Manufactured nanoparticle bioavailability and environmental exposure (nanoBEE)
Lead Research Organisation:
University of Exeter
Department Name: Biosciences
Abstract
The nano-BEE consortia will develop and refine, using empirical data, a critical subset of models focused on exposure to nanomaterials (NMs) and their bioavailability in the environment. The objectives of this study are to (a) generate controlled and well-characterized NMs libraries for environmental assessment (b) prove that soft landed gold clusters provide suitable fiducial markers to enable angstrom resolution in aquatic tomography of NMs in environmental media (c) demonstrate that NM environmental modification processes can be classified by the extent of aggregation, dissolution and surface modification and to experimentally and computationally describe the partition of these modified NMs between environmental compartments (d) to develop modified biodynamic models for NM bioavailability that reflect both water and food exposures and (e) to validate biotic ligand models for NM effects on aquatic organisms. An integrated computational and experimental program will examine the environmental chemistry of manufactured NMs using electron microscopy, scattering techniques, and spectroscopy; use traceable NMs to quantify influx and efflux rates in model aquatic species, including in a trophic chain; and employ both conventional measures of toxicological endpoints as well as the latest molecular ('omics') methods to quantify biological effects as well as identify new mechanisms for toxicity. Such information will be input into biotic ligand models for NMs classes that output anticipated EC50 and other outcomes given information about NM exposure and local water chemistry. Through its engagement with end-users the consortia will link its predictions of NM body burdens and toxicological outcomes to risk management frameworks useful in regulatory decision-making.
Publications
Baalousha M
(2012)
Characterization of cerium oxide nanoparticles-part 2: nonsize measurements.
in Environmental toxicology and chemistry
Baalousha M
(2012)
Characterization of cerium oxide nanoparticles-part 1: size measurements.
in Environmental toxicology and chemistry
Cross R
(2015)
Transformations that affect fate, form and bioavailability of inorganic nanoparticles in aquatic sediments
in Environmental Chemistry
Dogra Y
(2016)
Cerium oxide nanoparticles induce oxidative stress in the sediment-dwelling amphipod Corophium volutator.
in Nanotoxicology
Dylan L. Windell
The influence of size and surface chemistry on bioavailability, tissue targets, and toxicity of gold nanoparticles in zebrafish (Danio Rerio): Implications for a potential environmental impact
in Ecotoxicology and Environmental Safety
Fabrega J
(2012)
Sequestration of zinc from zinc oxide nanoparticles and life cycle effects in the sediment dweller amphipod Corophium volutator.
in Environmental science & technology
Galloway T
(2017)
Ecotoxicological assessment of nanoparticle-containing acrylic copolymer dispersions in fairy shrimp and zebrafish embryos
in Environmental Science: Nano
Gillies S
(2022)
Transgenic zebrafish larvae as a non-rodent alternative model to assess pro-inflammatory (neutrophil) responses to nanomaterials.
in Nanotoxicology
| Description | We have investigated the toxicological properties of Ag and TiO2, including for Ag assessing the effects of coatings in the zebrafish embryos and early life stages as our experimental model. The work includes the application of advanced imaging methods including CARS. We provide evidence that the toxicological properties of silver MNPs largely relates to the release of silver ions. We built on this work to develop and apply whole mount in situ hybrisidation as approach in the zebrafish to assess for exposure effects to silver NMs compared with bulk counterparts. In this work we have developed significant information on the ontogeny of expression of a suite of genes that are involved in detoxification and oxidative stress and tissue specific responses to the silver materials. We applied whole mount in-situ hybridisation (WISH) in zebrafish embryos and larvae for a suite of genes involved with detoxifying processes and oxidative stress, including metallothionein (mt2), glutathionine S-transferase pi (gstp), glutathionine S-transferase mu (gstm1), heme oxygenase (hmox1) and ferritin heavy chain 1 (fth1) to identify potential target tissues and effect mechanisms of AgNPs compared with a bulk counterpart and ionic silver (AgNO3). AgNPs caused upregulation in the expression of mt2, gstp and gstm1 and down regulation of expression of both hmox1 and fth1 and there were both life stage and tissue specific responses. Responding tissues included olfactory bulbs, lateral line neuromasts, and ionocytes in the skin with the potential for effects on olfaction, behaviour, and maintenance of ion balance. Silver ions induced similar gene responses and affected the same target tissues as AgNPs. AgNPs invoked levels of target gene responses more similar to silver treatments compared with coated AgNPs indicating the responses seen were due to released silver ions. In the Nrf2 zebrafish mutant, expression of mt2 (24 hpf) and gstp (3 dpf) were either non-detectable or were at lower levels compared with wild type zebrafish for exposures to AgNPs, indicating that these gene responses are controlled through the Nrf2-Keap pathway. This work is now submitted for publication to Nanotoxicology. We have further used the zebrafish model (embryos) and transcriptomics to analyses the genome wide response to silver materials (nanos and bulk and ionic) to again show that the main effects on the nanomaterial are as a function of silver ions (published in vanAerle et al.,2013). Working with Imperial University, University of Birmingham the Natural History Museum and US Geological Survey we have undertaken exposures of zebrafish to isotopically labelled nanomaterials to investigate for effects for exposures at concentrations with environmental relevance. In addition in zebrafish we have also conducted a long term exposure to silver MNPs and a bulk counterpart via the diet to assess effects on reproduction. We have also then assessed for effects of parental exposure to these material on the offspring including assessing for effects on responses of genes involved with metal handing and oxidative stress. For the dosing we adopted (20ug/g body weight) we found no effects on egg production, but we appear to be seeing differences in gene expression of mt2 in the offspring in their responsiveness to silver. This is a novel finding and through EU funding we are now undertaking a major transgenerational study to look at the epigenetic mechanisms for the effects seen. We have undertaken a pilot study exposure and a longer term exposure of Xenotoca to silver materials exposed via the diet to assess for transfer to the offspring and health effects in those offspring. The pilot data indicated a higher level of silver in offspring in the adult fish fed silver MNMs compared with the bulk counterpart. A second exposure of Xenotoca has now been completed to compare silver NMs (7nm) with different coatings, (citrate and PVP), via the diet (adopting the same approach as for the previous experiment). This study has also included a depuration period for the fry. The idea for this study is to see whether coating has an effect on the bioavailability of the MNM/silver in the exposed adults and subsequent developing offspring and whether there are effects of the exposures on the subsequent offspring. All tissue samples for ICP-MS have been analysed and biological effects have been measured. This work forms major part of a PhD thesis (NERC funded) - Victoria Jennings due for completion in 2017. Three further research papers are in preparation from the above work. |
| Exploitation Route | This imaging method we have applied to asses nanomaterial uptake into biological tissue (CARS microscopy) and whole mount in situ hybrisidation) used to assess for exposure (effects for nanomaterials in fish embrys/intact fish are now being adopted in other laboratories for nanomaterial research and indeed have much wider utility for studies on toxicants more generally. Our new fish model potentially provides an alternative model to rodents for studies into maternal transfer of toxicants. |
| Sectors | Chemicals,Communities and Social Services/Policy,Education,Environment,Government, Democracy and Justice,Manufacturing, including Industrial Biotechology |
| Description | We have applied zebrafish embryos to study the toxicological properties of a range metal based nanomaterials and shown that of those tested, with the exception of silver, none were toxic for any concentrations that bear any environmental relevance. These data are of significance in assessing the toxicological risk for these nanomaterials in the environment. This project had advanced the use of imaging methods (CARS microscopy and whole mount in situ hybrisidation) to assess for exposure (bioavailability) and effects to nanomaterials that are now being adopted widely in other laboratories for nanomaterial research. Through the application of transcriptomics to analyses the genome wide responses in zebrafish embryos , we show that the main effects for silver nanoparticles are a function of silver ions (i.e. ion dissolution) and not the physical nature of the particle. These data support the building consensus that the toxicity for silver nanomaterials derives from silver ions, with significant implications for risk analyses of metal nanomaterials. We have provided preliminary evidence for transgeneration effects for exposure to silver nanoparticles with altered responses in the next generation to silver toxicity. This will have a significant bearing on risk assessments for this nanomaterial. We have developed a new fish model for studies into maternal transfer of nanomaterials in a live bearing fish (Xenotoca) with potential application to toxicants more generally. This research has lead to further significant research projects on nanomaterials funded by EU (540k Euros, part of a £9M Consortium grant), NERC (£795k), partnering with the Universities of Birmingham and Imperial) and industry (BASF),investigating the ecotoxicology of nanopolymer dispersions. Through this research project, partnerships have also been established with Nanomaterials Industry Association, the OECD, the Natural History Museum, and US Geological Survey, and Tyler has become a (funded) Consultant for a German National programme on Nanomaterials (2013-2017). The post doctoral researcher on this grant obtained a full time position as a science writer. |
| First Year Of Impact | 2012 |
| Sector | Creative Economy,Education,Environment,Manufacturing, including Industrial Biotechology |
| Impact Types | Cultural,Societal,Economic |
| Description | EU Commission |
| Geographic Reach | Europe |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | This research project has contributed to the validation process for use of transgenic zebrafish in a new OECD guideline test protocol, in a collaboration developed with Dr Francois Brion , INERIS, France.. |
