Toxicity of Contaminants

Objectives / Objetivos

To study the mechanisms underlying the toxic effects of environmental pollutants, particularly on fish, using in vitro and in vivo approaches, taking into account bioaccumulation processes, and concentrating on emerging contaminants as endocrine disrupters, manufactured nanomaterials or mycotoxins. To develop, by combining chemistry and biology approaches, tools for the detection toxic effects on wild animals, environmental samples, feed and food. To identify safer manufactured nanomaterials that could be applied in agricultural systems with different purposes. To contribute to the development of tools for the risk assessment of nanomaterials and chemicals.

Keywords: cytochrome P4501A, endocrine disruption, toxicokinetics, nanoparticle, toxicity mechanisms.

Estudiar los mecanismos subyacentes al efecto tóxico de contaminantes ambientales, particularmente en peces, mediante aproximaciones in vitro e in vivo y centrándonos en contaminantes emergentes como disruptores endocrinos, nanomateriales o micotoxinas. Desarrollar, combinando aproximaciones químicas y biológicas, herramientas para detectar efectos tóxicos en organismos salvajes, en muestras ambientales, en piensos o en alimentos. Identificar nanomateriales más seguros para su aplicación en sistemas agrarios con diferentes objetivos. Contribuir al desarrollo de herramientas de evaluación del riesgo de nanomateriales y sustancias químicas.

Palabras clave: citocromo P4501A, disrupción endocrina, toxicocinética, nanopartícula, mecanismos de toxicidad.

R&D&i projects / Proyectos de investigación

FP7 Grant Agreement 604305 (2013-2017). SUN, Sustainable Nanotechnologies.

FP7 Grant Agreement 604387 (2013-2017). GUIDEnano, Assessment and mitigation of nano-enabled product risks on human and environmental health: Development of new strategies and creation of a digital guidance tool for nanotech industries.

H2020 Grant Agreement 646221 (2015-2018). NanoREG2. Development and implementation of Grouping and Safe-by-Design approaches within regulatory frameworks.

LIFE Grant Agreement LIFE15 ENV/ES/000416 (2016-2019). COMBASE Computational tool for the assessment and substitution of Biocidal Active Substances of Ecotoxicological concern.

National Project. RTA2012-00053-00-00 (2013-2016). Perturbación endocrina y efectos tóxicos asociados a la presencia de hormonas, antibióticos, micotoxinas y otras sustancias en residuos ganaderos y acuícolas

National Project. EG13-074 (2013-2017). Encomienda de gestión entre la Dirección General de Calidad y Evaluación Ambiental y Medio Natural y el Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) en relación con la Evaluación de los Peligros y Riesgos para el Medio Ambiente de las Sustancias y Productos Químicos de acuerdo con la Normativa Nacional y Comunitaria.

R&D&i activities / Actividades de I+D+i

We have demonstrated, by means of microarrays, that substances with thyroidal activity alter the fish immune system. Such an observation has important implications in relation to the observed decline of wild populations. We observed that manufactured nanomaterials ingested by fish are absorbed and distributed in the fish organs provoking alterations in the oxidative metabolism. We also observed in vitro that co-exposure to two nanomaterials can lead to a synergistic toxic effect, due to the fact that one of the nanomaterials favour the entrance of the other one into cells. We have proposed in collaboration with other EU laboratories modifications in the OECD test guidelines for the detection and assessment of the toxicity of chemicals, so that these test guidelines could be applied to nanomaterials

Hemos demostrado, mediante la aplicación de microarrays, que sustancias con actividad tiroidea provocan alteraciones en el sistema inmune de peces lo que tiene implicaciones para el mantenimiento de poblaciones salvajes. Hemos visto que los nanomateriales ingeridos por peces se absorben y distribuyen por los órganos del pez y que provocan alteraciones en el metabolismo oxidativo. También hemos observado in vitro que la co-exposición a dos nanomateriales diferentes puede dar lugar a un efecto tóxico sinérgico al favorecer uno de los nanomateriales la absorción celular del otro. Hemos propuesto con otros laboratorios europeos modificaciones en las guías técnicas de la OCDE utilizadas para la detección y evaluación de toxicidad de productos químicos, de modo que puedan ser aplicadas a nanomateriales.

Scientific papers / Artículos científicos

Campos B, Rivetti C, Rosenkranz P, Navas JM, Barata C. 2013. Effects of nanoparticles of TiO2 on food depletion and life-history responses of Daphnia magna. Aquatic Toxicology 130-131: 174-183

Connolly M, Pérez Y, Mann E, Herradón B, Fernández-Cruz ML, Navas JM. 2013. Peptide-biphenyl hybrid-capped AuNPs: stability and biocompatibility under cell culture conditions. Nanoscale Research Letters 8: 315

De la Casa-Resino I, Hernández-Moreno D, Navas JM, Soler F, Pérez-López M. 2013. Non-destructive multibiomarker approach in European quail (Coturnix coturnix coturnix) exposed to the herbicide atrazine. Archives of Environmental Contamination and Toxicology. 65: 567-574.

