.org\/toxicity-assessment\/"},"modified":"2026-07-02T14:45:36","modified_gmt":"2026-07-02T14:45:36","slug":"evaluacion-de-la-toxicidad","status":"publish","type":"page","link":"https:\/\/science.peta.org\/es\/evaluacion-de-la-toxicidad\/","title":{"rendered":"Evaluaci\u00f3n de la toxicidad"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">A continuaci\u00f3n, se detallan las oportunidades para eliminar o reducir significativamente el uso de animales en la evaluaci\u00f3n de la toxicidad de sustancias en el contexto de los requisitos regulatorios en esta materia. Tambi\u00e9n se describen las \u00e1reas en las que se requiere un mayor apoyo para desarrollar m\u00e9todos innovadores que sean relevantes para la evaluaci\u00f3n de la salud humana y los par\u00e1metros ambientales.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">En caso de que las pruebas sean requeridas con fines regulatorios, deben consultarse fuentes directas, como los sitios web de la Organizaci\u00f3n para la Cooperaci\u00f3n y el Desarrollo Econ\u00f3micos (OCDE), el Consejo Internacional para la Armonizaci\u00f3n de Requisitos T\u00e9cnicos para Productos Farmac\u00e9uticos de Uso Humano (ICH) y la Agencia de Protecci\u00f3n Ambiental de EE.\u202fUU. (EPA), para obtener las versiones m\u00e1s recientes de las directrices y gu\u00edas correspondientes.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\"><strong><strong>Enfoques para la evaluaci\u00f3n de la toxicidad<\/strong><\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">La toma de decisiones regulatorias se facilita mediante el uso de toda la informaci\u00f3n relevante disponible sobre una sustancia. Una forma de evaluar toda la evidencia es utilizar un enfoque integrado de pruebas y evaluaci\u00f3n (IATA)<sup data-fn=\"52872122-9fc8-4669-a3d0-2964de330a81\" class=\"fn\"><a href=\"#52872122-9fc8-4669-a3d0-2964de330a81\" id=\"52872122-9fc8-4669-a3d0-2964de330a81-link\">1<\/a><\/sup> que considere m\u00faltiples tipos de informaci\u00f3n sobre la toxicidad de una sustancia a partir del peso de la evidencia (WoE). La informaci\u00f3n que debe tenerse en cuenta incluye datos existentes sobre la sustancia (por ejemplo, de estudios <em>in chemico<\/em>, <em>in vitro<\/em>, <em>in vivo<\/em> en humanos o <em>in vivo<\/em> en animales), las propiedades fisicoqu\u00edmicas de la sustancia, datos de enfoques sin pruebas (por ejemplo, QSAR y <em>read-across<\/em>), datos recientemente generados (de preferencia, mediante m\u00e9todos confiables y relevantes sin animales), tecnolog\u00edas \u00f3micas (por ejemplo, toxicogen\u00f3mica) y patrones de uso o escenarios de exposici\u00f3n. Los datos considerados m\u00e1s confiables, relevantes y\/o \u00fatiles para el \u00e1mbito regulatorio tienen mayor influencia en la conclusi\u00f3n de la evaluaci\u00f3n. Al evaluar los datos disponibles en conjunto, es posible realizar una evaluaci\u00f3n robusta del riesgo de una sustancia sin generar nuevos datos mediante estudios adicionales <em>in vivo<\/em> (v\u00e9ase, por ejemplo, la secci\u00f3n sobre carcinogenicidad). Adem\u00e1s, una evaluaci\u00f3n hol\u00edstica de los datos garantizar\u00e1 que no se dupliquen estudios <em>in vivo<\/em> existentes.<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-1&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-1-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-1\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-1\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-1-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Las evaluaciones mediante IATA y WoE suelen requerir juicio experto al momento de integrar los resultados de enfoques combinados para llegar a una conclusi\u00f3n fundamentada para la toma de decisiones. Los m\u00e9todos, tecnolog\u00edas y marcos que pueden incluirse en dichos enfoques son accesibles para quienes cuentan con el conocimiento tecnol\u00f3gico adecuado y existen diversos documentos de orientaci\u00f3n y estudios de caso que ayudan a desarrollar un IATA. Por ejemplo, la OCDE ha publicado directrices sobre el uso de enfoques definidos dentro de un IATA.<sup data-fn=\"72f4fd39-c1a6-4e63-8f42-cad5b9968f69\" class=\"fn\"><a href=\"#72f4fd39-c1a6-4e63-8f42-cad5b9968f69\" id=\"72f4fd39-c1a6-4e63-8f42-cad5b9968f69-link\">2<\/a><\/sup> Los enfoques definidos consisten en un procedimiento fijo de interpretaci\u00f3n de datos (por ejemplo, un modelo matem\u00e1tico o un enfoque basado en reglas) aplicado a datos generados con un conjunto definido de fuentes de informaci\u00f3n para derivar una predicci\u00f3n sin necesidad de juicio experto.<sup data-fn=\"9fd22cad-bee7-4a43-b95c-d4a05c6193c6\" class=\"fn\"><a href=\"#9fd22cad-bee7-4a43-b95c-d4a05c6193c6\" id=\"9fd22cad-bee7-4a43-b95c-d4a05c6193c6-link\">3<\/a><\/sup> En la secci\u00f3n de sensibilizaci\u00f3n cut\u00e1nea ver\u00e1s ejemplos de enfoques definidos.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Las rutas de resultados adversos (AOP) ofrecen un marco adicional para organizar los datos recopilados mediante diversos m\u00e9todos y niveles biol\u00f3gicos y evaluar las conexiones entre eventos clave y efectos adversos. A diferencia de las pruebas en animales, los m\u00e9todos sin animales reflejan la biolog\u00eda y los mecanismos de toxicidad relevantes para los humanos. Las AOP organizan eventos clave vinculados causalmente desde la exposici\u00f3n qu\u00edmica hasta un resultado adverso. Las pruebas sin animales que eval\u00faan eventos clave espec\u00edficos en una AOP permiten establecer si ocurrir\u00e1 un resultado adverso tras la exposici\u00f3n qu\u00edmica en humanos. El Programa de Desarrollo de AOP de la OCDE respalda el dise\u00f1o estructurado de las AOP y proporciona orientaci\u00f3n para su uso dentro de un IATA, tal como se describe en su Documento de Orientaci\u00f3n para el Uso de Rutas de Resultados Adversos en el Desarrollo de Enfoques Integrados de Pruebas y Evaluaci\u00f3n. Esta iniciativa promueve la aplicaci\u00f3n pr\u00e1ctica de las AOP en entornos regulatorios.<sup data-fn=\"9cf8989f-fa20-4295-85a7-73ff03bf74d5\" class=\"fn\"><a href=\"#9cf8989f-fa20-4295-85a7-73ff03bf74d5\" id=\"9cf8989f-fa20-4295-85a7-73ff03bf74d5-link\">4<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Como se mencion\u00f3 anteriormente, la consideraci\u00f3n de la exposici\u00f3n tambi\u00e9n puede formar parte de un enfoque integrado. Cuando la exposici\u00f3n humana y ambiental a una sustancia es baja o cuando las propiedades fisicoqu\u00edmicas de una sustancia determinan que ciertas v\u00edas de exposici\u00f3n no son relevantes, podr\u00eda no estar cient\u00edficamente justificado (o ser posible) realizar pruebas de toxicidad para cumplir con ciertos requisitos de informaci\u00f3n. Cuando se considera la exposici\u00f3n, el enfoque de la toma de decisiones regulatorias puede pasar de un m\u00e9todo basado en el peligro a un enfoque centrado en el riesgo que permita minimizar las pruebas en animales.<sup data-fn=\"54775efd-1607-4d58-ab28-f4c7cd33935e\" class=\"fn\"><a href=\"#54775efd-1607-4d58-ab28-f4c7cd33935e\" id=\"54775efd-1607-4d58-ab28-f4c7cd33935e-link\">5<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Sin embargo, se necesita un marco sistem\u00e1tico para evaluar la relevancia biol\u00f3gica y toxicol\u00f3gica de los m\u00e9todos individuales, considerando tambi\u00e9n diferentes escenarios de exposici\u00f3n. A fin de consolidar estos enfoques, la Cooperaci\u00f3n Internacional en Regulaci\u00f3n de Cosm\u00e9ticos (ICCR) ha establecido principios clave para integrar m\u00e9todos sin animales en una estrategia de evaluaci\u00f3n de riesgos de pr\u00f3xima generaci\u00f3n (NGRA),<sup data-fn=\"cf555ce8-47d3-4528-a249-6b7323e4458b\" class=\"fn\"><a href=\"#cf555ce8-47d3-4528-a249-6b7323e4458b\" id=\"cf555ce8-47d3-4528-a249-6b7323e4458b-link\">6<\/a><\/sup> un enfoque basado en la exposici\u00f3n y guiado por hip\u00f3tesis, que integra m\u00e9todos sin animales para garantizar que la exposici\u00f3n a sustancias qu\u00edmicas no cause da\u00f1o.<sup data-fn=\"e4a2d021-7320-4162-8b98-482cce7e6cb1\" class=\"fn\"><a href=\"#e4a2d021-7320-4162-8b98-482cce7e6cb1\" id=\"e4a2d021-7320-4162-8b98-482cce7e6cb1-link\">7<\/a><\/sup> La Asociaci\u00f3n para la Evaluaci\u00f3n de Riesgos de Sustancias Qu\u00edmicas (PARC), una iniciativa financiada por la UE para modernizar las evaluaciones de seguridad qu\u00edmica, tambi\u00e9n tiene como objetivo que la NGRA sea el enfoque predeterminado para la evaluaci\u00f3n de riesgos qu\u00edmicos en la legislaci\u00f3n europea sobre sustancias qu\u00edmicas.<sup data-fn=\"60a33ba4-b445-4dfb-866f-6677778e6023\" class=\"fn\"><a href=\"#60a33ba4-b445-4dfb-866f-6677778e6023\" id=\"60a33ba4-b445-4dfb-866f-6677778e6023-link\">8<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Adem\u00e1s de minimizar las pruebas en animales, los IATA pueden aprovechar datos y usar m\u00e9todos de alto rendimiento para evaluar un gran n\u00famero de sustancias qu\u00edmicas de manera m\u00e1s eficiente que las pruebas en animales. Los IATA tienen el potencial de transformar dram\u00e1ticamente el panorama regulatorio actual al permitir decisiones m\u00e1s relevantes para los humanos y basadas en la evaluaci\u00f3n del peligro y de la exposici\u00f3n. Asimismo, con un esfuerzo concertado entre las partes interesadas, se pueden lograr avances similares con enfoques integrados para la protecci\u00f3n ambiental.<sup data-fn=\"359bfafb-4eaa-4a7b-ac2e-567cc7cdf4f4\" class=\"fn\"><a href=\"#359bfafb-4eaa-4a7b-ac2e-567cc7cdf4f4\" id=\"359bfafb-4eaa-4a7b-ac2e-567cc7cdf4f4-link\">9<\/a><\/sup><\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\">Cosm\u00e9ticos<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">En Australia, Brasil, Canad\u00e1, Colombia, Corea del Sur, Ecuador, Guatemala, India, Suiza, Taiw\u00e1n, el Reino Unido y la UE, entre otras regiones, se ha promulgado legislaci\u00f3n que proh\u00edbe las pruebas en animales con fines cosm\u00e9ticos y\/o la venta de productos cosm\u00e9ticos que contengan ingredientes probados en animales. En otros pa\u00edses, como EE. UU., se han adoptado leyes que limitan el uso de datos de pruebas en animales a nivel estatal en lugar de a nivel nacional. Este cambio global hacia la eliminaci\u00f3n de las pruebas en animales para cosm\u00e9ticos muestra que este sector ha estado a la vanguardia en m\u00e9todos innovadores de evaluaci\u00f3n de seguridad que tienen el potencial de aplicarse de manera m\u00e1s amplia.<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-2&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-2-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-2\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-2\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-2-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Sin embargo, a pesar del car\u00e1cter innovador de estas prohibiciones, ciertos requisitos regulatorios han socavado su plena implementaci\u00f3n. Por ejemplo, las empresas pueden vender productos en la UE y el Reino Unido, incluso si han sido probados en animales en otros lugares, como China, siempre que los resultados de esas pruebas no se usen para cumplir los requisitos de las normativas cosm\u00e9ticas correspondientes. Las empresas pueden pagar por pruebas en animales exigidas en otros mercados mientras usan datos de m\u00e9todos sin animales para cumplir con las normativas de la UE o del Reino Unido. En EE. UU., aunque no existe un requisito espec\u00edfico para probar productos cosm\u00e9ticos o sus ingredientes en animales, debido a los diferentes enfoques regionales para la clasificaci\u00f3n de productos, la FDA solicita en algunos casos dichas pruebas despu\u00e9s de que los productos han sido aprobados para su comercializaci\u00f3n.<sup data-fn=\"e530a5b7-1b5d-4310-8c94-9b80a7f9be44\" class=\"fn\"><a href=\"#e530a5b7-1b5d-4310-8c94-9b80a7f9be44\" id=\"e530a5b7-1b5d-4310-8c94-9b80a7f9be44-link\">10<\/a><\/sup> Los protectores solares, por ejemplo, se regulan como cosm\u00e9ticos en la UE, pero en EE. UU. son considerados medicamentos de venta libre. La FDA ha anunciado su intenci\u00f3n de exigir que se realicen nuevas pruebas en animales para mantener en el mercado los protectores solares que contengan cualquiera de los 12 ingredientes activos espec\u00edficos indicados en una orden de 2021. No se ha hecho ninguna solicitud similar de nuevos datos sobre los mismos productos en la UE ni en otros lugares.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Tambi\u00e9n existen conflictos en algunas \u00e1reas entre la legislaci\u00f3n sobre productos qu\u00edmicos industriales y la legislaci\u00f3n espec\u00edfica para cosm\u00e9ticos. La Agencia Europea de Sustancias y Mezclas Qu\u00edmicas (ECHA), respaldada por la Comisi\u00f3n Europea, puede exigir pruebas en animales en virtud del reglamento REACH (Registro, Evaluaci\u00f3n, Autorizaci\u00f3n y Restricci\u00f3n de Sustancias Qu\u00edmicas) para evaluar la exposici\u00f3n de los trabajadores y los riesgos ambientales de las sustancias usadas exclusivamente en productos cosm\u00e9ticos. Para la evaluaci\u00f3n de sustancias utilizadas en cosm\u00e9ticos y en otros tipos de productos, los requisitos regulatorios de REACH se aplican a todos los par\u00e1metros de salud humana y ambiental, independientemente de la exposici\u00f3n de los trabajadores.<sup data-fn=\"8082f187-f858-4872-ab7a-483f156094d4\" class=\"fn\"><a href=\"#8082f187-f858-4872-ab7a-483f156094d4\" id=\"8082f187-f858-4872-ab7a-483f156094d4-link\">11<\/a><\/sup> Conflictos legislativos similares tambi\u00e9n existen en Australia y Canad\u00e1.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Dado que actualmente se usan diversos m\u00e9todos sin animales para la evaluaci\u00f3n de cosm\u00e9ticos, es posible eliminar las pruebas en animales y, al mismo tiempo, promover el rigor cient\u00edfico. Por ejemplo, la NGRA es un enfoque progresivo que implica una evaluaci\u00f3n basada en hip\u00f3tesis y guiada por la exposici\u00f3n, combinando m\u00e9todos <em>in silico<\/em>, <em>in chemico<\/em> e <em>in vitro<\/em> para permitir predicciones de riesgo m\u00e1s precisas y garantizar la confiabilidad de las evaluaciones de seguridad.<sup data-fn=\"7bb9aaed-8103-4c73-ae2a-fb64bca40077\" class=\"fn\"><a href=\"#7bb9aaed-8103-4c73-ae2a-fb64bca40077\" id=\"7bb9aaed-8103-4c73-ae2a-fb64bca40077-link\">12<\/a><\/sup><sup data-fn=\"f0b9f027-033d-4419-80e1-6f74c96dff28\" class=\"fn\"><a href=\"#f0b9f027-033d-4419-80e1-6f74c96dff28\" id=\"f0b9f027-033d-4419-80e1-6f74c96dff28-link\">13<\/a><\/sup><sup data-fn=\"bf5d49c3-17f6-40d5-9884-e822ee60d81e\" class=\"fn\"><a href=\"#bf5d49c3-17f6-40d5-9884-e822ee60d81e\" id=\"bf5d49c3-17f6-40d5-9884-e822ee60d81e-link\">14<\/a><\/sup><sup data-fn=\"34082561-b99f-40d3-8243-c71303b0cad2\" class=\"fn\"><a href=\"#34082561-b99f-40d3-8243-c71303b0cad2\" id=\"34082561-b99f-40d3-8243-c71303b0cad2-link\">15<\/a><\/sup> Los marcos NGRA pueden adaptarse para tomar decisiones sobre la seguridad de los trabajadores expuestos a productos qu\u00edmicos durante la fabricaci\u00f3n.<sup data-fn=\"3b1f1524-62f8-474c-ba88-34abb4616d04\" class=\"fn\"><a href=\"#3b1f1524-62f8-474c-ba88-34abb4616d04\" id=\"3b1f1524-62f8-474c-ba88-34abb4616d04-link\">16<\/a><\/sup> Del mismo modo, los estudios de caso de la OCDE demuestran c\u00f3mo los enfoques escalonados y flexibles de pruebas y evaluaci\u00f3n pueden usarse para abordar problemas de seguridad en diferentes escenarios regulatorios, desde la sensibilizaci\u00f3n cut\u00e1nea hasta la toxicidad sist\u00e9mica y reproductiva.