title: Early life exposure to PCB126 results in delayed mortality and growth impairment in the zebrafish larvae.
abstract: The occurrence of chronic or delayed toxicity resulting from the exposure to sublethal chemical concentrations is an increasing concern in environmental risk assessment. The Fish Embryo Toxicity (FET) test with zebrafish provides a reliable prediction of acute toxicity in adult fish, but it cannot yet be applied to predict the occurrence of chronic or delayed toxicity. Identification of sublethal FET endpoints that can assist in predicting the occurrence of chronic or delayed toxicity would be advantageous. The present study characterized the occurrence of delayed toxicity in zebrafish larvae following early exposure to PCB126, previously described to cause delayed effects in the common sole. The first aim was to investigate the occurrence and temporal profiles of delayed toxicity during zebrafish larval development and compare them to those previously described for sole to evaluate the suitability of zebrafish as a model fish species for delayed toxicity assessment. The second aim was to examine the correlation between the sublethal endpoints assessed during embryonal and early larval development and the delayed effects observed during later larval development. After exposure to PCB126 (3-3000ng/L) until 5 days post fertilization (dpf), larvae were reared in clean water until 14 or 28 dpf. Mortality and sublethal morphological and behavioural endpoints were recorded daily, and growth was assessed at 28 dpf. Early life exposure to PCB126 caused delayed mortality (300 ng/L and 3000 ng/L) as well as growth impairment and delayed development (100 ng/L) during the clean water period. Effects on swim bladder inflation and cartilaginous tissues within 5 dpf were the most promising for predicting delayed mortality and sublethal effects, such as decreased standard length, delayed metamorphosis, reduced inflation of swim bladder and column malformations. The EC50 value for swim bladder inflation at 5 dpf (169 ng/L) was similar to the LC50 value at 8 dpf (188 and 202 ng/L in two experiments). Interestingly, the patterns of delayed mortality and delayed effects on growth and development were similar between sole and zebrafish. This indicates the comparability of critical developmental stages across divergent fish species such as a cold water marine flatfish and a tropical freshwater cyprinid. Additionally, sublethal effects in early embryo-larval stages were found promising for predicting delayed lethal and sublethal effects of PCB126. Therefore, the proposed method with zebrafish is expected to provide valuable information on delayed mortality and delayed sublethal effects of chemicals and environmental samples that may be extrapolated to other species.
authors.affiliation: Swiss Centre for Applied Ecotoxicology Eawag-EPFL, 8600, Dübendorf, Switzerland; Department of Ecosystem Analysis, Institute for Environmental Research, RWTH Aachen University, 52074, Aachen, Germany. Electronic address: carolina.dipaolo@bio5.rwth-aachen.de.
authors.forename: Carolina
authors.initials: C
authors.lastname: Di Paolo
authors.affiliation: Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600, Dübendorf, Switzerland; ETH Zürich, Department of Chemistry and Applied Biosciences, 8093 Zürich, Switzerland. Electronic address: ksenia.groh@eawag.ch.
authors.forename: Ksenia J
authors.initials: KJ
authors.lastname: Groh
authors.affiliation: Empa, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Advanced Analytical Technologies, 8600, Dübendorf, Switzerland. Electronic address: markus.zennegg@empa.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Zennegg
authors.affiliation: Swiss Centre for Applied Ecotoxicology Eawag-EPFL, 8600, Dübendorf, Switzerland. Electronic address: etienne.vermeirssen@oekotoxzentrum.ch.
authors.forename: Etiënne L M
authors.initials: EL
authors.lastname: Vermeirssen
authors.affiliation: Wageningen University, Marine Animal Ecology Group, 6708WD, Wageningen, The Netherlands; IMARES, Institute for Marine Resources and Ecosystem Studies, Wageningen UR, 1780 AB, Den Helder, The Netherlands. Electronic address: tinka.murk@wur.nl.
authors.forename: Albertinka J
authors.initials: AJ
authors.lastname: Murk
authors.affiliation: Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600, Dübendorf, Switzerland; ETH Zürich, Department of Environmental Systems Science, 8092 Zürich, Switzerland. Electronic address: rik.eggen@eawag.ch.
authors.forename: Rik I L
authors.initials: RI
authors.lastname: Eggen
authors.affiliation: Department of Ecosystem Analysis, Institute for Environmental Research, RWTH Aachen University, 52074, Aachen, Germany. Electronic address: henner.hollert@bio5.rwth-aachen.de.
authors.forename: Henner
authors.initials: H
authors.lastname: Hollert
authors.affiliation: Swiss Centre for Applied Ecotoxicology Eawag-EPFL, 8600, Dübendorf, Switzerland. Electronic address: inge.werner@oekotoxzentrum.ch.
authors.forename: Inge
authors.initials: I
authors.lastname: Werner
authors.affiliation: Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600, Dübendorf, Switzerland; ETH Zürich, Department of Environmental Systems Science, 8092 Zürich, Switzerland; EPF Lausanne, School of Architecture, Civil and Environmental Engineering, 1015 Lausanne, Switzerland. Electronic address: kristin.schirmer@eawag.ch.
authors.forename: Kristin
authors.initials: K
authors.lastname: Schirmer
mesh_terms: D000400:Air Sacs / Q000187:drug effects; D000818:Animals; D047108:Embryonic Development / Q000187:drug effects*; D007928:Lethal Dose 50; D009026:Mortality; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology / Q000502:physiology*
chemical_list: D014874:Water Pollutants, Chemical; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl
keywords: Delayed effects; Early life stages; Growth; PCB126; Sublethal effects; Zebrafish