Fernández-Cruz ML, Lammel T, Connolly M, Conde E, Barrado A, Sylvain D, Pérez Y, Fernández M, Furger C, Navas JM. 2013. Comparative cytotoxicity induced by bulk and nanoparticulated ZnO in the fish and human hepatoma cell lines PLHC-1 and Hep G2. Nanotoxicology 7: 935 – 952

Lammel T, Boisseaux P, Fernández-Cruz ML, Navas JM. 2013. Internalization and cytotoxicity of graphene oxide and carboxyl graphene nanoplatelets in the human hepatocellular carcinoma cell line HepG2. Particle and Fiber Toxicology. 10:27 “HIGHLY ACCESSED ARTICLE, IN THIS JOURNAL”

Malhão F, Urbatzka R, Navas JM, Cruzeiro C, Monteiro RAF, Rocha E. 2013. Cytological, immunocytochemical, ultrastructural and growth characterization of the rainbow trout liver cell line RTL-W1. Tissue and Cell. 45: 159-174

Quesada-García A, Valdehita A, Torrent F, Villarroel M, Hernando D, Navas JM. 2013. Use of fish farms to assess river contamination: combining biomarker responses, active biomonitoring, and chemical analysis. Aquatic Toxicology. 140 – 141: 439-448

Scholz S, Sela E, Blaha L, Braunbeck T, Galay-Burgos M, García-Franco M, Guinea J, Klüver N, Schirmer K, Tanneberger K, Tobor-Kapłon M, Witters H, Belanger S, Benfenati E, Creton S, Cronin MTD, Eggen RIL, Embry M, Ekman D, Gourmelon A, Halder M, Hardy B, Hartung T, Hubesch B, Jungmann D, Lampi MA, Lee L, Léonard M, Küster E, Lillicrap A, Luckenbach T, Murk AJ, Navas JM, Peijnenburg W, Repetto G, Salinas E, Schüürmann G, Spielmann H, Tollefsen KE, Walter-Rohde S, Whale G, Wheeler JR, Winter MJ. 2013. A European perspective on alternatives to animal testing for environmental hazard identification and risk assessment. Regulatory Toxicology and Pharmacology. 67: 506 - 530

De la Casa-Resino I, Navas JM, Fernández-Cruz ML. 2014. Chlorotriazines do not activate the aryl hydrocarbon receptor, the estrogen receptor and thyroid receptor in in vitro assays. ATLA. 42: 25 - 30.

Faria M, Navas JM, Soares AMVM, Barata C. 2014. Oxidative stress effects of titanium dioxide nanoparticles in zebrafish embryos. Science of the Total Environment. 470-471: 379-389

Lammel T, Navas JM. 2014. Graphene nanoplatelets spontaneously translocate into the cytosol and physically interact withcellular organelles in the fish cell line PLHC-1. Aquatic Toxicology. 150: 55-65

Oliveira E, Casado M, Faria M, Soares A, Navas JM, Barata C, Piña B. 2014. Transcriptomic response of zebrafish embryos to polyamidoamine (PAMAM) dendrimers Nanotoxicology. 8: 92-99.

Quesada-García A, Valdehita A, Kropf C, Casanova-Nakayama A, Segner H, Navas JM. 2014. Thyroid signalling in imune organs and cells of the teleost fish rainbow trout (Oncorhynchus mykiss). Fish & Shellfish Immunology. 38: 166 – 174.

Song L, Connolly M, Fernández-Cruz ML, Vijver MG, Fernández M, Conde E, de Snoo GR, Peijnenburg WJGM, Navas JM. 2014. Species specific toxicity of copper nanoparticles among mammalian and piscine cell lines. Nanotoxicology. 8: 383-393.

Tetko IV, Schramm K-W, Knepper T, Peijnenburg WJGM, Hendriks AJ, Navas JM, Nicholls IA, Öberg T, Todeschini R, Schlosser E, Brandmaier S. 2014. Experimental and theoretical studies in the EU FP7 Mrie Curie initial training network project, Environmental ChemOinformatics (ECO). ATLA 42: 7-11

Valdehita A, Quesada-García A, Delgado MM, Martín JV, García-González MC, Fernández-Cruz ML, Navas JM. 2014. In vitro assessment of thyroidal and estrogenic activities in poultry and broiler manure. Science of the Total Environment. 472: 630-641

Connolly M, Fernández-Cruz ML, Navas JM. 2015. Recovery of redox homeostasis altered by CuNPs in H4IIE liver cells does not reduce the cytotoxic effects of these NPs: An investigation using arylhydrocarbon receptor (AhR) dependent antioxidant activity. Chemico Biological Interactions. 228: 57 – 68.