<sup data-fn=\"85ba525a-51b3-4bb0-b7fb-ed025159e2f3\" class=\"fn\"><a href=\"#85ba525a-51b3-4bb0-b7fb-ed025159e2f3\" id=\"85ba525a-51b3-4bb0-b7fb-ed025159e2f3-link\">17<\/a><\/sup> La gu\u00eda del Comit\u00e9 Cient\u00edfico de Seguridad de los Consumidores (SCCS) sobre evaluaciones de seguridad cosm\u00e9tica ofrece informaci\u00f3n sobre c\u00f3mo aplicar eficazmente estos enfoques innovadores.<sup data-fn=\"cf2abac3-6c0d-4068-9952-0cd1d97aed96\" class=\"fn\"><a href=\"#cf2abac3-6c0d-4068-9952-0cd1d97aed96\" id=\"cf2abac3-6c0d-4068-9952-0cd1d97aed96-link\">18<\/a><\/sup> Adem\u00e1s, la Colaboraci\u00f3n Internacional en la Seguridad de los Cosm\u00e9ticos (ICCS), una coalici\u00f3n de empresas de cosm\u00e9ticos y cuidado personal, fabricantes de ingredientes, asociaciones comerciales y ONG,<sup data-fn=\"fdf47c61-44a4-4560-a0e2-284885ee1fd1\" class=\"fn\"><a href=\"#fdf47c61-44a4-4560-a0e2-284885ee1fd1\" id=\"fdf47c61-44a4-4560-a0e2-284885ee1fd1-link\">19<\/a><\/sup> est\u00e1 desarrollando directrices estandarizadas de buenas pr\u00e1cticas sobre el uso y la comprensi\u00f3n de las nuevas metodolog\u00edas y las NGRA para avanzar en su aceptaci\u00f3n regulatoria.<sup data-fn=\"51a1f830-0e44-4a4c-8b56-17b763758900\" class=\"fn\"><a href=\"#51a1f830-0e44-4a4c-8b56-17b763758900\" id=\"51a1f830-0e44-4a4c-8b56-17b763758900-link\">20<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">La falta de alineaci\u00f3n entre las pol\u00edticas y los avances cient\u00edficos en la evaluaci\u00f3n de cosm\u00e9ticos subraya la necesidad urgente de tomar medidas eficaces para garantizar que se usen m\u00e9todos sin animales para proteger a los consumidores, los trabajadores y el ambiente. En mayo de 2023, el gobierno del Reino Unido dio un paso significativo al suspender la emisi\u00f3n de nuevas licencias para pruebas en animales de ingredientes usados exclusivamente en cosm\u00e9ticos.<sup data-fn=\"76bc44ee-ac33-42a7-8eec-afa4fd2daafc\" class=\"fn\"><a href=\"#76bc44ee-ac33-42a7-8eec-afa4fd2daafc\" id=\"76bc44ee-ac33-42a7-8eec-afa4fd2daafc-link\">21<\/a><\/sup> Para noviembre de 2023, el Ministerio del Interior confirm\u00f3 que dichas pruebas tambi\u00e9n hab\u00edan cesado bajo todas las licencias antiguas que a\u00fan estaban vigentes.<sup data-fn=\"c4e015b2-4ff4-4443-8a90-bb9e6c246b98\" class=\"fn\"><a href=\"#c4e015b2-4ff4-4443-8a90-bb9e6c246b98\" id=\"c4e015b2-4ff4-4443-8a90-bb9e6c246b98-link\">22<\/a><\/sup> Esta medida marca el avance del Reino Unido hacia la eliminaci\u00f3n total de las pruebas en animales para cosm\u00e9ticos. Sin embargo, los ingredientes que tambi\u00e9n se usan en otros productos para el hogar contin\u00faan someti\u00e9ndose a pruebas en animales, ya que no est\u00e1n completamente exentos de este requisito.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">La transparencia total es esencial para promover decisiones informadas por parte de los consumidores, garantizar la confianza del p\u00fablico y abordar la p\u00e9rdida de efectividad de la legislaci\u00f3n y las pol\u00edticas dise\u00f1adas para asegurar que no se usen animales en la evaluaci\u00f3n de productos cosm\u00e9ticos ni de sus ingredientes para ning\u00fan fin regulatorio.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>Ecotoxicidad<\/strong><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Toxicidad acu\u00e1tica y bioacumulaci\u00f3n<\/strong><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Las pruebas de toxicidad acu\u00e1tica se realizan para medir los efectos de los productos qu\u00edmicos en el ambiente y los animales silvestres. En 2022, m\u00e1s de 122 mil peces fueron usados con fines regulatorios en la UE y Noruega.<sup data-fn=\"7e6e76fc-51d8-4488-a946-3642cf910e2c\" class=\"fn\"><a href=\"#7e6e76fc-51d8-4488-a946-3642cf910e2c\" id=\"7e6e76fc-51d8-4488-a946-3642cf910e2c-link\">23<\/a><\/sup> Dado que la evaluaci\u00f3n de la bioacumulaci\u00f3n y la toxicidad acu\u00e1tica es un requisito en diversos marcos normativos, se necesitan con urgencia estrategias para sustituir las pruebas en animales acu\u00e1ticos.<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-3&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-3-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-3\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-3\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-3-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Se ha desarrollado un prometedor ensayo de citotoxicidad con la l\u00ednea celular RTgill-W1 para estas evaluaciones,<sup data-fn=\"fea5272f-ec52-4bd5-9456-4249e6d4d937\" class=\"fn\"><a href=\"#fea5272f-ec52-4bd5-9456-4249e6d4d937\" id=\"fea5272f-ec52-4bd5-9456-4249e6d4d937-link\">24<\/a><\/sup> y la correspondiente directriz de prueba de la OCDE fue adoptada en 2021.<sup data-fn=\"e97b6ca0-3763-439d-8d98-17a4a9e5f979\" class=\"fn\"><a href=\"#e97b6ca0-3763-439d-8d98-17a4a9e5f979\" id=\"e97b6ca0-3763-439d-8d98-17a4a9e5f979-link\">25<\/a><\/sup> Este ensayo <em>in vitro<\/em> puede reducir o incluso reemplazar el uso de animales en la prueba de toxicidad aguda en peces.<sup data-fn=\"4b7eaa40-6eb5-4077-9126-0ffe6e89d3c0\" class=\"fn\"><a href=\"#4b7eaa40-6eb5-4077-9126-0ffe6e89d3c0\" id=\"4b7eaa40-6eb5-4077-9126-0ffe6e89d3c0-link\">26<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Para mejorar la predicci\u00f3n de la toxicidad aguda en peces, el proyecto 2.54 del plan de trabajo del Programa de Directrices de Prueba de la OCDE est\u00e1 elaborando un documento de orientaci\u00f3n sobre IATA para esta \u00e1rea. Este proyecto est\u00e1 copresidido por Austria y el Consejo Internacional para la Protecci\u00f3n Animal en los Programas de la OCDE (ICAPO), representado por PETA Science Consortium International.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Aunque todav\u00eda se requiere la experimentaci\u00f3n en animales, el n\u00famero usado y la necesidad de repetir estudios pueden reducirse mediante la aplicaci\u00f3n cuidadosa del Documento de Orientaci\u00f3n 23 de la OCDE sobre Pruebas de Toxicidad Acu\u00e1tica de Sustancias y Mezclas Dif\u00edciles.<sup data-fn=\"2a5a91f8-c426-4262-bf11-1731a8cfbaf4\" class=\"fn\"><a href=\"#2a5a91f8-c426-4262-bf11-1731a8cfbaf4\" id=\"2a5a91f8-c426-4262-bf11-1731a8cfbaf4-link\">27<\/a><\/sup> Este documento se actualiz\u00f3 en 2019 con informaci\u00f3n sobre enfoques para las pruebas de toxicidad acu\u00e1tica de productos qu\u00edmicos dif\u00edciles de evaluar. En esta gu\u00eda se prest\u00f3 especial atenci\u00f3n a la actualizaci\u00f3n de los m\u00e9todos disponibles para evaluar sustancias qu\u00edmicas poco solubles en agua, evitando el uso de disolventes. De este modo, se elimina la necesidad de un grupo de control con disolvente y se reduce el n\u00famero de animales usados en las pruebas. Adem\u00e1s, EE. UU. e ICAPO (representado por PETA Science Consortium International) codirigen el proyecto 2.55 del plan de trabajo del Programa de Directrices de Ensayo de la OCDE sobre el uso y an\u00e1lisis de peces de control en estudios de toxicidad. En este proyecto, se emplean an\u00e1lisis estad\u00edsticos de datos existentes y simulaciones para investigar si es posible realizar estudios de toxicidad acu\u00e1tica con un solo control cuando se usa un disolvente, reduciendo a\u00fan m\u00e1s el n\u00famero de animales explotados para este fin.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Actualmente existen varios m\u00e9todos sin animales para reducir el n\u00famero de peces usados en pruebas de bioacumulaci\u00f3n. En 2018, la OCDE adopt\u00f3 dos ensayos para la evaluaci\u00f3n de la depuraci\u00f3n intr\u00ednseca <em>in vitro<\/em> con hepatocitos de trucha arco\u00edris criopreservado<sup data-fn=\"70fbe588-a923-4a93-9b29-f221a37b242a\" class=\"fn\"><a href=\"#70fbe588-a923-4a93-9b29-f221a37b242a\" id=\"70fbe588-a923-4a93-9b29-f221a37b242a-link\">28<\/a><\/sup> y la fracci\u00f3n subcelular S9 del h\u00edgado de trucha arco\u00edris<sup data-fn=\"66dcf292-af0f-4676-b820-5983791b2fa0\" class=\"fn\"><a href=\"#66dcf292-af0f-4676-b820-5983791b2fa0\" id=\"66dcf292-af0f-4676-b820-5983791b2fa0-link\">29<\/a><\/sup> as\u00ed como su documento de orientaci\u00f3n correspondiente.<sup data-fn=\"a36b9ccf-3165-433f-8a75-c0fefbb794dc\" class=\"fn\"><a href=\"#a36b9ccf-3165-433f-8a75-c0fefbb794dc\" id=\"a36b9ccf-3165-433f-8a75-c0fefbb794dc-link\">30<\/a><\/sup> Los valores de depuraci\u00f3n intr\u00ednseca hep\u00e1tica pueden emplearse en modelos toxicocin\u00e9ticos basados en la fisiolog\u00eda para la bioacumulaci\u00f3n en peces y para la extrapolaci\u00f3n a una tasa de biotransformaci\u00f3n <em>in vivo<\/em>. Esta \u00faltima puede usarse con modelos <em>in silico<\/em> para la predicci\u00f3n de factores de bioconcentraci\u00f3n. As\u00ed, aunque estas directrices de ensayo requieren el uso de peces para obtener c\u00e9lulas primarias, pueden contribuir a sustituir el uso de peces vivos en la Prueba N.\u00ba 305 de la OCDE sobre bioacumulaci\u00f3n en peces.<sup data-fn=\"c32885d9-57b9-4d03-aa8d-380f340ea015\" class=\"fn\"><a href=\"#c32885d9-57b9-4d03-aa8d-380f340ea015\" id=\"c32885d9-57b9-4d03-aa8d-380f340ea015-link\">31<\/a><\/sup><\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Toxicidad en aves<\/strong><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">En la actualidad, la mayor\u00eda de las autoridades regulatorias exigen pruebas de toxicidad en aves para evaluar los posibles efectos ecol\u00f3gicos de las sustancias qu\u00edmicas en aves terrestres. Generalmente se requieren tres de estas pruebas para cumplir con los requisitos regulatorios: pruebas orales agudas, pruebas alimenticias y pruebas de reproducci\u00f3n. En las pruebas orales agudas y alimenticias se usan hasta 120 aves. En la prueba oral, se les administra la sustancia de manera forzada mediante una sonda durante un d\u00eda, seguida de un per\u00edodo de observaci\u00f3n de 14 d\u00edas. En la prueba alimenticia, se les da la sustancia qu\u00edmica como alimento durante cinco d\u00edas, seguida de un per\u00edodo de observaci\u00f3n de tres d\u00edas. En la prueba de reproducci\u00f3n, m\u00e1s de 120 aves adultas son alimentadas con la sustancia qu\u00edmica durante ocho a diez semanas y se asesinan varios cientos o miles de cr\u00edas para examinar posibles efectos adversos en la reproducci\u00f3n.<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-4&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-4-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-4\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-4\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-4-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">La comunidad cient\u00edfica ha expresado su preocupaci\u00f3n sobre la utilidad de las pruebas en aves para proteger a las especies terrestres. Los resultados de estas pruebas, que a menudo se realizan en dos especies, se usan para extrapolar los posibles efectos en miles de especies de aves regionales. Adem\u00e1s, la evitaci\u00f3n del alimento, la regurgitaci\u00f3n y otros problemas causados por los m\u00e9todos empleados para dosificar a las aves han dado lugar a estimaciones de toxicidad inexactas.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Para abordar estos problemas, PETA Science Consortium International colabor\u00f3 con la EPA para evaluar el uso de pruebas orales y alimenticias en aves en la toma de decisiones sobre la gesti\u00f3n de riesgos.<sup data-fn=\"829433d8-7a9b-45eb-a038-6d7d7cc10251\" class=\"fn\"><a href=\"#829433d8-7a9b-45eb-a038-6d7d7cc10251\" id=\"829433d8-7a9b-45eb-a038-6d7d7cc10251-link\">32<\/a><\/sup> La revisi\u00f3n retrospectiva examin\u00f3 20 a\u00f1os de datos de evaluaci\u00f3n de riesgos y encontr\u00f3 que la prueba alimenticia generalmente no se usa para la gesti\u00f3n de riesgos. Este estudio se utiliz\u00f3 para respaldar la pol\u00edtica de la EPA de 2020 (Gu\u00eda final para la exenci\u00f3n de pruebas alimenticias subagudas en aves para el registro de pesticidas y an\u00e1lisis retrospectivo de apoyo) que puede evitar que m\u00e1s de 700 aves sean sometidas a pruebas de toxicidad cada a\u00f1o y ahorrar recursos que se emplear\u00edan mejor en el desarrollo de m\u00e9todos sin animales adecuados para pruebas de toxicidad terrestre.<sup data-fn=\"6dd0d8eb-9d84-4e60-965a-6cdb70301dfa\" class=\"fn\"><a href=\"#6dd0d8eb-9d84-4e60-965a-6cdb70301dfa\" id=\"6dd0d8eb-9d84-4e60-965a-6cdb70301dfa-link\">33<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">PETA Science Consortium International est\u00e1 llevando a cabo una iniciativa similar para examinar el uso de dos especies en pruebas de reproducci\u00f3n aviar. Esta revisi\u00f3n retrospectiva analizar\u00e1 las diferencias en la sensibilidad de las especies de aves frente a cientos de ingredientes activos en pesticidas, con el fin de identificar tendencias sobre c\u00f3mo se usan las respuestas de toxicidad en la toma de decisiones regulatorias. La iniciativa busca identificar informaci\u00f3n que no se est\u00e1 utilizando en este proceso. Adem\u00e1s de estos proyectos, iniciativas como Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) buscan modernizar las pruebas ecol\u00f3gicas mediante m\u00e9todos computacionales predictivos que tienen el potencial de reducir las pruebas en animales terrestres y mejorar la protecci\u00f3n ecol\u00f3gica.<sup data-fn=\"bf35ee24-0173-402f-a5f4-ea92c915d0e0\" class=\"fn\"><a href=\"#bf35ee24-0173-402f-a5f4-ea92c915d0e0\" id=\"bf35ee24-0173-402f-a5f4-ea92c915d0e0-link\">34<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">La falta de armonizaci\u00f3n a nivel global resulta en un aumento de las pruebas para cumplir con requisitos regionales espec\u00edficos. Por ejemplo, la Comisi\u00f3n Europea y el Comit\u00e9 Central de Insecticidas y Registro (CIB&amp;RC) en la India exigen el uso de una sola especie para la prueba de reproducci\u00f3n aviar, mientras que la EPA en EE. UU. y la Agencia Reguladora de Manejo de Plagas de Canad\u00e1 requieren dos especies de prueba. Adem\u00e1s, la EPA permite exenciones para la prueba alimenticia aviar, y dicha prueba no es requerida por la Comisi\u00f3n Europea ni en Jap\u00f3n, pero sigue siendo obligatoria en India y China. La armonizaci\u00f3n es necesaria para eliminar a nivel mundial la exigencia de pruebas que, como se ha demostrado, no aportan informaci\u00f3n \u00fatil o que est\u00e1n afectando la calidad de la toma de decisiones regulatorias.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><strong><strong>Disrupci\u00f3n endocrina<\/strong><\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Los alteradores endocrinos (o disruptores endocrinos) son sustancias qu\u00edmicas naturales o sint\u00e9ticas que interfieren con el sistema endocrino<sup data-fn=\"c7351c66-f813-4ca6-8f78-b0cdc46df90f\" class=\"fn\"><a href=\"#c7351c66-f813-4ca6-8f78-b0cdc46df90f\" id=\"c7351c66-f813-4ca6-8f78-b0cdc46df90f-link\">35<\/a><\/sup> e influyen en diversas respuestas de las v\u00edas biol\u00f3gicas responsables de regular funciones biol\u00f3gicas fundamentales, como el crecimiento, el desarrollo, la reproducci\u00f3n, el equilibrio energ\u00e9tico, el metabolismo o la regulaci\u00f3n del peso corporal. Desde la perspectiva regulatoria de la seguridad qu\u00edmica, las v\u00edas endocrinas m\u00e1s investigadas son los sistemas de estr\u00f3genos, andr\u00f3genos, tiroides y esteroidog\u00e9nesis (EATS) y, en menor medida, los sistemas no EATS, como la v\u00eda de los retinoides.