Nanotechnology and use of nanomaterials (NMs) improve life quality, economic growth and environmental health. However, the increasing production and use of NMs in commercial products has led to concerns about their potential toxicity on human and environment health, as well as its toxicological classification and regulation. In this context, there is an urgent need to standardize and validate procedures for nanotoxicity testing. Since the zebrafish embryotoxicity test (ZET) has been indicated as a suitable approach for the toxicity assessment of traditional and emergent pollutants, the aim of this review is to summarize the existing literature on embryotoxic and teratogenic effects of NMs on zebrafish. In addition, morphological changes in zebrafish embryos induced by NMs were classified in four reaction models, allowing classification of the mode of action and toxicity of different types of NM. Revised data showed that the interaction and bioaccumulation of NMs on zebrafish embryos were associated to several toxic effects, while the detoxification process was limited. In general, NMs induced delayed hatching, circulatory changes, pigmentation and tegumentary alterations, musculoskeletal disorders and yolk sac alterations on zebrafish embryos. Recommendations for nanotoxicological tests are given, including guidance for future research. This review reinforces the use of the ZET as a suitable approach to assess the health risks of NM exposure.

Embargo until 28 June 2021 | Nanotechnology and use of nanomaterials (NMs) improve life quality, economic growth and environmental health. However, the increasing production and use of NMs in commercial products has led to concerns about their potential toxicity on human and environment health, as well as its toxicological classification and regulation. In this context, there is an urgent need to standardize and validate procedures for nanotoxicity testing. Since the zebrafish embryotoxicity test (ZET) has been indicated as a suitable approach for the toxicity assessment of traditional and emergent pollutants, the aim of this review is to summarize the existing literature on embryotoxic and teratogenic effects of NMs on zebrafish. In addition, morphological changes in zebrafish embryos induced by NMs were classified in four reaction models, allowing classification of the mode of action and toxicity of different types of NM. Revised data showed that the interaction and bioaccumulation of NMs on zebrafish embryos were associated to several toxic effects, while the detoxification process was limited. In general, NMs induced delayed hatching, circulatory changes, pigmentation and tegumentary alterations, musculoskeletal disorders and yolk sac alterations on zebrafish embryos. Recommendations for nanotoxicological tests are given, including guidance for future research. This review reinforces the use of the ZET as a suitable approach to assess the health risks of NM exposure. | publishedVersion

Concentrations of organohalogenated contaminants (OHCs) can show significant temporal and spatial variation in the environment and wildlife. Most of the variation is due to changes in use and production, but environmental and biological factors may also contribute to the variation. Nestlings of top predators are exposed to maternally transferred OHCs in the egg and through their dietary intake after hatching. The present study investigated spatial and temporal variation of OHCs and the role of age and diet on these variations in plasma of Norwegian white-tailed eagle (Haliaeetus albicilla) nestlings. The nestlings were sampled at two locations, Smøla and Steigen, in 2015 and 2016. The age of the nestlings was recorded (range: 44 – 87 days old) and stable carbon and nitrogen isotopes (δ¹³C and δ¹⁵N) were applied as dietary proxies for carbon source and trophic position, respectively. In total, 14 polychlorinated biphenyls (PCBs, range: 0.82 – 59.05 ng/mL), 7 organochlorinated pesticides (OCPs, range: 0.89 – 52.19 ng/mL), 5 polybrominated diphenyl ethers (PBDEs, range: 0.03 – 2.64 ng/mL) and 8 perfluoroalkyl substances (PFASs, range: 4.58 – 52.94 ng/mL) were quantified in plasma samples from each location and year. The OHC concentrations, age and dietary proxies displayed temporal and spatial variations. The age of the nestlings was indicated as the most important predictor for OHC variation as the models displayed significantly decreasing plasma concentrations of PCBs, OCPs, and PBDEs with increasing age, while concentrations of PFASs were significantly increasing with age. Together with age, the variations in PCB, OCP and PBDE concentrations were also explained by δ¹³C and indicated decreasing concentrations with a more marine diet. Our findings emphasise age and diet as important factors to consider when investigating variations in plasma OHC concentrations in nestlings.

peer reviewed | Concentrations of organohalogenated contaminants (OHCs) can show significant temporal and spatial variation in the environment and wildlife. Most of the variation is due to changes in use and production, but environmental and biological factors may also contribute to the variation. Nestlings of top predators are exposed to maternally transferred OHCs in the egg and through their dietary intake after hatching. The present study investigated spatial and temporal variation of OHCs and the role of age and diet on these variations in plasma of Norwegian white-tailed eagle (Haliaeetus albicilla) nestlings. The nestlings were sampled at two locations, Smøla and Steigen, in 2015 and 2016. The age of the nestlings was recorded (range: 44 – 87 days old) and stable carbon and nitrogen isotopes (δ13C and δ15N) were applied as dietary proxies for carbon source and trophic position, respectively. In total, 14 polychlorinated biphenyls (PCBs, range: 0.82 – 59.05 ng/mL), 7 organochlorinated pesticides (OCPs, range: 0.89 – 52.19 ng/mL), 5 polybrominated diphenyl ethers (PBDEs, range: 0.03 – 2.64 ng/mL) and 8 perfluoroalkyl substances (PFASs, range: 4.58 – 52.94 ng/mL) were quantified in plasma samples from each location and year. The OHC concentrations, age and dietary proxies displayed temporal and spatial variations. The age of the nestlings was indicated as the most important predictor for OHC variation as the models displayed significantly decreasing plasma concentrations of PCBs, OCPs, and PBDEs with increasing age, while concentrations of PFASs were significantly increasing with age. Together with age, the variations in PCB, OCP and PBDE concentrations were also explained by δ13C and indicated decreasing concentrations with a more marine diet. Our findings emphasise age and diet as important factors to consider when investigating variations in plasma OHC concentrations in nestlings. © 2018 Elsevier Ltd | 230465