Connolly M, Fernández-Cruz ML, Quesada-García A, García-Olias LA, Segner H, Navas JM.2015. Comparative cytotoxicity study of silver nanoparticles (AgNPs) in a variety of rainbow trout cell lines (RTL-W1, RTH-149, RTG-2) and primary hepatocytes. International Journal of Environmental Research and Public Health 12: 5386-5405

Lammel T, Boisseaux P, Navas JM. 2015. Potentiating effect of graphene nanomaterials on aromatic environmental pollutant-induced cytochrome P450 1A expression in the topminnow fish hepatoma cell line PLHC-1. Environmental Toxicology 30: 1192 - 1204

Lingxiangyu L, Fernández-Cruz ML, Connolly M, Conde E, Fernández M, Schuster M, Navas JM. 2015. The potentiation effect makes the difference: Non-toxic concentrations of ZnO nanoparticles enhance Cu nanoparticle toxicity in vitro.Science of the Total Environment. 505: 253-260.

Lingxiangyu L, Fernández-Cruz ML, Connolly M, Schuster M, Navas JM.2015. Dissolution and aggregation of Cu nanoparticles in culture media: Effects of incubation temperature and particle size. Journal of Nanoparticle Research. 17:38

Mary VS, Valdehita A, Navas JM, Rubinstein HR, Fernández-Cruz ML. 2015. Effects of aflatoxin B1, fumonisin B1 and their mixture on the aryl hydrocarbon receptor and the cytochrome P450 1A induction. Food and Chemical Toxicology. 75: 104-111.

Quesada-García A, Valdehita A, del Olmo I, Gómez MJ, Navas JM. 2015. Detection of effects caused by very low levels of contaminants in riverine sediments through a combination of chemical analysis, in vitro bioassays, and farmed fish as sentinels. Archives of Environmental Contamination and Toxicology. 68: 663-677

Connolly M, Fernández M, Conde E, Torrent F, Navas JM, Fernández-Cruz ML. 2016. Tissue distribution of zinc and subtle oxidative stress effects after dietary administration of ZnO nanoparticles to rainbow trout. Science of the Total Environment. 551-552: 334-343.

Quesada-García A, Encinas P, Valdehita P, Baumann L, Segner H, Coll J, Navas JM. 2016. Thyroid active agents T3 and PTU differentially affect immune gene transcripts in the head kidney of rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology. 174: 159-168.

Hernández-Moreno D, Lingxiangyu Li, Connolly M, Conde E, Fernández M, Schuster M, Navas JM, Fernández-Cruz ML. 2016. Mechanisms underlying the enhancement of toxicity caused by the co-incubation of ZnO and Cu nanoparticles in a fish hepatoma cell line. Environmental Toxicology and Chemistry. 35: 2562-2570

Fernández-Cruz ML, Martín-Cabrejas I, Pérez-del Palacio J, Gaya P, Díaz-Navarro C, Navas JM, Medina M, Arqués JL. 2016. In vitro toxicity of reuterin, a potential food biopreservative. Food and Chemical Toxicology. 96: 155-199.

Bermejo-Nogales A, Fernández M, Fernández-Cruz ML, Navas JM.2016. Toxicity of silver nanoparticles in a fish cell line (PLHC-1) is associated to interaction with cell membranes and oxidative stress. Comparative Biochemistry and Physiology C. 190: 54 - 65

Hund-Rinke K, Baun A, Cupi D, Fernandes T, Handy R, Navas JM, Peijnenburg W, Schlich K, Shaw B, Scott-Fordsmand J. 2016. Regulatory ecotoxicity testing of nanomaterials – Proposed modifications of OECD Test Guidelines based on laboratory experience with silver and titanium dioxide nanoparticles. Nanotoxicology 10: 1442 – 1447.

Valdehita A, Fernández-Cruz ML, González-Gullón MI, Becerra-Neira E, Delgado MM, García-González MC, Navas JM. 2017. Androgens and androgenic activity in broiler manure assessed by means of chemical analysis and in vitro bioassays. Environmental Toxicology and Chemistry. DOI: 10.1002/etc.3495

Bermejo-Nogales A, Connolly M, Rosenkranz P, Fernández-Cruz ML, Navas JM. 2017 Negligible cytotoxicity induced by different titanium dioxide nanoparticles in fish cell lines. Ecotoxicology and Environmental Safety. 138: 309-319. DOI:10.1016/j.ecoenv.2016.12.039

Polloni-Silva J, Valdehita A, Fracácio R, Navas JM. 2017. Remediation efficiency of three treatments on water polluted with endocrine disruptors: Assessment by means of in vitro techniques. Chemosphere. 173: 267 – 274. DOI:10.1016/j.chemosphere.2017.01.029

Habila S, Leghouchi E, Valdehita A, Bermejo-Nogales A, Khelili S, Navas JM. 2017 Induction of EROD and BFCOD activities in tissues of barbel (Barbus callensis) from a water reservoir in Algeria Ecotoxicology and Environmental Safety. 142: 129-138. DOI: 10.1016/j.ecoenv.2017.03.055.

Toxicity of Contaminants

Coordinator / Coordinador

Jose María Navas Antón

Research Scientists / Científicos Titulares

María Luisa Fernández Cruz

Personal Laboral

Miguel Escario Pérez

Ingeniero de Montes

Alicia Soto

Azucena Bermejo Nogales

Judit Kalman

javier hernández

Verónica Serrano

Victor García Herranz

Contrato Predoctoral