<sup data-fn=\"c53fd643-6630-4d66-a9e2-4df022dbd465\" class=\"fn\"><a href=\"#c53fd643-6630-4d66-a9e2-4df022dbd465\" id=\"c53fd643-6630-4d66-a9e2-4df022dbd465-link\">36<\/a><\/sup><\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-5&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-5-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-5\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-5\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-5-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Se sabe mucho sobre los complejos mecanismos mediante los cuales las sustancias qu\u00edmicas pueden interferir con las v\u00edas endocrinas en humanos<sup data-fn=\"2cf689fb-1e04-4e9d-9b68-92ec88607d75\" class=\"fn\"><a href=\"#2cf689fb-1e04-4e9d-9b68-92ec88607d75\" id=\"2cf689fb-1e04-4e9d-9b68-92ec88607d75-link\">37<\/a><\/sup> y animales silvestres.<sup data-fn=\"d02bf635-09b8-44b1-8fb9-1d45a97e4db7\" class=\"fn\"><a href=\"#d02bf635-09b8-44b1-8fb9-1d45a97e4db7\" id=\"d02bf635-09b8-44b1-8fb9-1d45a97e4db7-link\">38<\/a><\/sup> Numerosas AOP\u00a0 relacionadas con la disrupci\u00f3n endocrina est\u00e1n incluidas en el AOP Wiki,<sup data-fn=\"a7001ea1-3080-4ee3-86c3-002f70f6365b\" class=\"fn\"><a href=\"#a7001ea1-3080-4ee3-86c3-002f70f6365b\" id=\"a7001ea1-3080-4ee3-86c3-002f70f6365b-link\">39<\/a><\/sup> y la OCDE ha publicado varios estudios de caso sobre IATAs.<sup data-fn=\"993a6913-6ddd-4f17-b3ab-93ee6bb3b3b7\" class=\"fn\"><a href=\"#993a6913-6ddd-4f17-b3ab-93ee6bb3b3b7\" id=\"993a6913-6ddd-4f17-b3ab-93ee6bb3b3b7-link\">40<\/a><\/sup> Las pruebas <em>in vivo<\/em> para evaluar la disrupci\u00f3n endocrina presentan una alta variabilidad (por ejemplo, el estr\u00e9s que experimenta un animal puede influir significativamente en el resultado del estudio) y baja sensibilidad, por lo que es poco probable que detecten eventos relevantes de disrupci\u00f3n endocrina.<sup data-fn=\"ee878536-fa04-437f-a4df-d459745c6f8b\" class=\"fn\"><a href=\"#ee878536-fa04-437f-a4df-d459745c6f8b\" id=\"ee878536-fa04-437f-a4df-d459745c6f8b-link\">41<\/a><\/sup> Los estudios cl\u00e1sicos basados en par\u00e1metros finales no son apropiados en esta \u00e1rea y deben ser reemplazados por estudios <em>in vitro<\/em>, en los cuales los m\u00faltiples factores que podr\u00edan afectar los resultados pueden controlarse de manera m\u00e1s eficaz.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Entre 2019 y 2024, ocho proyectos bajo el European Cluster to Improve Identification of Endocrine Disruptors (EURION), con una financiaci\u00f3n de 50 millones de euros por parte de la Comisi\u00f3n Europea, se centraron en el desarrollo de herramientas destinadas a mejorar la evaluaci\u00f3n regulatoria de los efectos relacionados con el sistema endocrino (alteraci\u00f3n del sistema de hormonas tiroideas, trastornos metab\u00f3licos, neurotoxicidad del desarrollo y fertilidad femenina) y en reducir la dependencia de las pruebas en animales. Un reporte sobre el proyecto EURION concluy\u00f3 que se necesita apoyo para una implementaci\u00f3n m\u00e1s r\u00e1pida de los hallazgos cient\u00edficos en m\u00e9todos de prueba, as\u00ed como para la actualizaci\u00f3n de los requisitos de prueba en las normativas qu\u00edmicas con el fin de incluir los ensayos desarrollados recientemente.<sup data-fn=\"a5c95b1c-b0da-4819-967c-29d6f1c0e030\" class=\"fn\"><a href=\"#a5c95b1c-b0da-4819-967c-29d6f1c0e030\" id=\"a5c95b1c-b0da-4819-967c-29d6f1c0e030-link\">42<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">La Oficina de Investigaci\u00f3n y Desarrollo (ORD) de la EPA est\u00e1 desarrollando ensayos <em>in silico<\/em> e <em>in vitro<\/em>, as\u00ed como AOP, para evaluar de manera robusta los efectos de sustancias qu\u00edmicas sobre el sistema endocrino. Por ejemplo, el Toxicity Forecaster (ToxCast) de la EPA clasifica y prioriza sustancias qu\u00edmicas usando m\u00e1s de 700 ensayos de cribado de alto rendimiento y toxicolog\u00eda computacional que abarcan una variedad de respuestas celulares relevantes y v\u00edas de se\u00f1alizaci\u00f3n.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Tras un estudio comparativo de los resultados de los ensayos de la v\u00eda del estr\u00f3geno en ToxCast y en el ensayo uterotr\u00f3fico,<sup data-fn=\"4043fc9d-1f0c-4841-a1bd-9fe0ccb96c6d\" class=\"fn\"><a href=\"#4043fc9d-1f0c-4841-a1bd-9fe0ccb96c6d\" id=\"4043fc9d-1f0c-4841-a1bd-9fe0ccb96c6d-link\">43<\/a><\/sup> la EPA anunci\u00f3 que aceptar\u00e1 los datos del Modelo de Bioactividad ER de ToxCast como alternativa a al menos una prueba en animales,<sup data-fn=\"e92ad3bd-9da8-4acf-b266-a153bd127137\" class=\"fn\"><a href=\"#e92ad3bd-9da8-4acf-b266-a153bd127137\" id=\"e92ad3bd-9da8-4acf-b266-a153bd127137-link\">44<\/a><\/sup><sup data-fn=\"2f691520-0772-44d7-80d3-23be818e05cf\" class=\"fn\"><a href=\"#2f691520-0772-44d7-80d3-23be818e05cf\" id=\"2f691520-0772-44d7-80d3-23be818e05cf-link\">45<\/a><\/sup> el ensayo uterotr\u00f3fico, que eval\u00faa los efectos sobre la v\u00eda del estr\u00f3geno.<sup data-fn=\"21797ab5-f298-4dcc-898b-650ad3c09852\" class=\"fn\"><a href=\"#21797ab5-f298-4dcc-898b-650ad3c09852\" id=\"21797ab5-f298-4dcc-898b-650ad3c09852-link\">46<\/a><\/sup> En la UE, el Modelo de Bioactividad ER de ToxCast se acepta actualmente como fuente de informaci\u00f3n <em>in vitro <\/em>sobre el mecanismo de acci\u00f3n. Esta informaci\u00f3n es requerida como parte de la identificaci\u00f3n de sustancias como disruptores endocrinos en el marco regulatorio vigente para biocidas y productos fitosanitarios.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">En colaboraci\u00f3n con otras organizaciones, el Centro Com\u00fan de Investigaci\u00f3n de la UE y la EPA ORD est\u00e1n desarrollando conjuntos de ensayos relevantes basados en el AOP de la tiroides y evaluando su validez.<sup data-fn=\"f80636c9-b1fc-44fe-ab4b-006d31e076d2\" class=\"fn\"><a href=\"#f80636c9-b1fc-44fe-ab4b-006d31e076d2\" id=\"f80636c9-b1fc-44fe-ab4b-006d31e076d2-link\">47<\/a><\/sup> En 2024, la OCDE incorpor\u00f3 a su plan de trabajo para el desarrollo de directrices dos de estos ensayos dirigidos a diferentes eventos moleculares desencadenantes de la disrupci\u00f3n de la v\u00eda tiroidea.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><strong><strong>Irritaci\u00f3n\/corrosi\u00f3n ocular<\/strong><\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Para evaluar la irritaci\u00f3n y la corrosi\u00f3n ocular mediante la prueba de Draize, se aplica una sustancia qu\u00edmica en los ojos de los conejos y se monitorea el grado de da\u00f1o durante 14 d\u00edas. Los conejos pueden sufrir inflamaci\u00f3n ocular, secreci\u00f3n, ulceraci\u00f3n, hemorragias, opacidad o ceguera. La prueba de Draize se desarroll\u00f3 en 1944 y, desde entonces, se han creado m\u00e9todos de reemplazo avanzados que han demostrado ser igual de o m\u00e1s confiables que la prueba en conejos. Por ejemplo, un an\u00e1lisis de 491 sustancias qu\u00edmicas con al menos dos pruebas oculares en conejos mostr\u00f3 que la probabilidad de obtener la misma clasificaci\u00f3n del Sistema Globalmente Armonizado de Clasificaci\u00f3n y Etiquetado de Productos Qu\u00edmicos (GHS) m\u00e1s de una vez fue del 73% para la categor\u00eda GHS 1 (causa da\u00f1o ocular grave), 32,9% para la categor\u00eda GHS 2A (irritante), 15,5% para la categor\u00eda GHS 2B (irritante leve) y 93,9% para ninguna categor\u00eda (no irritante).<sup data-fn=\"df748f7c-6df9-480c-9a53-4cae4e9d9d4e\" class=\"fn\"><a href=\"#df748f7c-6df9-480c-9a53-4cae4e9d9d4e\" id=\"df748f7c-6df9-480c-9a53-4cae4e9d9d4e-link\">48<\/a><\/sup> Es importante destacar que estos resultados mostraron que exist\u00eda una probabilidad del 10,4% de que una sustancia identificada inicialmente como causante de da\u00f1o irreversible grave (categor\u00eda 1) fuera clasificada despu\u00e9s como no irritante (sin categor\u00eda).<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-6&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-6-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-6\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-6\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-6-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Existen m\u00e9todos robustos sin animales que pueden reemplazar completamente la prueba de Draize sin necesidad de juicio experto ni de una evaluaci\u00f3n basada en el WoE:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Prueba de la OCDE Nro. 492B: Ensayo con epitelio humano reconstruido similar a la c\u00f3rnea (RhCE) para la identificaci\u00f3n de peligros oculares.<\/strong> Puede usarse para identificar sustancias qu\u00edmicas que no requieren clasificaci\u00f3n (GHS sin categor\u00eda) y aquellas que requieren clasificaci\u00f3n por irritaci\u00f3n ocular (categor\u00eda 2 del GHS) y por da\u00f1o ocular grave (categor\u00eda 1 del GHS).<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 467: Enfoques definidos para da\u00f1o ocular grave e irritaci\u00f3n ocular.<\/strong> Los enfoques de esta prueba se basan en:\n<ul class=\"wp-block-list\">\n<li>Propiedades fisicoqu\u00edmicas y datos <em>in vitro<\/em> de la <strong>Prueba de la OCDE Nro. 492<\/strong> (ensayo con epitelio humano reconstruido similar a la c\u00f3rnea, RhCE) y la <strong>Prueba de la OCDE Nro. 437<\/strong> (m\u00e9todo de opacidad y permeabilidad corneal bovina, BCOP) para l\u00edquidos puros no tensioactivos.<\/li>\n\n\n\n<li>Datos <em>in vitro<\/em> de la <strong>Prueba de la OCDE Nro. 491<\/strong> (ensayo <em>in vitro<\/em> de exposici\u00f3n corta, STE) y la <strong>Prueba de la OCDE Nro. 437<\/strong> para l\u00edquidos puros y\/o diluidos no tensioactivos o s\u00f3lidos disueltos en agua.<\/li>\n\n\n\n<li>Datos <em>in vitro<\/em> de la <strong>Prueba de la OCDE Nro. 437<\/strong> y la <strong>Prueba de la OCDE Nro. 492<\/strong> para s\u00f3lidos puros.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Los enfoques definidos pueden usarse para identificar sustancias qu\u00edmicas que no requieren clasificaci\u00f3n (GHS sin categor\u00eda) y aquellas que requieren clasificaci\u00f3n por irritaci\u00f3n ocular (categor\u00eda 2 del GHS) y por da\u00f1o ocular grave (categor\u00eda 1 del GHS).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Como se describe en la gu\u00eda de la OCDE sobre un IATA de da\u00f1o ocular grave e irritaci\u00f3n,<sup data-fn=\"c1d1fff4-4333-4eb8-92f0-c31a6760bcd6\" class=\"fn\"><a href=\"#c1d1fff4-4333-4eb8-92f0-c31a6760bcd6\" id=\"c1d1fff4-4333-4eb8-92f0-c31a6760bcd6-link\">49<\/a><\/sup> otros m\u00e9todos <em>in vitro<\/em> pueden combinarse para reemplazar completamente la prueba de Draize:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Prueba de la OCDE Nro. 494:<\/strong> <strong>Ensayo Vitrigel-Eye para irritaci\u00f3n ocular.<\/strong> Puede usarse para identificar sustancias qu\u00edmicas que no se clasifican por irritaci\u00f3n ocular ni da\u00f1o ocular grave (GHS sin categor\u00eda).<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 496:<\/strong> <strong>Ensayo macromolecular <em>in vitro<\/em>. <\/strong>Puede usarse para identificar sustancias qu\u00edmicas que causan da\u00f1o ocular grave (categor\u00eda 1 del GHS) y\/o que no requieren clasificaci\u00f3n.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 460:<\/strong> <strong>Ensayo de fuga de fluoresce\u00edna.<\/strong> Puede usarse para identificar sustancias qu\u00edmicas que causan da\u00f1o ocular grave (categor\u00eda 1 del GHS). Se recomienda como paso inicial en un enfoque descendente (<em>top-down<\/em>) para identificar corrosivos o irritantes severos.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 438:<\/strong> <strong>Ensayo con ojo de pollo aislado.<\/strong> Puede usarse para identificar sustancias qu\u00edmicas que causan da\u00f1o ocular grave (categor\u00eda 1 del GHS) o que no requieren clasificaci\u00f3n. Se recomienda como primer paso dentro de una estrategia de ensayo descendente (<em>top-down<\/em>) o ascendente (<em>bottom-up<\/em>).<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Estos m\u00e9todos est\u00e1n generalmente validados para su uso con cosm\u00e9ticos y productos qu\u00edmicos industriales. Algunos m\u00e9todos ser\u00e1n m\u00e1s apropiados que otros, dependiendo del dominio de aplicabilidad del m\u00e9todo, del prop\u00f3sito de la prueba y del tipo de sustancia qu\u00edmica (por ejemplo, tensioactivos o s\u00f3lidos).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">La EPA actualmente acepta el uso de m\u00e9todos <em>in vitro<\/em> y <em>ex vivo<\/em> para determinar la irritaci\u00f3n y la corrosi\u00f3n ocular al clasificar productos qu\u00edmicos industriales, productos de limpieza antimicrobianos y, previa evaluaci\u00f3n, otros productos pesticidas. La Oficina de Prevenci\u00f3n de la Contaminaci\u00f3n y Sustancias T\u00f3xicas de la EPA public\u00f3 en 2024 una gu\u00eda que desaconseja las pruebas prospectivas de Draize para nuevos productos qu\u00edmicos,<sup data-fn=\"6441dcb3-731a-4e24-a0eb-4e3d44aef72e\" class=\"fn\"><a href=\"#6441dcb3-731a-4e24-a0eb-4e3d44aef72e\" id=\"6441dcb3-731a-4e24-a0eb-4e3d44aef72e-link\">50<\/a><\/sup> y en 2015, la Oficina de Programas de Pesticidas (OPP) public\u00f3 una gu\u00eda que describe las pruebas que la industria puede usar para este par\u00e1metro.<sup data-fn=\"c2b7dfa1-3ead-463e-a6de-0d275aa53eb0\" class=\"fn\"><a href=\"#c2b7dfa1-3ead-463e-a6de-0d275aa53eb0\" id=\"c2b7dfa1-3ead-463e-a6de-0d275aa53eb0-link\">51<\/a><\/sup> OPP tambi\u00e9n public\u00f3 en su p\u00e1gina web<sup data-fn=\"ab57d837-cc20-4efc-9e48-1da410a7e1ae\" class=\"fn\"><a href=\"#ab57d837-cc20-4efc-9e48-1da410a7e1ae\" id=\"ab57d837-cc20-4efc-9e48-1da410a7e1ae-link\">52<\/a><\/sup> un art\u00edculo \u2013escrito por PETA Science Consortium International y NICEATM, entre otros\u2013 que propone \u00a0enfoques definidos que combinan m\u00e9todos <em>in vitro<\/em> y <em>ex vivo<\/em> para evaluar el potencial de irritaci\u00f3n y corrosi\u00f3n ocular de formulaciones agroqu\u00edmicas.<sup data-fn=\"f021ead7-2d04-4b33-9e98-c0642f2eb7e2\" class=\"fn\"><a href=\"#f021ead7-2d04-4b33-9e98-c0642f2eb7e2\" id=\"f021ead7-2d04-4b33-9e98-c0642f2eb7e2-link\">53<\/a><\/sup><\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><strong><strong>Genotoxicidad y carcinogenicidad<\/strong><\/strong><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><strong><strong>Genotoxicidad<\/strong><\/strong><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Los principales par\u00e1metros de genotoxicidad que deben evaluarse con fines regulatorios son la mutaci\u00f3n g\u00e9nica, las aberraciones cromos\u00f3micas estructurales (clastogenicidad) y las aberraciones cromos\u00f3micas num\u00e9ricas (aneuploid\u00eda). Las gu\u00edas de la OCDE para evaluar la genotoxicidad <em>in vitro<\/em> cubren uno o dos par\u00e1metros simult\u00e1neamente:<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-7&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-7-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-7\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-7\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-7-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<ul class=\"wp-block-list\">\n<li><strong>Prueba de la OCDE Nro. 471: Ensayo de mutaci\u00f3n inversa en bacterias.<\/strong> Conocido como prueba de Ames, este ensayo usa <em>Salmonella typhimurium<\/em> y <em>Escherichia coli<\/em>, que requieren amino\u00e1cidos, para detectar mutaciones puntuales por sustituciones de bases o desplazamientos del marco de lectura (<em>frameshifts<\/em>).<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 487: Ensayo <em>in vitro<\/em> de micron\u00facleos.