Concentrations of organohalogenated contaminants (OHCs) can show significant temporal and spatial variation in the environment and wildlife. Most of the variation is due to changes in use and production, but environmental and biological factors may also contribute to the variation. Nestlings of top predators are exposed to maternally transferred OHCs in the egg and through their dietary intake after hatching. The present study investigated spatial and temporal variation of OHCs and the role of age and diet on these variations in plasma of Norwegian white-tailed eagle (Haliaeetus albicilla) nestlings. The nestlings were sampled at two locations, Smøla and Steigen, in 2015 and 2016. The age of the nestlings was recorded (range: 44 - 87 days old) and stable carbon and nitrogen isotopes (δ13C and δ15N) were applied as dietary proxies for carbon source and trophic position, respectively. In total, 14 polychlorinated biphenyls (PCBs, range: 0.82 - 59.05 ng/mL), 7 organochlorinated pesticides (OCPs, range: 0.89 - 52.19 ng/mL), 5 polybrominated diphenyl ethers (PBDEs, range: 0.03 - 2.64 ng/mL) and 8 perfluoroalkyl substances (PFASs, range: 4.58 - 52.94 ng/mL) were quantified in plasma samples from each location and year. The OHC concentrations, age and dietary proxies displayed temporal and spatial variations. The age of the nestlings was indicated as the most important predictor for OHC variation as the models displayed significantly decreasing plasma concentrations of PCBs, OCPs, and PBDEs with increasing age, while concentrations of PFASs were significantly increasing with age. Together with age, the variations in PCB, OCP and PBDE concentrations were also explained by δ13C and indicated decreasing concentrations with a more marine diet. Our findings emphasise age and diet as important factors to consider when investigating variations in plasma OHC concentrations in nestlings. | acceptedVersion

Despite the abundant literature on the adverse effects of Bisphenol A (BPA) as endocrine disruptor, its toxicity mechanisms are still poorly understood. We present here a study of its effects on the zebrafish eleutheroembryo transcriptome at concentrations ranging from 0.1 to 4 mg L⁻¹, this latter representing the lowest observed effect concentration (LOEC) found in our study at three different macroscopical endpoints (survival, hatching and swim bladder inflation). Multivariate data analysis methods identified both monotonic and bi-phasic patterns of dose-dependent responses. Functional analyses of genes affected by BPA exposure suggest an interaction of BPA with different signaling pathways, being the estrogenic and retinoid receptors two likely targets. In addition, we identified an apparently unrelated inhibitory effect on, among others, visual function genes. We interpret our data as the result of a sum of underlying, independent molecular mechanisms occurring simultaneously at the exposed animals, well below the macroscopic LOEC, but related to at least some of the observed morphological alterations, particularly in eye size and yolk sac resorption. Our data supports the idea that the physiological effects of BPA cannot be only explained by its rather weak interaction with the estrogen receptor, and that multivariate analyses are required to analyze the effects of toxicants like BPA, which interact with different cellular targets producing complex phenotypes.

Despite the abundant literature on the adverse effects of Bisphenol A (BPA) as endocrine disruptor, its toxicity mechanisms are still poorly understood. We present here a study of its effects on the zebrafish eleutheroembryo transcriptome at concentrations ranging from 0.1 to 4 mg L−1, this latter representing the lowest observed effect concentration (LOEC) found in our study at three different macroscopical endpoints (survival, hatching and swim bladder inflation). Multivariate data analysis methods identified both monotonic and bi-phasic patterns of dose-dependent responses. Functional analyses of genes affected by BPA exposure suggest an interaction of BPA with different signaling pathways, being the estrogenic and retinoid receptors two likely targets. In addition, we identified an apparently unrelated inhibitory effect on, among others, visual function genes. We interpret our data as the result of a sum of underlying, independent molecular mechanisms occurring simultaneously at the exposed animals, well below the macroscopic LOEC, but related to at least some of the observed morphological alterations, particularly in eye size and yolk sac resorption. Our data supports the idea that the physiological effects of BPA cannot be only explained by its rather weak interaction with the estrogen receptor, and that multivariate analyses are required to analyze the effects of toxicants like BPA, which interact with different cellular targets producing complex phenotypes. Estrogenic- and retinoid-like transcriptomic effects of bisphenol A in zebrafish eleutheroembryos and their relationship with morphological alterations. © 2018 Elsevier Ltd | This work was supported by the European Research Council under the European Union's Seventh Framework Programme ( FP/2007–2013 )/ERC Grant Agreement n. 320737 . Some part of this study was also supported by a grant from the Spanish Ministry of Economy and Competitiveness ( CTQ2014-56777-R ) and by a grant ( PT17/0009/0019 ) from ISCIII (Carlos III Health Institute), part of the Spanish Ministry of Economy and Competitiveness, and cofinanced by the European Regional Development Fund (ERDF). LNM was supported by a Beatriu de Pinos Postdoctoral Fellow ( 2013BP-B-00088 ) awarded by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the Cofund programme of the Marie Curie Actions of the 7th R&D Framework Programme of the European Union. RM was supported by a FPU predoctoral fellow from the Spanish Ministry of Education, Culture and Sport (ref. FPU15/03332 ). We would like to thank Ms. Elia Martinez-Prats and David Angelats for helping with the real time qRT-PCRs measurements. Appendix A | Peer reviewed