<\/strong> Puede usarse para detectar micron\u00facleos en el citoplasma de c\u00e9lulas en interfase que han experimentado divisi\u00f3n celular durante o despu\u00e9s de la exposici\u00f3n a una sustancia de prueba. Este ensayo detecta aberraciones cromos\u00f3micas estructurales y num\u00e9ricas.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 490: Ensayos <em>in vitro<\/em> de mutaci\u00f3n g\u00e9nica en c\u00e9lulas de mam\u00edfero usando el gen de la quinasa de la timidina.<\/strong> Se pueden usar dos ensayos distintos para detectar mutaciones g\u00e9nicas inducidas por sustancias qu\u00edmicas.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 473: Ensayo <em>in vitro<\/em> de aberraciones cromos\u00f3micas en c\u00e9lulas de mam\u00edfero.<\/strong> Este ensayo identifica sustancias qu\u00edmicas que causan aberraciones cromos\u00f3micas estructurales.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 476: Ensayo <em>in vitro<\/em> de mutaci\u00f3n g\u00e9nica en c\u00e9lulas de mam\u00edfero usando los genes Hrpt y xrpt.<\/strong> Estos ensayos pueden detectar mutaciones g\u00e9nicas inducidas por sustancias qu\u00edmicas.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">La evaluaci\u00f3n de la genotoxicidad para fines regulatorios generalmente se realiza en etapas, comenzando con una bater\u00eda b\u00e1sica de pruebas <em>in vitro<\/em> (por ejemplo, las pruebas de Ames, micron\u00facleos y aberraciones cromos\u00f3micas). La necesidad de complementar las pruebas <em>in vitro<\/em> con pruebas <em>in vivo<\/em> depende de los resultados y de los requisitos regulatorios. Por ejemplo, en el caso de las normativas de la UE sobre productos qu\u00edmicos industriales y biocidas, un resultado positivo en cualquiera de las pruebas <em>in vitro<\/em> requeridas debe ser seguido por una prueba <em>in vivo<\/em>.<sup data-fn=\"98ac2cc4-e458-431a-ad41-a90dca123a6d\" class=\"fn\"><a href=\"#98ac2cc4-e458-431a-ad41-a90dca123a6d\" id=\"98ac2cc4-e458-431a-ad41-a90dca123a6d-link\">54<\/a><\/sup><sup data-fn=\"bf060dee-83fe-46aa-a00d-cab56807d10a\" class=\"fn\"><a href=\"#bf060dee-83fe-46aa-a00d-cab56807d10a\" id=\"bf060dee-83fe-46aa-a00d-cab56807d10a-link\">55<\/a><\/sup> Sin embargo, si una sustancia produce resultados negativos en las pruebas <em>in vitro<\/em>, puede clasificarse como sin potencial genot\u00f3xico y no se requerir\u00edan m\u00e1s pruebas de genotoxicidad. Por el contrario, para algunas clases de productos qu\u00edmicos, se exigen pruebas <em>in vivo<\/em> independientemente de los resultados de las pruebas <em>in vitro<\/em> (por ejemplo, productos fitosanitarios y productos farmac\u00e9uticos).<sup data-fn=\"ee41821b-d205-426d-a1de-249de30fb214\" class=\"fn\"><a href=\"#ee41821b-d205-426d-a1de-249de30fb214\" id=\"ee41821b-d205-426d-a1de-249de30fb214-link\">56<\/a><\/sup><sup data-fn=\"8923d8ae-d2dc-4d0a-ae02-b12e4ba49c17\" class=\"fn\"><a href=\"#8923d8ae-d2dc-4d0a-ae02-b12e4ba49c17\" id=\"8923d8ae-d2dc-4d0a-ae02-b12e4ba49c17-link\">57<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Se puede reducir la necesidad de realizar pruebas <em>in vivo<\/em> si se cuenta con datos apropiados provenientes de estudios <em>in silico<\/em> (por ejemplo, QSAR y <em>read-across<\/em>). Por ejemplo, la base de datos consolidada sobre genotoxicidad y carcinogenicidad de EURL ECVAM, publicada en la colecci\u00f3n EURL ECVAM del cat\u00e1logo de datos del Centro Com\u00fan de Investigaci\u00f3n (JRC), proporciona recursos sustanciales para <em>read-across<\/em>.<sup data-fn=\"510e6be3-767a-41cd-94d0-a3d5a5db75bd\" class=\"fn\"><a href=\"#510e6be3-767a-41cd-94d0-a3d5a5db75bd\" id=\"510e6be3-767a-41cd-94d0-a3d5a5db75bd-link\">58<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Adem\u00e1s, los m\u00e9todos avanzados <em>in vitro<\/em> pueden ofrecer opciones de seguimiento y reducci\u00f3n de riesgos para su uso en un enfoque basado en el WoE. Por ejemplo, el biomarcador transcript\u00f3mico <em>in vitro<\/em> sensible a agentes que inducen da\u00f1o en el ADN (DDI), el TGx-DDI,<sup data-fn=\"925ae4a6-27ff-46bb-b341-aac6e8617fd6\" class=\"fn\"><a href=\"#925ae4a6-27ff-46bb-b341-aac6e8617fd6\" id=\"925ae4a6-27ff-46bb-b341-aac6e8617fd6-link\">59<\/a><\/sup><sup data-fn=\"6895fce3-3aff-4fc2-af7d-4dd69c349172\" class=\"fn\"><a href=\"#6895fce3-3aff-4fc2-af7d-4dd69c349172\" id=\"6895fce3-3aff-4fc2-af7d-4dd69c349172-link\">60<\/a><\/sup> y el ensayo ToxTracker<sup data-fn=\"5ac3a73f-2d2a-450b-b6a5-920fa99211e1\" class=\"fn\"><a href=\"#5ac3a73f-2d2a-450b-b6a5-920fa99211e1\" id=\"5ac3a73f-2d2a-450b-b6a5-920fa99211e1-link\">61<\/a><\/sup><sup data-fn=\"90f339a9-041d-4b30-854e-1a204ca43893\" class=\"fn\"><a href=\"#90f339a9-041d-4b30-854e-1a204ca43893\" id=\"90f339a9-041d-4b30-854e-1a204ca43893-link\">62<\/a><\/sup><sup data-fn=\"e57da551-43e9-463a-89b4-f6b37f0f5a50\" class=\"fn\"><a href=\"#e57da551-43e9-463a-89b4-f6b37f0f5a50\" id=\"e57da551-43e9-463a-89b4-f6b37f0f5a50-link\">63<\/a><\/sup> pueden proporcionar informaci\u00f3n sobre el modo de acci\u00f3n de posibles genot\u00f3xicos y han sido presentados en programas regulatorios formales de \u201ccalificaci\u00f3n\u201d.<sup data-fn=\"b4824e8d-b847-470a-a34a-76eedcc05288\" class=\"fn\"><a href=\"#b4824e8d-b847-470a-a34a-76eedcc05288\" id=\"b4824e8d-b847-470a-a34a-76eedcc05288-link\">64<\/a><\/sup><sup data-fn=\"24a5a193-eba5-4421-855a-b6c375cc4654\" class=\"fn\"><a href=\"#24a5a193-eba5-4421-855a-b6c375cc4654\" id=\"24a5a193-eba5-4421-855a-b6c375cc4654-link\">65<\/a><\/sup> Los datos generados mediante el ensayo ToxTracker y <em>read-across<\/em> se han usado en los expedientes REACH de la UE.<sup data-fn=\"e48e31df-7d8c-41db-9487-b8ab39b2b670\" class=\"fn\"><a href=\"#e48e31df-7d8c-41db-9487-b8ab39b2b670\" id=\"e48e31df-7d8c-41db-9487-b8ab39b2b670-link\">66<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Los ensayos de micron\u00facleos y de cometa en piel tridimensional reconstruida son m\u00e9todos adicionales sin animales que pueden usarse para dar seguimiento a resultados positivos de los ensayos est\u00e1ndar de genotoxicidad <em>in vitro<\/em> en compuestos administrados por v\u00eda d\u00e9rmica. Estos m\u00e9todos representan una oportunidad importante para evitar el uso de animales en las pruebas de genotoxicidad.<sup data-fn=\"d3f7ef5f-778c-4330-a9e3-18786355801c\" class=\"fn\"><a href=\"#d3f7ef5f-778c-4330-a9e3-18786355801c\" id=\"d3f7ef5f-778c-4330-a9e3-18786355801c-link\">67<\/a><\/sup> Los requisitos de informaci\u00f3n para la evaluaci\u00f3n de genotoxicidad de cosm\u00e9ticos<sup data-fn=\"c4286d1b-7553-4715-8b6d-09a9802c47af\" class=\"fn\"><a href=\"#c4286d1b-7553-4715-8b6d-09a9802c47af\" id=\"c4286d1b-7553-4715-8b6d-09a9802c47af-link\">68<\/a><\/sup> ya pueden incluir la prueba de micron\u00facleos o de cometa usando piel humana tridimensional reconstruida. Para esta \u00faltima prueba tambi\u00e9n se pueden usar c\u00e9lulas de mam\u00edfero. El r\u00e1pido progreso en el desarrollo de modelos tridimensionales de h\u00edgado y v\u00edas respiratorias ofrece la posibilidad de que en un futuro cercano no se usen animales en la evaluaci\u00f3n del potencial genot\u00f3xico de compuestos administrados por v\u00eda oral o inhalatoria.<sup data-fn=\"a13f57e0-ae1c-4a2c-be04-d2f3df1bfe72\" class=\"fn\"><a href=\"#a13f57e0-ae1c-4a2c-be04-d2f3df1bfe72\" id=\"a13f57e0-ae1c-4a2c-be04-d2f3df1bfe72-link\">69<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Los m\u00e9todos sin animales est\u00e1n ganando terreno a nivel internacional. Generar datos completos basados en estos m\u00e9todos y desarrollar estudios de caso, como el de la cumarina usada en productos cosm\u00e9ticos, es un componente importante para respaldar la adopci\u00f3n de la evaluaci\u00f3n de riesgos de pr\u00f3xima generaci\u00f3n.<sup data-fn=\"5dda1125-b5e6-43c8-8c0d-d1b44e9ddc7e\" class=\"fn\"><a href=\"#5dda1125-b5e6-43c8-8c0d-d1b44e9ddc7e\" id=\"5dda1125-b5e6-43c8-8c0d-d1b44e9ddc7e-link\">70<\/a><\/sup><sup data-fn=\"06e57241-8f9f-4f1c-b3a9-7e17aafcadc3\" class=\"fn\"><a href=\"#06e57241-8f9f-4f1c-b3a9-7e17aafcadc3\" id=\"06e57241-8f9f-4f1c-b3a9-7e17aafcadc3-link\">71<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Los estudios de caso IATA sobre genotoxicidad<sup data-fn=\"ec483e91-03d4-4f13-aa63-fbc0a9a4d379\" class=\"fn\"><a href=\"#ec483e91-03d4-4f13-aa63-fbc0a9a4d379\" id=\"ec483e91-03d4-4f13-aa63-fbc0a9a4d379-link\">72<\/a><\/sup> y mutagenicidad<sup data-fn=\"4f4f8b5c-6041-486a-9928-e60d10779a11\" class=\"fn\"><a href=\"#4f4f8b5c-6041-486a-9928-e60d10779a11\" id=\"4f4f8b5c-6041-486a-9928-e60d10779a11-link\">73<\/a><\/sup> de la OCDE<sup data-fn=\"b232c395-f616-47a9-8af3-a51e528b9939\" class=\"fn\"><a href=\"#b232c395-f616-47a9-8af3-a51e528b9939\" id=\"b232c395-f616-47a9-8af3-a51e528b9939-link\">74<\/a><\/sup> ilustran enfoques viables para desarrollar directrices adecuadas de evaluaci\u00f3n de la seguridad para determinar el riesgo de genotoxicidad sist\u00e9mica sin pruebas en animales.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h3 class=\"wp-block-heading\"><strong><strong>Carcinogenicidad<\/strong><\/strong><a id=\"_msocom_1\"><\/a><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">La evaluaci\u00f3n de la carcinogenicidad a menudo requiere realizar pruebas en ratas y\/o ratones durante la mayor parte de su vida (hasta dos a\u00f1os). La prueba requiere un m\u00ednimo de 400 ratas y\/o ratones por cada evaluaci\u00f3n qu\u00edmica (Pruebas de la OCDE Nro. 451, 452 y 453).<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-8&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-8-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-8\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-8\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-8-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Aunque los estudios de carcinogenicidad en animales todav\u00eda se realizan de manera rutinaria, la prueba ha estado bajo escrutinio cient\u00edfico desde principios de la d\u00e9cada de 1970 por su falta de reproducibilidad<sup data-fn=\"13e78d9b-3eb7-4233-8ae2-78dc51cec9eb\" class=\"fn\"><a href=\"#13e78d9b-3eb7-4233-8ae2-78dc51cec9eb\" id=\"13e78d9b-3eb7-4233-8ae2-78dc51cec9eb-link\">75<\/a><\/sup> y su incapacidad para predecir resultados en humanos.<sup data-fn=\"7fe9cb03-e9bf-4f5f-a2f8-5041dcc3f313\" class=\"fn\"><a href=\"#7fe9cb03-e9bf-4f5f-a2f8-5041dcc3f313\" id=\"7fe9cb03-e9bf-4f5f-a2f8-5041dcc3f313-link\">76<\/a><\/sup> Cabe destacar que existen dos supuestos err\u00f3neos que subyacen a estos bioensayos: (1) los carcin\u00f3genos en roedores son carcin\u00f3genos en humanos, y (2) la exposici\u00f3n a dosis altas en roedores indica una dosis ambientalmente relevante. Los datos de carcinogenicidad producidos en los \u00faltimos 50 a\u00f1os han demostrado que ambos supuestos son incorrectos. D\u00e9cadas de revisiones cient\u00edficas resaltan la falta general de confiabilidad de los bioensayos de c\u00e1ncer en roedores para predecir c\u00e1ncer en humanos.<sup data-fn=\"122cd799-8240-41fc-954a-055c834f2c69\" class=\"fn\"><a href=\"#122cd799-8240-41fc-954a-055c834f2c69\" id=\"122cd799-8240-41fc-954a-055c834f2c69-link\">77<\/a><\/sup><sup data-fn=\"bd9e09d2-77f9-45d1-937c-881251881614\" class=\"fn\"><a href=\"#bd9e09d2-77f9-45d1-937c-881251881614\" id=\"bd9e09d2-77f9-45d1-937c-881251881614-link\">78<\/a><\/sup><sup data-fn=\"72c70e96-37b0-49e6-aeb3-215292b3061b\" class=\"fn\"><a href=\"#72c70e96-37b0-49e6-aeb3-215292b3061b\" id=\"72c70e96-37b0-49e6-aeb3-215292b3061b-link\">79<\/a><\/sup><sup data-fn=\"bdba0109-1f5f-411b-92c6-7cfb4686eea6\" class=\"fn\"><a href=\"#bdba0109-1f5f-411b-92c6-7cfb4686eea6\" id=\"bdba0109-1f5f-411b-92c6-7cfb4686eea6-link\">80<\/a><\/sup><sup data-fn=\"fa306f3d-a970-4a7a-ac84-d8e312b42306\" class=\"fn\"><a href=\"#fa306f3d-a970-4a7a-ac84-d8e312b42306\" id=\"fa306f3d-a970-4a7a-ac84-d8e312b42306-link\">81<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Por ejemplo, un programa de la UE evalu\u00f3 202 revisiones de plaguicidas y demostr\u00f3 que el estudio de carcinogenicidad en ratones aport\u00f3 poco o nada a la determinaci\u00f3n de una ingesta diaria aceptable para la evaluaci\u00f3n del riesgo cr\u00f3nico en humanos y la clasificaci\u00f3n de peligros con fines de etiquetado.<sup data-fn=\"35bbd878-abc4-4368-91f3-a0f6a493e1ca\" class=\"fn\"><a href=\"#35bbd878-abc4-4368-91f3-a0f6a493e1ca\" id=\"35bbd878-abc4-4368-91f3-a0f6a493e1ca-link\">82<\/a><\/sup> En cuanto a las aprobaciones de plaguicidas, los autores mostraron que el estudio en ratones no influy\u00f3 en ning\u00fan resultado. Un estudio adicional se\u00f1al\u00f3 que los datos recopilados de 182 sustancias farmac\u00e9uticas muestran que se obtiene poco valor del estudio de carcinogenicidad cuando los compuestos carecen de ciertos factores de riesgo histopatol\u00f3gicos, alteraciones hormonales y resultados positivos en pruebas de toxicidad gen\u00e9tica.<sup data-fn=\"16b9e7b0-ec66-4703-9eea-125d362d3605\" class=\"fn\"><a href=\"#16b9e7b0-ec66-4703-9eea-125d362d3605\" id=\"16b9e7b0-ec66-4703-9eea-125d362d3605-link\">83<\/a><\/sup> Este estudio se us\u00f3 para respaldar un grupo internacional que desarroll\u00f3 un enfoque basado en WoE para cumplir algunos de los requisitos de la prueba de carcinogenicidad sin el ensayo de dos a\u00f1os en ratas.<sup data-fn=\"fd1c25b9-33c1-479a-9ee0-600332682d5e\" class=\"fn\"><a href=\"#fd1c25b9-33c1-479a-9ee0-600332682d5e\" id=\"fd1c25b9-33c1-479a-9ee0-600332682d5e-link\">84<\/a><\/sup><sup data-fn=\"309ae815-c9ca-4a85-89b3-470ceecda3d5\" class=\"fn\"><a href=\"#309ae815-c9ca-4a85-89b3-470ceecda3d5\" id=\"309ae815-c9ca-4a85-89b3-470ceecda3d5-link\">85<\/a><\/sup> El trabajo de este grupo dio lugar a un ap\u00e9ndice de la directriz para la evaluaci\u00f3n de carcinogenicidad de productos farmac\u00e9uticos (ICH S1B) que brinda la oportunidad de evitar el uso de 400 animales por cada evaluaci\u00f3n regulatoria farmac\u00e9utica.<sup data-fn=\"62381a26-6545-403f-86ab-f9cfd6481fc4\" class=\"fn\"><a href=\"#62381a26-6545-403f-86ab-f9cfd6481fc4\" id=\"62381a26-6545-403f-86ab-f9cfd6481fc4-link\">86<\/a><\/sup> Una iniciativa similar, \u00a0denominada Rethinking Chronic Toxicity and Carcinogenicity Assessment for Agrochemicals Project (ReCAAP) y liderada por PETA Science Consortium International, desarroll\u00f3 un marco para respaldar una evaluaci\u00f3n basada en WoE de plaguicidas sin pruebas de carcinogenicidad a largo plazo en ratas y ratones.<sup data-fn=\"0519179d-dfec-4d2d-88ac-aa11ce79feed\" class=\"fn\"><a href=\"#0519179d-dfec-4d2d-88ac-aa11ce79feed\" id=\"0519179d-dfec-4d2d-88ac-aa11ce79feed-link\">87<\/a><\/sup> El marco ReCAAP ha sido aceptado para su publicaci\u00f3n por el Grupo de Trabajo de la OCDE para la Evaluaci\u00f3n de Peligros (WPHA), mediante el cual ocho organismos reguladores globales respaldaron el enfoque basado en WoE para satisfacer las necesidades de evaluaci\u00f3n de seguridad, sin realizar pruebas de por vida en ratas y ratones.<sup data-fn=\"8482d88e-9e26-430b-af2f-d45c8223f45d\" class=\"fn\"><a href=\"#8482d88e-9e26-430b-af2f-d45c8223f45d\" id=\"8482d88e-9e26-430b-af2f-d45c8223f45d-link\">88<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Adem\u00e1s, se est\u00e1n llevando a cabo actividades para desarrollar un marco para evaluar la carcinogenicidad de sustancias qu\u00edmicas no genot\u00f3xicas, incluidas las iniciativas del grupo de expertos sobre carcin\u00f3genos no genot\u00f3xicos (NGTxC) del Grupo de Trabajo para el Programa de Directrices de Ensayo (WNT) de la OCDE. Este marco ofrece un enfoque modular para evaluar e integrar datos <em>in vitro<\/em> e <em>in silico<\/em> en un estilo de AOP para determinar la bioactividad que podr\u00eda conducir a la carcinogenicidad.<sup data-fn=\"ab57f630-4813-4bfb-869e-b22bc24fd304\" class=\"fn\"><a href=\"#ab57f630-4813-4bfb-869e-b22bc24fd304\" id=\"ab57f630-4813-4bfb-869e-b22bc24fd304-link\">89<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">La OCDE WNT tambi\u00e9n est\u00e1 evaluando los ensayos de transformaci\u00f3n celular <em>in vitro<\/em> (CTA) por su capacidad para reproducir un proceso multietapa que modele algunos aspectos de la carcinog\u00e9nesis <em>in vivo<\/em>. El CTA tiene el potencial de detectar tanto carcin\u00f3genos genot\u00f3xicos como no genot\u00f3xicos.<sup data-fn=\"8cfec6c8-10cd-416d-b493-8bc6dda782a1\" class=\"fn\"><a href=\"#8cfec6c8-10cd-416d-b493-8bc6dda782a1\" id=\"8cfec6c8-10cd-416d-b493-8bc6dda782a1-link\">90<\/a><\/sup> En su recomendaci\u00f3n sobre el CTA basado en la l\u00ednea celular Bhas 42, EURL ECVAM se\u00f1ala que la informaci\u00f3n sobre el potencial transformador de las sustancias generada por los CTA puede ser suficiente para la toma de decisiones.<sup data-fn=\"e713f163-c0e0-4cbb-bf38-1455d83ae8c7\" class=\"fn\"><a href=\"#e713f163-c0e0-4cbb-bf38-1455d83ae8c7\" id=\"e713f163-c0e0-4cbb-bf38-1455d83ae8c7-link\">91<\/a><\/sup> Tras un estudio en el que el CTA Bhas 42 se prob\u00f3 con 98 sustancias, incluidos carcin\u00f3genos humanos conocidos, la OCDE recomend\u00f3 que este ensayo se use como parte de una estrategia de pruebas para ayudar a evaluar sustancias potencialmente cancer\u00edgenas.<sup data-fn=\"7487bf75-4dee-435d-b4ca-6d00eca6b11b\" class=\"fn\"><a href=\"#7487bf75-4dee-435d-b4ca-6d00eca6b11b\" id=\"7487bf75-4dee-435d-b4ca-6d00eca6b11b-link\">92<\/a><\/sup><sup data-fn=\"de8ee2cd-e044-4a2a-8fcb-df647214dde0\" class=\"fn\"><a href=\"#de8ee2cd-e044-4a2a-8fcb-df647214dde0\" id=\"de8ee2cd-e044-4a2a-8fcb-df647214dde0-link\">93<\/a><\/sup> Cuando se combinan con otra informaci\u00f3n, como datos de genotoxicidad, an\u00e1lisis de estructura-actividad e informaci\u00f3n toxicocin\u00e9tica, los CTA en general, y el CTA Bhas 42 en particular, pueden contribuir a la evaluaci\u00f3n del potencial carcinog\u00e9nico y ofrecer una alternativa a las pruebas <em>in vivo<\/em>.<sup data-fn=\"289072bb-56f7-4655-934c-f2a2e2d261af\" class=\"fn\"><a href=\"#289072bb-56f7-4655-934c-f2a2e2d261af\" id=\"289072bb-56f7-4655-934c-f2a2e2d261af-link\">94<\/a><\/sup><sup data-fn=\"dd640367-c523-4dff-b60c-eb0bea38228b\" class=\"fn\"><a href=\"#dd640367-c523-4dff-b60c-eb0bea38228b\" id=\"dd640367-c523-4dff-b60c-eb0bea38228b-link\">95<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Varios modelos y herramientas computacionales ayudan adem\u00e1s a evaluar el potencial de carcinogenicidad. Las alertas estructurales que se\u00f1alan posibles carcin\u00f3genos no genot\u00f3xicos se han incorporado en la herramienta OECD QSAR Toolbox.<sup data-fn=\"b8ab613b-6c44-428e-8e60-48360edcb14b\" class=\"fn\"><a href=\"#b8ab613b-6c44-428e-8e60-48360edcb14b\" id=\"b8ab613b-6c44-428e-8e60-48360edcb14b-link\">96<\/a><\/sup> Adem\u00e1s, la EPA public\u00f3 OncoLogic\u2122, un modelo inform\u00e1tico para evaluar el potencial carcinog\u00e9nico de sustancias qu\u00edmicas.<sup data-fn=\"11a2128b-fc1e-41d4-a16c-4c9618b919cd\" class=\"fn\"><a href=\"#11a2128b-fc1e-41d4-a16c-4c9618b919cd\" id=\"11a2128b-fc1e-41d4-a16c-4c9618b919cd-link\">97<\/a><\/sup> Tambi\u00e9n existen opciones comerciales, como las de Lhasa Limited, MultiCASE, UL Cheminformatics e Instem. En \u00faltima instancia, la identificaci\u00f3n de sustancias qu\u00edmicas reactivas con el ADN mediante la prueba de Ames o alertas estructurales genot\u00f3xicas puede combinarse con la identificaci\u00f3n de carcin\u00f3genos no genot\u00f3xicos mediante alertas estructurales, dejando a los CTA modelar la mayor parte de lo que queda sin explicar en un enfoque basado en WoE.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Dada la complejidad de la carcinog\u00e9nesis, los expertos reconocen que es necesario integrar nuevos enfoques (por ejemplo, <em>in silico<\/em> o <em>in vitro<\/em>) para respaldar una evaluaci\u00f3n de seguridad adecuada basada en WoE.<sup data-fn=\"05b99e61-27b1-4d3f-acc7-7bdb27ef153d\" class=\"fn\"><a href=\"#05b99e61-27b1-4d3f-acc7-7bdb27ef153d\" id=\"05b99e61-27b1-4d3f-acc7-7bdb27ef153d-link\">98<\/a><\/sup> Por fortuna, se est\u00e1n llevando a cabo iniciativas para facilitar la integraci\u00f3n de m\u00e9todos y lograr, finalmente, una evaluaci\u00f3n de carcinogenicidad sin animales, r\u00e1pida y relevante para humanos en la regulaci\u00f3n qu\u00edmica y farmac\u00e9utica.<sup data-fn=\"56022168-59e1-44aa-87ee-2deea8224c7f\" class=\"fn\"><a href=\"#56022168-59e1-44aa-87ee-2deea8224c7f\" id=\"56022168-59e1-44aa-87ee-2deea8224c7f-link\">99<\/a><\/sup><sup data-fn=\"b033c82c-d5d6-4134-9b01-4bd07b5e6055\" class=\"fn\"><a href=\"#b033c82c-d5d6-4134-9b01-4bd07b5e6055\" id=\"b033c82c-d5d6-4134-9b01-4bd07b5e6055-link\">100<\/a><\/sup><sup data-fn=\"9d023d3f-5814-467e-89b6-1c78bb6e03f9\" class=\"fn\"><a href=\"#9d023d3f-5814-467e-89b6-1c78bb6e03f9\" id=\"9d023d3f-5814-467e-89b6-1c78bb6e03f9-link\">101<\/a><\/sup><sup data-fn=\"9b597eb0-bd6f-4f04-a7a0-ab777e5bf3c1\" class=\"fn\"><a href=\"#9b597eb0-bd6f-4f04-a7a0-ab777e5bf3c1\" id=\"9b597eb0-bd6f-4f04-a7a0-ab777e5bf3c1-link\">102<\/a><\/sup><\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>Fot<strong>otoxicidad<\/strong><\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Las sustancias que absorben luz en el rango UV y visible (290 a 700 nm) y que pueden llegar a la piel o a los ojos podr\u00edan requerir pruebas para determinar su potencial fototoxicidad o la respuesta t\u00f3xica a una sustancia administrada por v\u00eda t\u00f3pica o sist\u00e9mica que ocurre tras exponerse a la luz. La fototoxicidad puede causar s\u00edntomas que van desde quemaduras de primer grado (enrojecimiento, picaz\u00f3n y dolor) hasta quemaduras de tercer grado. La fototoxicidad, tambi\u00e9n llamada fotosensibilidad, es un efecto adverso bien conocido de muchos medicamentos, incluidos los antimicrobianos, antiinflamatorios no esteroideos, diur\u00e9ticos y agentes quimioterap\u00e9uticos.<sup data-fn=\"5ef543a0-6f82-430e-926a-49be3a15b0b2\" class=\"fn\"><a href=\"#5ef543a0-6f82-430e-926a-49be3a15b0b2\" id=\"5ef543a0-6f82-430e-926a-49be3a15b0b2-link\">103<\/a><\/sup><\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-9&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-9-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-9\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-9\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-9-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Las pruebas de fototoxicidad para compuestos administrados por v\u00eda sist\u00e9mica o t\u00f3pica se han realizado en diversas especies, como cobayos, ratones y ratas. Sin embargo, no se ha establecido un dise\u00f1o de estudio <em>in vivo<\/em> validado o estandarizado.<sup data-fn=\"5f337f2c-6c15-41e4-954e-a2eba2772b2c\" class=\"fn\"><a href=\"#5f337f2c-6c15-41e4-954e-a2eba2772b2c\" id=\"5f337f2c-6c15-41e4-954e-a2eba2772b2c-link\">104<\/a><\/sup><sup data-fn=\"4b3792af-fdcd-448c-af6f-c7c558ac5a0b\" class=\"fn\"><a href=\"#4b3792af-fdcd-448c-af6f-c7c558ac5a0b\" id=\"4b3792af-fdcd-448c-af6f-c7c558ac5a0b-link\">105<\/a><\/sup> En cambio, hasta ahora se han desarrollado tres directrices de prueba de la OCDE usando m\u00e9todos <em>in chemico<\/em> e <em>in vitro<\/em> para evaluar la fototoxicidad:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Prueba de la OCDE Nro. 495: Ensayo de especies reactivas de ox\u00edgeno (ROS) para fotorreactividad.<\/strong> Este m\u00e9todo <em>in chemico<\/em> mide la capacidad de una sustancia para generar especies reactivas de ox\u00edgeno bajo exposici\u00f3n a la luz solar artificial.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 432: Ensayo <em>in vitro<\/em> 3T3 NRU de fototoxicidad.<\/strong> Esta prueba mide la viabilidad de una l\u00ednea celular de rat\u00f3n incubada con un potencial fotot\u00f3xico y expuesta a la luz.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 498: Fototoxicidad <em>in vitro<\/em>. M\u00e9todo de ensayo de fototoxicidad con epidermis humana reconstruida.<\/strong> En esta prueba, un modelo tridimensional de epidermis humana reconstruida se incuba con el potencial fotot\u00f3xico y se expone a la luz.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Esta \u00faltima prueba (Nro. 498) se basa en un principio similar al de la Nro. 432, pero usa un modelo tridimensional de piel humana reconstruida en lugar de la l\u00ednea celular de rat\u00f3n. Esto ampl\u00eda el dominio de aplicabilidad a una mayor selecci\u00f3n de sustancias, incluidas formulaciones finales, mezclas complejas o parches dermatol\u00f3gicos.<sup data-fn=\"6ecfe6da-c2c1-4763-ac63-db688070f43b\" class=\"fn\"><a href=\"#6ecfe6da-c2c1-4763-ac63-db688070f43b\" id=\"6ecfe6da-c2c1-4763-ac63-db688070f43b-link\">106<\/a><\/sup> Las sustancias con un pH extremo tambi\u00e9n pueden evaluarse con modelos tridimensionales de piel.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">De acuerdo con el Documento de Orientaci\u00f3n de la OCDE sobre Enfoques Integrados para Pruebas y Evaluaci\u00f3n (IATA) para determinar la fototoxicidad, estas directrices pueden combinarse con otras evaluaciones fisicoqu\u00edmicas y m\u00e9todos <em>in vitro<\/em> e <em>in silico<\/em>, sin animales, para estimar el potencial fotot\u00f3xico de una sustancia.<sup data-fn=\"b74a702d-c183-4611-b62e-34720066b76c\" class=\"fn\"><a href=\"#b74a702d-c183-4611-b62e-34720066b76c\" id=\"b74a702d-c183-4611-b62e-34720066b76c-link\">107<\/a><\/sup><\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><strong>Pirogenicidad<\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Las agencias reguladoras exigen pruebas para demostrar que determinados medicamentos y dispositivos m\u00e9dicos no est\u00e1n contaminados con sustancias que desencadenan una respuesta febril. Estas sustancias, denominadas pir\u00f3genos, son qu\u00edmica y estructuralmente diversas, pero suelen causar fiebre en humanos mediante un mecanismo com\u00fan: los monocitos y macr\u00f3fagos de la sangre perif\u00e9rica detectan los pir\u00f3genos y liberan citocinas proinflamatorias que inducen un aumento de la temperatura corporal. Existen dos m\u00e9todos <em>in vitro<\/em> disponibles para detectar pir\u00f3genos:<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-10&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-10-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-10\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-10\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-10-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<ul class=\"wp-block-list\">\n<li><strong>Ensayo de activaci\u00f3n de monocitos (MAT)<\/strong>, definido en el cap\u00edtulo general 2.6.30 de la Farmacopea Europea (<em>Ph. Eur.<\/em>) y permitido en el cap\u00edtulo general 151 de la Farmacopea de Estados Unidos (USP).<\/li>\n\n\n\n<li><strong>Ensayo con Factor C recombinante (rFC)<\/strong>, definido en el cap\u00edtulo general 2.6.32 de la <em>Ph. Eur.<\/em> y, a partir de mayo de 2025, en el cap\u00edtulo general 86 de la USP.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Aunque el mecanismo de la respuesta febril humana se conoce bien, a\u00fan es frecuente que las instancias reguladoras globales requieran dos pruebas en animales para evaluar la contaminaci\u00f3n por pir\u00f3genos. En la prueba de pir\u00f3genos en conejos (RPT), se inyecta a los animales una sustancia de prueba y luego se les inmoviliza durante tres horas, tiempo en el que se monitorean los cambios en su temperatura corporal de forma rectal. Solo en la UE y Noruega, m\u00e1s de 125 mil conejos fueron usados entre 2018 y 2022 en la RPT.<sup data-fn=\"1e540447-5bb3-47d9-843c-ceb92056d4a7\" class=\"fn\"><a href=\"#1e540447-5bb3-47d9-843c-ceb92056d4a7\" id=\"1e540447-5bb3-47d9-843c-ceb92056d4a7-link\">108<\/a><\/sup> Algunos pa\u00edses parecen haber dejado de usar la RPT. Sin embargo, Francia y Espa\u00f1a usaron m\u00e1s de 6 mil animales cada uno en la RPT en 2022, a pesar de que nunca se ha validado formalmente la relevancia de esta prueba para los humanos y sus resultados pueden variar seg\u00fan el nivel de estr\u00e9s del animal. Tambi\u00e9n existen diferencias en la sensibilidad a los pir\u00f3genos entre especies y la prueba es incompatible con ciertas clases de medicamentos.<sup data-fn=\"d6e264f9-d7dc-4428-8153-e0086f61b11d\" class=\"fn\"><a href=\"#d6e264f9-d7dc-4428-8153-e0086f61b11d\" id=\"d6e264f9-d7dc-4428-8153-e0086f61b11d-link\">109<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">La prueba de lisado de amebocitos de Limulus (LAL) requiere el uso de hemolinfa de cangrejos herradura capturados y solo detecta endotoxinas bacterianas, no otros pir\u00f3genos. Despu\u00e9s del proceso de sangrado, hasta el 30% de los cangrejos muere y aquellos que se recuperan tienen menos probabilidades de sobrevivir en la naturaleza.<sup data-fn=\"d363d428-ae11-41cf-afa1-bbbe9d5f1658\" class=\"fn\"><a href=\"#d363d428-ae11-41cf-afa1-bbbe9d5f1658\" id=\"d363d428-ae11-41cf-afa1-bbbe9d5f1658-link\">110<\/a><\/sup> Una versi\u00f3n sint\u00e9tica del LAL, en la que la hemolinfa se reemplaza por un reactivo recombinante (el ensayo rFC), est\u00e1 disponible para detectar endotoxinas bacterianas. El ensayo rFC es una prueba confiable y respetuosa con los animales, con un desempe\u00f1o igual o superior al de la prueba LAL.<sup data-fn=\"d6a5cb34-9fee-48cc-ac2a-405c02cabe78\" class=\"fn\"><a href=\"#d6a5cb34-9fee-48cc-ac2a-405c02cabe78\" id=\"d6a5cb34-9fee-48cc-ac2a-405c02cabe78-link\">111<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Desde 2010, el ensayo <em>in vitro<\/em> de activaci\u00f3n de monocitos (MAT), capaz de detectar tanto pir\u00f3genos endot\u00f3xicos como no endot\u00f3xicos, ha sido validado e incluido en la <em>Ph. Eur<\/em>.<sup data-fn=\"3fa3e5c4-dab7-494b-81b5-302518a86acf\" class=\"fn\"><a href=\"#3fa3e5c4-dab7-494b-81b5-302518a86acf\" id=\"3fa3e5c4-dab7-494b-81b5-302518a86acf-link\">112<\/a><\/sup> En el MAT, los medicamentos y dispositivos m\u00e9dicos se incuban con sangre humana entera o monocitos humanos aislados. Despu\u00e9s de este per\u00edodo de exposici\u00f3n, se miden las citocinas proinflamatorias liberadas por los monocitos.<sup data-fn=\"e42d0328-e4df-4398-aaac-862a53b4e408\" class=\"fn\"><a href=\"#e42d0328-e4df-4398-aaac-862a53b4e408\" id=\"e42d0328-e4df-4398-aaac-862a53b4e408-link\">113<\/a><\/sup> El MAT evita los problemas mencionados anteriormente con las pruebas RPT y LAL y, como se ha documentado en estudios de caso, este ensayo ha detectado contaminaci\u00f3n por pir\u00f3genos en productos que hab\u00edan pasado las pruebas RPT y LAL pero causaron fiebre en pacientes humanos.<sup data-fn=\"f8dfbd6f-2895-4036-b73d-7ee6d65791f2\" class=\"fn\"><a href=\"#f8dfbd6f-2895-4036-b73d-7ee6d65791f2\" id=\"f8dfbd6f-2895-4036-b73d-7ee6d65791f2-link\">114<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Los reguladores en India, la UE, el Reino Unido y EE. UU., as\u00ed como las farmacopeas usadas en estas regiones, permiten el uso del MAT y del rFC tras la validaci\u00f3n para un producto espec\u00edfico. No obstante, las pruebas en animales siguen realiz\u00e1ndose a pesar de que sus limitaciones se han documentado a profundidad.<sup data-fn=\"6cb5d0da-e998-467d-a439-d32d97975175\" class=\"fn\"><a href=\"#6cb5d0da-e998-467d-a439-d32d97975175\" id=\"6cb5d0da-e998-467d-a439-d32d97975175-link\">115<\/a><\/sup> Para eliminar el uso de animales en las pruebas de pir\u00f3genos, las entidades regulatorias y las organizaciones de normalizaci\u00f3n deben esforzarse m\u00e1s para integrar y armonizar una preferencia por las pruebas sin animales en los requisitos internacionales y para alentar a los fabricantes de medicamentos y dispositivos a usar y presentar datos de estas pruebas en sus solicitudes de aprobaci\u00f3n. En septiembre de 2018, los participantes en un taller organizado por PETA Science Consortium International y NICEATM discutieron enfoques sin animales para las pruebas de pir\u00f3genos en dispositivos m\u00e9dicos y solicitaron m\u00e1s oportunidades de capacitaci\u00f3n y educaci\u00f3n para aumentar el uso del MAT con fines regulatorios.<sup data-fn=\"75d705e0-2b68-420e-9870-f2ee7d17c8b9\" class=\"fn\"><a href=\"#75d705e0-2b68-420e-9870-f2ee7d17c8b9\" id=\"75d705e0-2b68-420e-9870-f2ee7d17c8b9-link\">116<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Tras una encuesta a usuarios de pruebas de pir\u00f3genos, la Direcci\u00f3n Europea de Calidad de Medicamentos y Atenci\u00f3n Sanitaria (EDQM) revis\u00f3 el cap\u00edtulo general de la <em>Ph. Eur.<\/em> sobre el MAT para hacerlo m\u00e1s accesible y enfatizar que se considera un reemplazo de las pruebas de pir\u00f3genos en animales.<sup data-fn=\"fa2eccac-dd70-4eec-b5a1-087265885601\" class=\"fn\"><a href=\"#fa2eccac-dd70-4eec-b5a1-087265885601\" id=\"fa2eccac-dd70-4eec-b5a1-087265885601-link\">117<\/a><\/sup><sup data-fn=\"b5e3b31f-8a3d-4734-818c-616ceb5e9660\" class=\"fn\"><a href=\"#b5e3b31f-8a3d-4734-818c-616ceb5e9660\" id=\"b5e3b31f-8a3d-4734-818c-616ceb5e9660-link\">118<\/a><\/sup> La Agencia Europea de Medicamentos tambi\u00e9n ha aprobado el MAT,<sup data-fn=\"2a00865a-fb9c-448f-946e-737d24c98650\" class=\"fn\"><a href=\"#2a00865a-fb9c-448f-946e-737d24c98650\" id=\"2a00865a-fb9c-448f-946e-737d24c98650-link\">119<\/a><\/sup> y la Comisi\u00f3n de la <em>Ph. Eur.<\/em> elimin\u00f3 la RPT de la <em>Ph. Eur.<\/em> en 2025.<sup data-fn=\"15766bf1-1021-46ea-b34d-5e2a29b32fc5\" class=\"fn\"><a href=\"#15766bf1-1021-46ea-b34d-5e2a29b32fc5\" id=\"15766bf1-1021-46ea-b34d-5e2a29b32fc5-link\">120<\/a><\/sup> La Organizaci\u00f3n Internacional de Normalizaci\u00f3n (ISO) est\u00e1 revisando su gu\u00eda para permitir el uso del MAT para \u00a0evaluar la contaminaci\u00f3n por pir\u00f3genos en dispositivos m\u00e9dicos, pero el proceso de revisi\u00f3n ha avanzado lentamente.<sup data-fn=\"7d41e727-533e-4512-a7fa-4755a7282e3a\" class=\"fn\"><a href=\"#7d41e727-533e-4512-a7fa-4755a7282e3a\" id=\"7d41e727-533e-4512-a7fa-4755a7282e3a-link\">121<\/a><\/sup> En la octava edici\u00f3n de la Farmacopea India, la Comisi\u00f3n de la Farmacopea India revis\u00f3 el cap\u00edtulo general sobre pruebas de pir\u00f3genos, introdujo la monograf\u00eda sobre el MAT y reemplaz\u00f3 la RPT por LAL.<sup data-fn=\"3d1c5224-7412-437d-89c3-bdcc7db2909f\" class=\"fn\"><a href=\"#3d1c5224-7412-437d-89c3-bdcc7db2909f\" id=\"3d1c5224-7412-437d-89c3-bdcc7db2909f-link\">122<\/a><\/sup> Sin embargo, debido a la falta de claridad y la ambig\u00fcedad regulatoria sobre la aplicabilidad del MAT como prueba independiente de pir\u00f3genos, la RPT y el LAL contin\u00faan us\u00e1ndose.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><strong><strong>Toxicidad reproductiva y del desarrollo<\/strong><\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Los estudios de toxicidad reproductiva y del desarrollo miden el efecto de una sustancia qu\u00edmica en los \u00f3rganos reproductivos y en la descendencia en desarrollo durante el embarazo.<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-11&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-11-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-11\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-11\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-11-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Los estudios de toxicidad del desarrollo para la evaluaci\u00f3n de la seguridad de productos qu\u00edmicos y farmac\u00e9uticos para los humanos se realizan principalmente en ratas. Sin embargo, muchos marcos regulatorios, incluidas las normativas sobre productos biocidas y fitosanitarios y, en algunas circunstancias, REACH en la UE, exigen que los solicitantes presenten resultados de pruebas en una segunda especie, generalmente conejos, bajo el supuesto de que existen diferencias entre especies en la sensibilidad a los efectos sobre el desarrollo. Estas pruebas usan un gran n\u00famero de animales. Por ejemplo, un estudio estim\u00f3 que el n\u00famero total de animales usados para los par\u00e1metros reproductivos y de desarrollo en los expedientes de registro existentes de la base de datos p\u00fablica de la ECHA (a diciembre de 2022) es aproximadamente 2,7 millones.<sup data-fn=\"cd48ba56-fee7-408f-84b9-24aa1c880c2c\" class=\"fn\"><a href=\"#cd48ba56-fee7-408f-84b9-24aa1c880c2c\" id=\"cd48ba56-fee7-408f-84b9-24aa1c880c2c-link\">123<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Ninguno de los m\u00e9todos <em>in vivo<\/em> usados para evaluar la toxicidad reproductiva y del desarrollo ha sido validado formalmente por su relevancia para los humanos,<sup data-fn=\"be95d9c7-1ee1-4688-af1c-853297ddb417\" class=\"fn\"><a href=\"#be95d9c7-1ee1-4688-af1c-853297ddb417\" id=\"be95d9c7-1ee1-4688-af1c-853297ddb417-link\">124<\/a><\/sup> y las evaluaciones retrospectivas han encontrado limitaciones significativas y subjetividad en la interpretaci\u00f3n de los datos.<sup data-fn=\"d065e727-d358-4e4e-8c15-36762dad6433\" class=\"fn\"><a href=\"#d065e727-d358-4e4e-8c15-36762dad6433\" id=\"d065e727-d358-4e4e-8c15-36762dad6433-link\">125<\/a><\/sup><sup data-fn=\"43403ae8-0d4b-4293-9ef4-040d248e7174\" class=\"fn\"><a href=\"#43403ae8-0d4b-4293-9ef4-040d248e7174\" id=\"43403ae8-0d4b-4293-9ef4-040d248e7174-link\">126<\/a><\/sup> Por lo tanto, se requiere una inversi\u00f3n considerable para desarrollar m\u00e9todos sin animales que sean relevantes para los humanos. Recientemente, se incluyeron 42 AOP del AOP-wiki relevantes para la toxicidad reproductiva en mam\u00edferos en una red de AOP para la toxicidad reproductiva mediada por estr\u00f3genos, andr\u00f3genos y esteroidog\u00e9nesis. Estas AOPs abarcan efectos sobre niveles o actividad hormonal, c\u00e1ncer, sistemas reproductivos masculino y femenino, y efectos generales sobre la fertilidad y la reproducci\u00f3n.<sup data-fn=\"1afd0a05-2761-405c-9651-7b13c03d80f2\" class=\"fn\"><a href=\"#1afd0a05-2761-405c-9651-7b13c03d80f2\" id=\"1afd0a05-2761-405c-9651-7b13c03d80f2-link\">127<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Debido al amplio conocimiento sobre los eventos clave de la toxicidad reproductiva y del desarrollo, se han desarrollado muchos ensayos y bater\u00edas de pruebas prometedoras. El proyecto EU ReProTect, que ten\u00eda como objetivo desarrollar m\u00e9todos innovadores para evaluar la toxicidad reproductiva, demostr\u00f3 que una bater\u00eda de varias pruebas <em>in vitro<\/em> e <em>in silico<\/em>, incluida la prueba con c\u00e9lulas madre embrionarias, pod\u00eda proporcionar informaci\u00f3n valiosa sobre efectos adversos durante el desarrollo embrionario.<sup data-fn=\"697af840-0c3d-4620-83a3-e32733db9ce4\" class=\"fn\"><a href=\"#697af840-0c3d-4620-83a3-e32733db9ce4\" id=\"697af840-0c3d-4620-83a3-e32733db9ce4-link\">128<\/a><\/sup> Un ensayo novedoso basado en biomarcadores de c\u00e9lulas madre humanas, ReproTracker\u00ae, identifica el potencial teratog\u00e9nico de las sustancias qu\u00edmicas.<sup data-fn=\"38cdd535-2774-4a5d-9fca-c85d451dd8bd\" class=\"fn\"><a href=\"#38cdd535-2774-4a5d-9fca-c85d451dd8bd\" id=\"38cdd535-2774-4a5d-9fca-c85d451dd8bd-link\">129<\/a><\/sup> Adem\u00e1s, se desarroll\u00f3 una bater\u00eda de pruebas que incluye el ensayo de activaci\u00f3n transcripcional CALUX (para actividad esteroidog\u00e9nica), el ensayo ReProGlo (para el patr\u00f3n del eje corporal y la especificaci\u00f3n del destino celular), la prueba con c\u00e9lulas madre embrionarias (para diferenciaci\u00f3n en cardiomiocitos) y el ensayo de embriotoxicidad en pez cebra.<sup data-fn=\"ef68bd1c-b7f9-4f7b-8994-8f213fa4eb9b\" class=\"fn\"><a href=\"#ef68bd1c-b7f9-4f7b-8994-8f213fa4eb9b\" id=\"ef68bd1c-b7f9-4f7b-8994-8f213fa4eb9b-link\">130<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Asimismo, el proyecto EU-ToxRisk integra avances en biolog\u00eda celular, tecnolog\u00eda \u201c\u00f3mica\u201d, biolog\u00eda de sistemas y modelado computacional para definir las cadenas complejas de eventos que vinculan la exposici\u00f3n qu\u00edmica con los resultados t\u00f3xicos. El proyecto se centra en la toxicidad sist\u00e9mica por dosis repetidas y en la toxicidad reproductiva y del desarrollo. El Centro Nacional de Toxicolog\u00eda Computacional de la EPA tambi\u00e9n explora el potencial de las sustancias qu\u00edmicas para alterar el desarrollo prenatal mediante el uso de su modelo virtual de embri\u00f3n, v-Embryo\u2122, que integra enfoques de modelado <em>in vitro<\/em> e <em>in silico<\/em>.<sup data-fn=\"8466c141-253f-4300-a08f-a2f28a15b0b4\" class=\"fn\"><a href=\"#8466c141-253f-4300-a08f-a2f28a15b0b4\" id=\"8466c141-253f-4300-a08f-a2f28a15b0b4-link\">131<\/a><\/sup> La OCDE, el JRC, la Autoridad Europea de Seguridad Alimentaria (EFSA) y la EPA han desarrollado recomendaciones que demuestran que la integraci\u00f3n de una bater\u00eda de ensayos <em>in vitro<\/em> puede usarse para determinar el potencial de neurotoxicidad de las sustancias qu\u00edmicas en el desarrollo, y las agencias asociadas est\u00e1n trabajando en estudios de caso que se aplican a diferentes clases de sustancias qu\u00edmicas.<sup data-fn=\"e69b53d9-1649-48e7-b116-fede07638a98\" class=\"fn\"><a href=\"#e69b53d9-1649-48e7-b116-fede07638a98\" id=\"e69b53d9-1649-48e7-b116-fede07638a98-link\">132<\/a><\/sup><sup data-fn=\"d31341d3-f2b9-4c59-a6d0-014647ae2045\" class=\"fn\"><a href=\"#d31341d3-f2b9-4c59-a6d0-014647ae2045\" id=\"d31341d3-f2b9-4c59-a6d0-014647ae2045-link\">133<\/a><\/sup><sup data-fn=\"9cb3e8bf-1321-4357-a1af-00c4432c7c08\" class=\"fn\"><a href=\"#9cb3e8bf-1321-4357-a1af-00c4432c7c08\" id=\"9cb3e8bf-1321-4357-a1af-00c4432c7c08-link\">134<\/a><\/sup> Un estudio compar\u00f3 los puntos de partida basados en bioactividad <em>in vitro<\/em> (POD<sub>Bioactivity<\/sub>) con los puntos de partida de estudios orales de dosis repetidas, desarrollo y reproducci\u00f3n (POD<sub>Traditional<\/sub>) usados en la evaluaci\u00f3n de riesgos. Para 43 de las 46 sustancias qu\u00edmicas examinadas, el POD<sub>Bioactivity<\/sub> fue m\u00e1s conservador que el valor m\u00e1s bajo del POD<sub>Traditional<\/sub>, lo que indica que la bioactividad <em>in vitro<\/em> puede usarse como una estimaci\u00f3n sustituta del l\u00edmite inferior de los niveles de efectos adversos <em>in vivo<\/em>,ya que ser\u00eda al menos tan protectora como usar POD<sub>Traditional<\/sub>.<sup data-fn=\"80b25eeb-7c58-4e44-a85d-a082a990db65\" class=\"fn\"><a href=\"#80b25eeb-7c58-4e44-a85d-a082a990db65\" id=\"80b25eeb-7c58-4e44-a85d-a082a990db65-link\">135<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Si bien el campo avanza gradualmente hacia una gama de estrategias integradoras para cubrir la mayor\u00eda de los mecanismos posibles, se requiere mucha m\u00e1s investigaci\u00f3n.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><strong><strong>Irritaci\u00f3n\/corrosi\u00f3n cut\u00e1nea<\/strong><\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Varias agencias reguladoras requieren o recomiendan realizar pruebas de irritaci\u00f3n y corrosi\u00f3n cut\u00e1nea para sustancias qu\u00edmicas. En la prueba en animales, se aplica la sustancia a evaluar sobre la piel rasurada de un conejo y se observa durante 14 d\u00edas para evaluar el grado de da\u00f1o cut\u00e1neo. Las pruebas pueden causar da\u00f1o permanente en la piel, \u00falceras, sangrado, costras y cicatrices.<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-12&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-12-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-12\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-12\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-12-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Los estudios de irritaci\u00f3n cut\u00e1nea en animales se han usado durante a\u00f1os, a pesar de que se ha demostrado que, en general, son predictores deficientes de las reacciones cut\u00e1neas humanas y altamente variables.<sup data-fn=\"77e6ebec-7b28-40a1-8c6a-0fa28292c663\" class=\"fn\"><a href=\"#77e6ebec-7b28-40a1-8c6a-0fa28292c663\" id=\"77e6ebec-7b28-40a1-8c6a-0fa28292c663-link\">136<\/a><\/sup> Por ejemplo, un estudio que compar\u00f3 datos de pruebas en conejos y pruebas de parche cut\u00e1neo de cuatro horas en humanos para 65 sustancias encontr\u00f3 que el 45% de las clasificaciones del potencial irritante qu\u00edmico basadas en pruebas en animales eran incorrectas.<sup data-fn=\"0fc82c9a-5c48-4ab3-9475-d6f6ef1a75b9\" class=\"fn\"><a href=\"#0fc82c9a-5c48-4ab3-9475-d6f6ef1a75b9\" id=\"0fc82c9a-5c48-4ab3-9475-d6f6ef1a75b9-link\">137<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Con base en los criterios descritos en la gu\u00eda Nro. 237 de la OCDE, existen oportunidades para evitar las pruebas en animales.<sup data-fn=\"23a2471c-3dee-4167-b2aa-ef755d2be8c0\" class=\"fn\"><a href=\"#23a2471c-3dee-4167-b2aa-ef755d2be8c0\" id=\"23a2471c-3dee-4167-b2aa-ef755d2be8c0-link\">138<\/a><\/sup> Adem\u00e1s, la OCDE ha desarrollado un IATA para irritaci\u00f3n cut\u00e1nea con m\u00e9todos <em>in vitro<\/em> que evitan o minimizan el uso de animales.<sup data-fn=\"bdf71489-f36a-44fc-8bc5-e6934066924d\" class=\"fn\"><a href=\"#bdf71489-f36a-44fc-8bc5-e6934066924d\" id=\"bdf71489-f36a-44fc-8bc5-e6934066924d-link\">139<\/a><\/sup><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Prueba de la OCDE Nro. 439: Ensayo <em>in vitro<\/em> de irritaci\u00f3n cut\u00e1nea con epidermis humana reconstruida (RHE). <\/strong>Esta prueba puede usarse para la identificaci\u00f3n del peligro asociado con sustancias qu\u00edmicas irritantes (sustancias y mezclas) de categor\u00eda 2 o no clasificadas, de acuerdo con el GHS. Puede usarse como prueba independiente o en una estrategia escalonada.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 431: Ensayo de corrosi\u00f3n cut\u00e1nea <em>in vitro <\/em>con RHE.<\/strong> Esta prueba puede usarse para identificar sustancias y mezclas qu\u00edmicas corrosivas, as\u00ed como para distinguir entre corrosivos cut\u00e1neos graves y menos graves.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 435: Ensayo <em>in vitro<\/em> de barrera de membrana para corrosi\u00f3n cut\u00e1nea.<\/strong> Esta prueba permite clasificar las sustancias qu\u00edmicas corrosivas en una de las tres subcategor\u00edas de corrosividad del GHS..<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Recientemente, la <strong>gu\u00eda de prueba Nro. 439 de la OCDE<\/strong> fue validada para su uso en la evaluaci\u00f3n de la capacidad de los extractos de dispositivos m\u00e9dicos para causar irritaci\u00f3n cut\u00e1nea, y la gu\u00eda ISO 10993 se ha actualizado para incluir esta prueba.<sup data-fn=\"b1d3fae7-a1fd-4452-b9f9-c6971b408581\" class=\"fn\"><a href=\"#b1d3fae7-a1fd-4452-b9f9-c6971b408581\" id=\"b1d3fae7-a1fd-4452-b9f9-c6971b408581-link\">140<\/a><\/sup><\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><strong><strong>Sensibilizaci\u00f3n cut\u00e1nea<\/strong><\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">La evaluaci\u00f3n de la sensibilizaci\u00f3n cut\u00e1nea mide la probabilidad de que una sustancia cause una reacci\u00f3n al\u00e9rgica si se aplica sobre la piel. La prueba en animales implica inyectarles a cobayos la sustancia a evaluar o aplicarla sobre su piel rasurada, en lo que se conoce como prueba de maximizaci\u00f3n en cobayos, o aplicarla en las orejas de ratones en el ensayo del ganglio linf\u00e1tico local.<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-13&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-13-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-13\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-13\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-13-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">El requisito regulatorio para evaluar la sensibilizaci\u00f3n cut\u00e1nea puede cumplirse mediante un enfoque definido, tal como se describe en la <strong>Prueba de la OCDE Nro. 497<\/strong> (enfoques definidos para la sensibilizaci\u00f3n cut\u00e1nea), usando una combinaci\u00f3n de ensayos <em>in chemico<\/em> e <em>in vitro<\/em> que abordan diferentes eventos clave en la AOP.<sup data-fn=\"1223eb3a-89ce-48f4-909d-5782532036fc\" class=\"fn\"><a href=\"#1223eb3a-89ce-48f4-909d-5782532036fc\" id=\"1223eb3a-89ce-48f4-909d-5782532036fc-link\">141<\/a><\/sup> El enfoque definido \u201c2 de 3\u201d proporciona informaci\u00f3n suficiente para la identificaci\u00f3n del peligro, y las pruebas integradas (ITSv1 e ITSv2) recopilan informaci\u00f3n de dos de los ensayos <em>in vitro <\/em>listados a continuaci\u00f3n y predicciones <em>in silico<\/em> del peligro y la potencia.<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Prueba de la OCDE Nro. 442C: Ensayos de sensibilizaci\u00f3n cut\u00e1nea <em>in chemico<\/em> que abordan el evento clave de la AOP sobre la uni\u00f3n covalente a prote\u00ednas.<\/strong> Esta prueba aborda el evento molecular inicial de la AOP de sensibilizaci\u00f3n cut\u00e1nea.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 442D: Ensayos de sensibilizaci\u00f3n cut\u00e1nea <em>in vitro<\/em> que abordan el evento clave de la AOP sobre la activaci\u00f3n de queratinocitos.<\/strong> Esta prueba aborda el segundo evento clave de la AOP de sensibilizaci\u00f3n cut\u00e1nea.<\/li>\n\n\n\n<li><strong>Prueba de la OCDE Nro. 442E: Ensayos de sensibilizaci\u00f3n cut\u00e1nea <em>in vitro<\/em> que abordan el evento clave sobre la activaci\u00f3n de c\u00e9lulas dendr\u00edticas.<\/strong> Esta prueba aborda el tercer evento clave del AOP de sensibilizaci\u00f3n cut\u00e1nea.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Cuando se comparan con datos provenientes de humanos, los enfoques sin animales para predecir la sensibilizaci\u00f3n cut\u00e1nea son tan buenos o mejores que el ensayo del ganglio linf\u00e1tico local.<sup data-fn=\"3970d2b8-da08-4d3f-97d3-09417f71bec7\" class=\"fn\"><a href=\"#3970d2b8-da08-4d3f-97d3-09417f71bec7\" id=\"3970d2b8-da08-4d3f-97d3-09417f71bec7-link\">142<\/a><\/sup><\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h2 class=\"wp-block-heading\"><strong><strong>Toxicidad sist\u00e9mica<\/strong><\/strong><\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><strong><strong>Toxicidad sist\u00e9mica aguda<\/strong><\/strong><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Para determinar el peligro de la exposici\u00f3n a un producto o sustancia qu\u00edmica, se administra la sustancia a animales por v\u00eda oral, d\u00e9rmica o inhalatoria. La toxicidad aguda se refiere a los efectos adversos observados despu\u00e9s de una exposici\u00f3n \u00fanica a un nivel elevado de una sustancia durante un per\u00edodo corto (hasta 24 horas). En estas pruebas se determina la dosis en la que morir\u00eda la mitad de los animales, denominada dosis letal 50 (DL50) o concentraci\u00f3n letal 50 (CL50) para pruebas por inhalaci\u00f3n. La prueba DL50 y sus adaptaciones nunca han sido validadas cient\u00edficamente y su precisi\u00f3n para predecir los efectos qu\u00edmicos en humanos sigue siendo cuestionable. Un an\u00e1lisis de la variabilidad de la prueba animal de toxicidad oral aguda mostr\u00f3 que la exactitud para obtener la misma clasificaci\u00f3n de la EPA o del GHS, respectivamente, es del 78% o 74% cuando la misma sustancia qu\u00edmica se prueba m\u00e1s de una vez.<sup data-fn=\"0908d2f3-3ba7-4bd1-9f0a-20a70151e465\" class=\"fn\"><a href=\"#0908d2f3-3ba7-4bd1-9f0a-20a70151e465\" id=\"0908d2f3-3ba7-4bd1-9f0a-20a70151e465-link\">143<\/a><\/sup> Otro an\u00e1lisis de datos existentes de DL50 oral aguda demostr\u00f3 que los estudios replicados resultan en la misma categorizaci\u00f3n de peligro en promedio el 60% de las veces.<sup data-fn=\"e8d708bb-2b63-4c41-beb9-bf84d271cd20\" class=\"fn\"><a href=\"#e8d708bb-2b63-4c41-beb9-bf84d271cd20\" id=\"e8d708bb-2b63-4c41-beb9-bf84d271cd20-link\">144<\/a><\/sup> Este an\u00e1lisis tambi\u00e9n demostr\u00f3 que la variabilidad biol\u00f3gica o del protocolo subyacente probablemente explica la variaci\u00f3n en los resultados.<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-14&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-14-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-14\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-14\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-14-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Cuando se proporciona justificaci\u00f3n cient\u00edfica, las autoridades regulatorias pueden permitir la evaluaci\u00f3n de toxicidad aguda sin pruebas en animales. La OCDE ha publicado directrices para la exenci\u00f3n o la integraci\u00f3n de pruebas de toxicidad aguda<sup data-fn=\"c87dad8e-2106-46af-95ea-d83ba2d3d435\" class=\"fn\"><a href=\"#c87dad8e-2106-46af-95ea-d83ba2d3d435\" id=\"c87dad8e-2106-46af-95ea-d83ba2d3d435-link\">145<\/a><\/sup> y la EPA ha publicado gu\u00edas similares para plaguicidas y pesticidas.<sup data-fn=\"adefae3e-5f6d-4de8-856f-7983be5fb736\" class=\"fn\"><a href=\"#adefae3e-5f6d-4de8-856f-7983be5fb736\" id=\"adefae3e-5f6d-4de8-856f-7983be5fb736-link\">146<\/a><\/sup> Esto incluye el uso de datos existentes para <em>read-across <\/em>y la consideraci\u00f3n de las propiedades fisicoqu\u00edmicas de la sustancia de prueba.<sup data-fn=\"efc09532-bd59-487b-9a8b-a297b2da382c\" class=\"fn\"><a href=\"#efc09532-bd59-487b-9a8b-a297b2da382c\" id=\"efc09532-bd59-487b-9a8b-a297b2da382c-link\">147<\/a><\/sup><sup data-fn=\"6bb1d781-dfdc-4e25-952c-9451b50c98b4\" class=\"fn\"><a href=\"#6bb1d781-dfdc-4e25-952c-9451b50c98b4\" id=\"6bb1d781-dfdc-4e25-952c-9451b50c98b4-link\">148<\/a><\/sup><\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h3 class=\"wp-block-heading\"><strong><strong>Toxicidad sist\u00e9mica por dosis repetidas<\/strong><\/strong><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">En los estudios de toxicidad por dosis repetidas, los animales son expuestos reiteradamente a sustancias durante un mes (subaguda), tres meses (subcr\u00f3nica) o varios a\u00f1os (cr\u00f3nica) para medir los efectos de m\u00faltiples exposiciones a sustancias qu\u00edmicas, las cuales suelen administrarse a los animales mediante una sonda (<em>gavage<\/em>), a menos que se prevea que los humanos estar\u00e1n m\u00e1s expuestos por otra v\u00eda. Como ocurre con otros par\u00e1metros, la evidencia muestra que los estudios regulatorios que usan animales para evaluar la toxicidad por dosis repetidas no cumplen adecuadamente su prop\u00f3sito y, por ello, existe una clara necesidad de desarrollar nuevos enfoques. Dos estudios publicados en 2020 evaluaron las fuentes de variabilidad en los valores usados para derivar niveles seguros de exposici\u00f3n a partir de pruebas de dosis repetidas en roedores y encontraron que aproximadamente un tercio de la variaci\u00f3n total no pod\u00eda explicarse a partir de diferencias en los protocolos, por ejemplo, la v\u00eda de administraci\u00f3n.<sup data-fn=\"88af6ddd-6699-4ff6-b1b8-55da2d47a5d9\" class=\"fn\"><a href=\"#88af6ddd-6699-4ff6-b1b8-55da2d47a5d9\" id=\"88af6ddd-6699-4ff6-b1b8-55da2d47a5d9-link\">149<\/a><\/sup><sup data-fn=\"4fda4490-a1f6-421d-aa0e-a00b598d3fb2\" class=\"fn\"><a href=\"#4fda4490-a1f6-421d-aa0e-a00b598d3fb2\" id=\"4fda4490-a1f6-421d-aa0e-a00b598d3fb2-link\">150<\/a><\/sup><\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-15&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-15-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-15\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-15\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-15-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">La evaluaci\u00f3n de la toxicidad por dosis repetidas es un requisito est\u00e1ndar en las evaluaciones de seguridad para los humanos. Aunque los enfoques <em>read-across<\/em> son aceptados con fines regulatorios, otros m\u00e9todos sin animales a\u00fan no han logrado una aceptaci\u00f3n completa. Para abordar esta brecha en el uso de m\u00e9todos sin animales, diversos proyectos en el \u00e1mbito acad\u00e9mico, industrial y regulatorio han propuesto conjuntos variados de ensayos <em>in vitro<\/em> e <em>in silico<\/em> basados en tecnolog\u00edas \u201c\u00f3micas\u201d y de alto contenido y rendimiento. Estas iniciativas se centran en desarrollar m\u00e9todos de prueba sin animales para derivar puntos de partida <em>in vitro<\/em>, predecir concentraciones plasm\u00e1ticas m\u00e1ximas o calcular tasas de exposici\u00f3n a la bioactividad.<sup data-fn=\"35569b37-3601-4f8d-87e2-08162da1ee32\" class=\"fn\"><a href=\"#35569b37-3601-4f8d-87e2-08162da1ee32\" id=\"35569b37-3601-4f8d-87e2-08162da1ee32-link\">151<\/a><\/sup><sup data-fn=\"75a33a8d-2297-4d90-91ee-c3be59137faf\" class=\"fn\"><a href=\"#75a33a8d-2297-4d90-91ee-c3be59137faf\" id=\"75a33a8d-2297-4d90-91ee-c3be59137faf-link\">152<\/a><\/sup><sup data-fn=\"f0d55f36-67fc-4d24-bab2-9de41a9d32e4\" class=\"fn\"><a href=\"#f0d55f36-67fc-4d24-bab2-9de41a9d32e4\" id=\"f0d55f36-67fc-4d24-bab2-9de41a9d32e4-link\">153<\/a><\/sup><sup data-fn=\"107a4e3f-8dbb-427c-969a-5d90423ec171\" class=\"fn\"><a href=\"#107a4e3f-8dbb-427c-969a-5d90423ec171\" id=\"107a4e3f-8dbb-427c-969a-5d90423ec171-link\">154<\/a><\/sup> Un estudio de caso de la OCDE sobre el uso de un IATA para la toxicidad sist\u00e9mica demuestra la aplicaci\u00f3n de estas metodolog\u00edas avanzadas.<sup data-fn=\"49bc0ac8-6687-400c-a761-1f8b9be68f44\" class=\"fn\"><a href=\"#49bc0ac8-6687-400c-a761-1f8b9be68f44\" id=\"49bc0ac8-6687-400c-a761-1f8b9be68f44-link\">155<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Mientras contin\u00faan desarroll\u00e1ndose e implement\u00e1ndose sistemas de prueba <em>in vitro <\/em>en el \u00e1mbito regulatorio, el n\u00famero de animales usados en pruebas de toxicidad por dosis repetidas bajo diversos marcos normativos puede reducirse inmediatamente mediante la extrapolaci\u00f3n de puntos de partida de estudios subcr\u00f3nicos a estudios cr\u00f3nicos.<sup data-fn=\"2e5468bf-8bae-41b2-a43c-5151ed12eef9\" class=\"fn\"><a href=\"#2e5468bf-8bae-41b2-a43c-5151ed12eef9\" id=\"2e5468bf-8bae-41b2-a43c-5151ed12eef9-link\">156<\/a><\/sup> Una revisi\u00f3n de los puntos de partida (NOAELs o LOAELs) determinados a partir de estudios <em>in vivo<\/em> de aditivos alimentarios mostr\u00f3 que los valores cr\u00f3nicos pueden extrapolarse de manera confiable a partir de estudios subcr\u00f3nicos, respaldando an\u00e1lisis previos de otros tipos de sustancias, incluidos productos qu\u00edmicos industriales y plaguicidas. La evaluaci\u00f3n del riesgo y la derivaci\u00f3n de valores de referencia basados en la salud pueden fortalecerse a\u00fan m\u00e1s con la aplicaci\u00f3n precautoria de un factor adicional de incertidumbre de 2 para tener en cuenta cualquier valor at\u00edpico, lo cual recomiendan la EFSA y varios estudios recientes.<sup data-fn=\"8c7ed4a7-ca50-48b3-b709-7833beff167f\" class=\"fn\"><a href=\"#8c7ed4a7-ca50-48b3-b709-7833beff167f\" id=\"8c7ed4a7-ca50-48b3-b709-7833beff167f-link\">157<\/a><\/sup><\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>V\u00eda oral<\/strong><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">NICEATM y el Comit\u00e9 Interinstitucional de Coordinaci\u00f3n para la Validaci\u00f3n de M\u00e9todos Alternativos (ICCVAM) llevaron a cabo un proyecto para desarrollar modelos predictivos de toxicidad sist\u00e9mica oral aguda.<sup data-fn=\"1f1d32a9-f74e-46aa-81f8-3946f81ff05f\" class=\"fn\"><a href=\"#1f1d32a9-f74e-46aa-81f8-3946f81ff05f\" id=\"1f1d32a9-f74e-46aa-81f8-3946f81ff05f-link\">158<\/a><\/sup> El resultado fue la herramienta <em>Collaborative Acute Toxicity Modelling Suite<\/em> (CATMoS), que predice la toxicidad oral aguda y satisface diversos requisitos normativos.<sup data-fn=\"2e49ae72-bb82-4565-8627-bac98e5d3154\" class=\"fn\"><a href=\"#2e49ae72-bb82-4565-8627-bac98e5d3154\" id=\"2e49ae72-bb82-4565-8627-bac98e5d3154-link\">159<\/a><\/sup> Esta herramienta gener\u00f3 139 modelos predictivos con datos de aproximadamente 12.000 sustancias qu\u00edmicas y, tras ponderar el desempe\u00f1o de cada uno de estos, se construy\u00f3 un modelo combinado. CATMoS se implementa a trav\u00e9s de la aplicaci\u00f3n <em>Open Structure-Activity\/Property Relationship<\/em> (OPERA), una herramienta QSAR de c\u00f3digo abierto y acceso gratuito.<sup data-fn=\"8ba153a2-fbab-40f7-9667-5748dd69ce53\" class=\"fn\"><a href=\"#8ba153a2-fbab-40f7-9667-5748dd69ce53\" id=\"8ba153a2-fbab-40f7-9667-5748dd69ce53-link\">160<\/a><\/sup> Este modelo se optimiza y eval\u00faa con frecuencia,<sup data-fn=\"994a0d06-719e-42c6-9f7a-2e0a69f5f5e8\" class=\"fn\"><a href=\"#994a0d06-719e-42c6-9f7a-2e0a69f5f5e8\" id=\"994a0d06-719e-42c6-9f7a-2e0a69f5f5e8-link\">161<\/a><\/sup> y las actualizaciones est\u00e1n disponibles en los sitios web de NICEATM <em>Integrated Chemical Environment<\/em> (ICE) y la EPA.<sup data-fn=\"12d07031-5a22-4600-a3c8-4f5ee6a50bb0\" class=\"fn\"><a href=\"#12d07031-5a22-4600-a3c8-4f5ee6a50bb0\" id=\"12d07031-5a22-4600-a3c8-4f5ee6a50bb0-link\">162<\/a><\/sup> PETA Science Consortium International, PCRM y la EPA desarrollaron seminarios web sobre la herramienta CATMoS y la base de datos ICE (<a href=\"https:\/\/www.thepsci.eu\/training-videos-webinars\/\">ThePSCI.eu\/training-videos-webinars<\/a>).<\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-16&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-16-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-16\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-16\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-16-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">EURL ECVAM recomienda el ensayo <em>in vitro<\/em> de citotoxicidad 3T3 con absorci\u00f3n de rojo neutro (NRU), que puede emplearse en un enfoque WoE para respaldar la identificaci\u00f3n de sustancias no clasificadas.<sup data-fn=\"9f3ee706-1d5c-49a4-9054-084e1917e72c\" class=\"fn\"><a href=\"#9f3ee706-1d5c-49a4-9054-084e1917e72c\" id=\"9f3ee706-1d5c-49a4-9054-084e1917e72c-link\">163<\/a><\/sup> Adem\u00e1s, EURL ECVAM investig\u00f3 c\u00f3mo aumentar la confianza en el ensayo 3T3 NRU mediante el uso de QSAR y considerando informaci\u00f3n sobre el \u00f3rgano diana y la falta de metabolismo en las c\u00e9lulas 3T3.<sup data-fn=\"a116db8b-6b57-4ad6-a82f-2df3592cb69b\" class=\"fn\"><a href=\"#a116db8b-6b57-4ad6-a82f-2df3592cb69b\" id=\"a116db8b-6b57-4ad6-a82f-2df3592cb69b-link\">164<\/a><\/sup><sup data-fn=\"f3c28a0a-03e3-42af-92ca-cd5f8aaa8649\" class=\"fn\"><a href=\"#f3c28a0a-03e3-42af-92ca-cd5f8aaa8649\" id=\"f3c28a0a-03e3-42af-92ca-cd5f8aaa8649-link\">165<\/a><\/sup><sup data-fn=\"f591331a-e41a-4ef9-b13e-694599069850\" class=\"fn\"><a href=\"#f591331a-e41a-4ef9-b13e-694599069850\" id=\"f591331a-e41a-4ef9-b13e-694599069850-link\">166<\/a><\/sup><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">En su Gu\u00eda sobre los requisitos de informaci\u00f3n y la evaluaci\u00f3n de la seguridad qu\u00edmica, ECHA indica que se puede evitar un estudio <em>in vivo<\/em> de toxicidad oral aguda si el solicitante dispone de datos relevantes dentro de un enfoque WoE.<sup data-fn=\"b35ab0ee-d8e1-44e7-901b-afc9addbf4d7\" class=\"fn\"><a href=\"#b35ab0ee-d8e1-44e7-901b-afc9addbf4d7\" id=\"b35ab0ee-d8e1-44e7-901b-afc9addbf4d7-link\">167<\/a><\/sup> En los casos en que la adaptaci\u00f3n mediante WoE lleve a asumir una toxicidad oral aguda baja o nula (>2000 mg\/kg de peso corporal\/d\u00eda), el solicitante puede evitar las pruebas en animales de acuerdo con los art\u00edculos 13(1) y 25(1) de REACH.<sup data-fn=\"5e2feb46-25ae-401d-a886-06dd7fa3ab4b\" class=\"fn\"><a href=\"#5e2feb46-25ae-401d-a886-06dd7fa3ab4b\" id=\"5e2feb46-25ae-401d-a886-06dd7fa3ab4b-link\">168<\/a><\/sup> En <a href=\"https:\/\/www.thepsci.eu\/training-videos-webinars\/\">ThePSCI.eu\/training-videos-webinars<\/a> encontrar\u00e1s m\u00e1s informaci\u00f3n sobre c\u00f3mo reducir el n\u00famero de animales usados para evaluar la toxicidad oral aguda en el marco de REACH.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>V\u00eda d\u00e9rmica<\/strong><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">La EPA y el NICEATM analizaron las contribuciones relativas de los datos de las pruebas de toxicidad oral y d\u00e9rmica aguda a la clasificaci\u00f3n y etiquetado de los riesgos asociados con los plaguicidas. Dado que se determin\u00f3 que los datos d\u00e9rmicos aportaban poco o ning\u00fan valor adicional en la toma de decisiones regulatorias, la EPA public\u00f3 una gu\u00eda que permite a los solicitantes presentar una justificaci\u00f3n cient\u00edfica s\u00f3lida para demostrar que los resultados de la prueba oral aguda son protectores frente a posibles efectos d\u00e9rmicos agudos.<sup data-fn=\"b8562a2e-3cda-43cf-80d6-22bcffccfd28\" class=\"fn\"><a href=\"#b8562a2e-3cda-43cf-80d6-22bcffccfd28\" id=\"b8562a2e-3cda-43cf-80d6-22bcffccfd28-link\">169<\/a><\/sup><sup data-fn=\"705e6074-0f3d-4fcf-80ec-30f4db0a1697\" class=\"fn\"><a href=\"#705e6074-0f3d-4fcf-80ec-30f4db0a1697\" id=\"705e6074-0f3d-4fcf-80ec-30f4db0a1697-link\">170<\/a><\/sup> Adem\u00e1s, no se requieren estudios d\u00e9rmicos para sustancias que no est\u00e1n clasificadas para la v\u00eda oral y que no se absorben por v\u00eda d\u00e9rmica.<sup data-fn=\"2ac0b94e-3308-4de1-bade-5d6f50c1d69b\" class=\"fn\"><a href=\"#2ac0b94e-3308-4de1-bade-5d6f50c1d69b\" id=\"2ac0b94e-3308-4de1-bade-5d6f50c1d69b-link\">171<\/a><\/sup> Asimismo, de acuerdo con el Anexo VIII de REACH, las sustancias no clasificadas para la v\u00eda oral no requieren datos d\u00e9rmicos.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>V\u00eda inhalatoria<\/strong><\/h3>\n\n\n\n<p class=\"wp-block-paragraph\">Las pruebas por v\u00eda inhalatoria pueden evitarse con base en par\u00e1metros fisicoqu\u00edmicos (p. ej., baja volatilidad) o si la exposici\u00f3n por inhalaci\u00f3n es improbable (p. ej., en casos en los que la sustancia no se vuelva aerosol ni respirable bajo las condiciones de uso). Cuando se requiere realizar pruebas, se pueden usar m\u00e9todos sin animales para cumplir con los requisitos de informaci\u00f3n. Por ejemplo, la EPA acept\u00f3 el uso de una prueba de biosolubilidad <em>in chemico<\/em>, que mostr\u00f3 que un pol\u00edmero, inicialmente clasificado como una sustancia de baja solubilidad y\u00a0 toxicidad, era soluble en un fluido pulmonar epitelial simulado y, por lo tanto, no representaba riesgo por sobrecarga pulmonar.<sup data-fn=\"28d8af58-d984-497a-bc7d-81f07196f73d\" class=\"fn\"><a href=\"#28d8af58-d984-497a-bc7d-81f07196f73d\" id=\"28d8af58-d984-497a-bc7d-81f07196f73d-link\">172<\/a><\/sup> Asimismo, en lugar de un estudio de inhalaci\u00f3n de 90 d\u00edas en ratas, la EPA acept\u00f3 datos de modelado <em>in silico<\/em> de din\u00e1mica de fluidos y pruebas <em>in vitro<\/em> con tejidos pulmonares humanos tridimensionales reconstruidos para cumplir con los requisitos de renovaci\u00f3n de registro de un pesticida.<sup data-fn=\"a0401102-bb43-49c8-a534-f53a79c63c3e\" class=\"fn\"><a href=\"#a0401102-bb43-49c8-a534-f53a79c63c3e\" id=\"a0401102-bb43-49c8-a534-f53a79c63c3e-link\">173<\/a><\/sup><sup data-fn=\"251b5ff0-c407-449c-a2e3-0a1aea6b4dc4\" class=\"fn\"><a href=\"#251b5ff0-c407-449c-a2e3-0a1aea6b4dc4\" id=\"251b5ff0-c407-449c-a2e3-0a1aea6b4dc4-link\">174<\/a><\/sup> Adem\u00e1s, se est\u00e1n llevando a cabo otras investigaciones prometedoras para desarrollar m\u00e9todos sin animales para la toxicidad por inhalaci\u00f3n.<sup data-fn=\"4a5eafe8-ef1e-4f31-850f-603ce90b375c\" class=\"fn\"><a href=\"#4a5eafe8-ef1e-4f31-850f-603ce90b375c\" id=\"4a5eafe8-ef1e-4f31-850f-603ce90b375c-link\">175<\/a><\/sup><\/p>\n\n\n\n<div data-wp-context=\"{ &quot;autoclose&quot;: false, &quot;accordionItems&quot;: [] }\" data-wp-interactive=\"core\/accordion\" role=\"group\" class=\"wp-block-accordion is-layout-flow wp-block-accordion-is-layout-flow\">\n<div data-wp-class--is-open=\"state.isOpen\" data-wp-context=\"{ &quot;id&quot;: &quot;accordion-item-17&quot;, &quot;openByDefault&quot;: false }\" data-wp-init=\"callbacks.initAccordionItems\" data-wp-on-window--hashchange=\"callbacks.hashChange\" class=\"wp-block-accordion-item is-layout-flow wp-block-accordion-item-is-layout-flow\">\n<h3 class=\"wp-block-accordion-heading\"><button aria-expanded=\"false\" aria-controls=\"accordion-item-17-panel\" data-wp-bind--aria-expanded=\"state.isOpen\" data-wp-on--click=\"actions.toggle\" data-wp-on--keydown=\"actions.handleKeyDown\" id=\"accordion-item-17\" type=\"button\" class=\"wp-block-accordion-heading__toggle\"><span class=\"wp-block-accordion-heading__toggle-title\">Lee m\u00e1s<\/span><span class=\"wp-block-accordion-heading__toggle-icon\" aria-hidden=\"true\">+<\/span><\/button><\/h3>\n\n\n\n<div inert aria-labelledby=\"accordion-item-17\" data-wp-bind--inert=\"!state.isOpen\" id=\"accordion-item-17-panel\" role=\"region\" class=\"wp-block-accordion-panel is-layout-flow wp-block-accordion-panel-is-layout-flow\">\n<p class=\"wp-block-paragraph\">PETA Science Consortium International ha organizado numerosos seminarios web (<a href=\"http:\/\/www.thepsci.eu\/inhalation-webinars\">ThePSCI.eu\/inhalation-webinars<\/a>) y talleres sobre varios enfoques que eventualmente podr\u00edan reemplazar las pruebas en animales para este par\u00e1metro,<sup data-fn=\"ff101319-5973-4676-baf8-5cf84646c4ef\" class=\"fn\"><a href=\"#ff101319-5973-4676-baf8-5cf84646c4ef\" id=\"ff101319-5973-4676-baf8-5cf84646c4ef-link\">176<\/a><\/sup><sup data-fn=\"0457343f-cac9-4c1a-82af-3e31794b3fcd\" class=\"fn\"><a href=\"#0457343f-cac9-4c1a-82af-3e31794b3fcd\" id=\"0457343f-cac9-4c1a-82af-3e31794b3fcd-link\">177<\/a><\/sup> ha financiado el desarrollo de m\u00e9todos y ha implementado mecanismos de apoyo para proporcionar equipos y tejidos respiratorios <em>in vitro <\/em>para realizar estudios de toxicidad por inhalaci\u00f3n.<sup data-fn=\"a2f04eef-7b33-4ca5-bcac-1f51e018e95a\" class=\"fn\"><a href=\"#a2f04eef-7b33-4ca5-bcac-1f51e018e95a\" id=\"a2f04eef-7b33-4ca5-bcac-1f51e018e95a-link\">178<\/a><\/sup> En <a href=\"https:\/\/www.thepsci.eu\/our-work\/inhalation\/\">ThePSCI.eu\/our-work\/inhalation<\/a> encontrar\u00e1s m\u00e1s informaci\u00f3n sobre las pruebas de toxicidad por inhalaci\u00f3n.<\/p>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-columns footnotes is-layout-flex wp-container-core-columns-is-layout-8f761849 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<h5 class=\"wp-block-heading\">ReferencIAS<\/h5>\n\n\n<ol class=\"wp-block-footnotes\"><li id=\"52872122-9fc8-4669-a3d0-2964de330a81\">OECD. Integrated approaches to testing and assessment (IATA). 2021. Accessed October 15, 2021.\u00a0<a href=\"https:\/\/www.oecd.org\/en\/topics\/sub-issues\/assessment-of-chemicals\/integrated-approaches-to-testing-and-assessment.html\" target=\"_blank\" rel=\"noreferrer noopener\">https:\/\/www.oecd.org\/en\/topics\/sub-issues\/assessment-of-chemicals\/integrated-approaches-to-testing-and-assessment.html<\/a>) <a href=\"#52872122-9fc8-4669-a3d0-2964de330a81-link\" aria-label=\"Jump to footnote reference 1\">\u21a9\ufe0e<\/a><\/li><li id=\"72f4fd39-c1a6-4e63-8f42-cad5b9968f69\">OECD. Guidance document on the reporting of defined approaches to be used within integrated approaches to testing and assessment. OECD Series on Testing and Assessment, No. 255. April 13, 2017. Accessed November 7, 2024. <a href=\"https:\/\/doi.org\/10.1787\/9789264274822-en\">https:\/\/doi.org\/10.1787\/9789264274822-en<\/a> <a href=\"#72f4fd39-c1a6-4e63-8f42-cad5b9968f69-link\" aria-label=\"Jump to footnote reference 2\">\u21a9\ufe0e<\/a><\/li><li id=\"9fd22cad-bee7-4a43-b95c-d4a05c6193c6\">OECD. Guideline No. 497: Defined approaches on skin sensitisation. OECD Guidelines for the Testing of Chemicals, Section 4. July 4, 2023. Accessed March 25, 2025. https:\/\/doi.org\/10.1787\/b92879a4-en <a href=\"#9fd22cad-bee7-4a43-b95c-d4a05c6193c6-link\" aria-label=\"Jump to footnote reference 3\">\u21a9\ufe0e<\/a><\/li><li id=\"9cf8989f-fa20-4295-85a7-73ff03bf74d5\">OECD. Guidance document for the use of adverse outcome pathways in developing integrated approaches to testing and assessment (IATA). OECD Series on Testing and Assessment, No. 260. March 10, 2017. Accessed November 7, 2024. <a href=\"https:\/\/doi.org\/10.1787\/44bb06c1-en\">https:\/\/doi.org\/10.1787\/44bb06c1-en<\/a> <a href=\"#9cf8989f-fa20-4295-85a7-73ff03bf74d5-link\" aria-label=\"Jump to footnote reference 4\">\u21a9\ufe0e<\/a><\/li><li id=\"54775efd-1607-4d58-ab28-f4c7cd33935e\">Ball N. Developing the scientific basis for exposure based adaptations (EBA)\u2013technical report no 137. European Centre for Ecotoxicology and Toxicology of Chemicals. October 2, 2020. 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Accessed December 10, 2024. <a href=\"https:\/\/www.federalregister.gov\/d\/2021-20780\">https:\/\/www.federalregister.gov\/d\/2021-20780<\/a> <a href=\"#e530a5b7-1b5d-4310-8c94-9b80a7f9be44-link\" aria-label=\"Jump to footnote reference 10\">\u21a9\ufe0e<\/a><\/li><li id=\"8082f187-f858-4872-ab7a-483f156094d4\">ECHA. Clarity on interface between REACH and the cosmetics regulation. October 27, 2014. Accessed August 9, 2024. <a href=\"https:\/\/echa.europa.eu\/view-article\/-\/journal_content\/title\/clarity-on-interface-between-reach-and-the-cosmetics-regulation\">https:\/\/echa.europa.eu\/view-article\/-\/journal_content\/title\/clarity-on-interface-between-reach-and-the-cosmetics-regulation<\/a> <a href=\"#8082f187-f858-4872-ab7a-483f156094d4-link\" aria-label=\"Jump to footnote reference 11\">\u21a9\ufe0e<\/a><\/li><li id=\"7bb9aaed-8103-4c73-ae2a-fb64bca40077\">Dent M, Amaral RT, Da Silva PA. et al. Principles underpinning the use of new methodologies in the risk assessment of cosmetic ingredients. <em>Comput Toxicol.<\/em> 2018;7:20-26. <a href=\"#7bb9aaed-8103-4c73-ae2a-fb64bca40077-link\" aria-label=\"Jump to footnote reference 12\">\u21a9\ufe0e<\/a><\/li><li id=\"f0b9f027-033d-4419-80e1-6f74c96dff28\">Fentem JH. The 19<sup>th<\/sup> FRAME Annual Lecture, November 2022: Safer chemicals and sustainable innovation will be achieved by regulatory use of modern safety science, not by more animal testing. <em>Altern Lab Anim. <\/em>2023;51(2):90-101 <a href=\"#f0b9f027-033d-4419-80e1-6f74c96dff28-link\" aria-label=\"Jump to footnote reference 13\">\u21a9\ufe0e<\/a><\/li><li id=\"bf5d49c3-17f6-40d5-9884-e822ee60d81e\">Berggren E, White A, Ouedraogo G, et al. 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Accessed December 3, 2024. <a href=\"https:\/\/questions-statements.parliament.uk\/written-statements\/detail\/2023-05-17\/hcws779\">https:\/\/questions-statements.parliament.uk\/written-statements\/detail\/2023-05-17\/hcws779<\/a> <a href=\"#76bc44ee-ac33-42a7-8eec-afa4fd2daafc-link\" aria-label=\"Jump to footnote reference 21\">\u21a9\ufe0e<\/a><\/li><li id=\"c4e015b2-4ff4-4443-8a90-bb9e6c246b98\">Tugendhat T. Animal experiments: cosmetics. Question 2844. U.K. Parliament. November 21, 2023. Accessed December 3, 2024. <a href=\"https:\/\/questions-statements.parliament.uk\/written-questions\/detail\/2023-11-21\/2844\">https:\/\/questions-statements.parliament.uk\/written-questions\/detail\/2023-11-21\/2844<\/a> <a href=\"#c4e015b2-4ff4-4443-8a90-bb9e6c246b98-link\" aria-label=\"Jump to footnote reference 22\">\u21a9\ufe0e<\/a><\/li><li id=\"7e6e76fc-51d8-4488-a946-3642cf910e2c\">European Commission. 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Use of EpiAlveolar lung model to predict fibrotic potential of multiwalled carbon nanotubes. <em>ACS Nano<\/em>. 2020;14(4):3941-3956 <a href=\"#a2f04eef-7b33-4ca5-bcac-1f51e018e95a-link\" aria-label=\"Jump to footnote reference 178\">\u21a9\ufe0e<\/a><\/li><\/ol><\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>A continuaci\u00f3n, se detallan las oportunidades para eliminar o reducir significativamente el uso de animales en la evaluaci\u00f3n de la toxicidad de sustancias en el contexto de los requisitos regulatorios en esta materia. Tambi\u00e9n se describen las \u00e1reas en las que se requiere un mayor apoyo para desarrollar m\u00e9todos innovadores que sean relevantes para la&#8230;<\/p>\n","protected":false},"author":4,"featured_media":0,"parent":0,"menu_order":2,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":"[{\"id\":\"52872122-9fc8-4669-a3d0-2964de330a81\",\"content\":\"OECD. 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April 13, 2017. Accessed January 17, 2025. https:\/\/doi.org\/10.1787\/9789264274754-en\"},{\"id\":\"28d8af58-d984-497a-bc7d-81f07196f73d\",\"content\":\"EPA. Revocation of significant new use rule for a certain chemical substance (P-16-581), 85 FR 52274. August 25, 2020 (to be codified at 40 CFR 721)\"},{\"id\":\"a0401102-bb43-49c8-a534-f53a79c63c3e\",\"content\":\"EPA. Chlorothalonil: Revised human health draft risk assessment for registration review. May 21, 2021. Accessed March 26, 2025. <a href=\\\"https:\/\/www.regulations.gov\/document\/EPA-HQ-OPP-2011-0840-0080\\\">https:\/\/www.regulations.gov\/document\/EPA-HQ-OPP-2011-0840-0080<\/a>\"},{\"id\":\"251b5ff0-c407-449c-a2e3-0a1aea6b4dc4\",\"content\":\"OECD. Case study on the use of an integrated approach for testing and assessment (IATA) for new approach methodology (NAM) for refining inhalation risk assessment from point of contact toxicity of the pesticide, chlorothalonil. OECD Series on Testing and Assessment, No. 367. 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Use of EpiAlveolar lung model to predict fibrotic potential of multiwalled carbon nanotubes. <em>ACS Nano<\/em>. 2020;14(4):3941-3956\"}]"},"secton":[18],"class_list":["post-822","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Evaluaci\u00f3n de la toxicidad - Modernicemos la Investigaci\u00f3n YA<\/title>\n<meta name=\"description\" content=\"PETA Scientists&#039; comprehensive report on the use of animals in experimentation, testing, and education, and common-sense strategy for revitalizing the U.S. scientific enterprise to protect human health and the environment.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/science.peta.org\/es\/evaluacion-de-la-toxicidad\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Evaluaci\u00f3n de la toxicidad - 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