| Description | 2014-17. BBSRC Industrial CASE studentship with AstraZeneca(PhD - Dylan Windell). Tracing nanodrugs in aquatic organisms using light sheet microscopy. |
| Amount | £80,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | BASF Ecotoxicology of nanopolymer dispersions. A case study of aqueous acrylic ester copolymers |
| Amount | £144,000 (GBP) |
| Organisation | BASF |
| Sector | Private |
| Country | Germany |
| Start | |
| Description | German Government - Consultant for National programme on Nanomaterials |
| Amount | € 50,000 (EUR) |
| Organisation | Government of Germany |
| Sector | Public |
| Country | Germany |
| Start | |
| Description | GuideNano: Assessment and mitigation of nano-enabled product risks on human and environmental health |
| Amount | € 139,000 (EUR) |
| Funding ID | 604387 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | |
| Description | NERC (£1M consortium, with University of Birmingham and CEH) Nanomaterial transformations: Implications for metrology and ecotoxicology in natural systems. |
| Amount | £330,000 (GBP) |
| Funding ID | NE/N006178/1 |
| Organisation | Natural Environment Research Council |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | NERC (Exeter, Birmingham and Imperial). Metal/Metal Oxide Nanoparticles and Oxidative Stress - Are there Harmful Health Effects in Fish for Environmental Exposures? |
| Amount | £795,000 (GBP) |
| Funding ID | NE/L007371/1 |
| Organisation | Natural Environment Research Council |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | NanoMILE |
| Amount | € 540,000 (EUR) |
| Funding ID | 310451 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | |
| Description | PATROLS EU consortium |
| Amount | £9,000,000 (GBP) |
| Organisation | European Commission |
| Department | Horizon 2020 |
| Sector | Public |
| Country | European Union (EU) |
| Start | 11/2017 |
| End | 10/2021 |
| Title | Developed a new experimental fish model (Xenotoca) for studies investigating maternal transfer of nanomaterials. |
| Description | Developed a new experimental fish model (Xenotoca) for studies investigating maternal transfer of nanomaterials. |
| Type Of Material | Technology assay or reagent |
| Provided To Others? | No |
| Impact | n/a |
| Title | Development of in situ hybridization for visualizing responses to metal nanomaterials in whole zebrafish embryos and early life stage. |
| Description | Development of in situ hybridization for visualizing responses to metal nanomaterials in whole zebrafish embryos and early life stage. |
| Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
| Year Produced | 2015 |
| Provided To Others? | Yes |
| Impact | Development of in situ hybridization for visualizing responses to metal nanomaterials in whole zebrafish embryos and early life stage. |
| Title | Initiated studies into the development of transgenic fish for studies into the effects of nanoparticles via oxidative stress mechanisms. |
| Description | Initiated studies into the development of transgenic fish for studies into the effects of nanoparticles via oxidative stress mechanisms. |
| Type Of Material | Technology assay or reagent |
| Provided To Others? | No |
| Impact | n/a |
| Title | Tools for investigating Nanomaterials |
| Description | • Advancement of use of isotopic methods (Universities of Birmingham and Imperial) for studies into the ecotoxicology of nanomaterials. • Development of in situ hybridization for visualizing responses to metal nanomaterials in whole zebrafish embryos and early life stage ( paper submitted for publication in Nanotoxicology). • Developed a new experimental fish model (Xenotoca) for studies investigating maternal transfer of nanomaterials (2 papers on this model are in preparation for publication) |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2017 |
| Provided To Others? | Yes |
| Impact | N/A |
| Description | Enivornment Agency - partner on NERC grant |
| Organisation | Meteorological Office UK |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | UK Environment Agency |
| Collaborator Contribution | partner on recent NERC funded grant |
| Impact | Research papers and government reports |
| Description | PATROLS |
| Organisation | Heriot-Watt University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have forged strong research partnerships with the Universities of Birmingham, Imperial, Herriott Watt, and CEH for research into the ecotoxicology of nanomaterials, which has led to significant further funding from the EU, NERC and NC3Rs, reported in the 2016 return and also the following grant in 2017: • Development of in situ hybridization for visualizing responses to metal nanomaterials in whole zebrafish embryos and early life stage ( paper submitted for publication in Nanotoxicology). • Developed a new experimental fish model (Xenotoca) for studies investigating maternal transfer of nanomaterials (2 papers on this model are in preparation for publication) |
| Collaborator Contribution | Advancement of use of isotopic methods (Universities of Birmingham and Imperial) for studies into the ecotoxicology of nanomaterials. PATROLS - An EU consortium. The Impacts of Manufactured Nanomaterials on Natural Systems (€590 000 to Exeter, £9M overall proposal). |
| Impact | 3 papers have been submitted. The EpRE transgenic fish model developed in this project has being used as part of a wider battery of transgenic zebrafish models developed at Exeter to a further research collaboration with AstraZeneca: Drug Safety Assay Development Research (£252k), which follows-on from a previous consultancy agreement. The majority of this project aims to evaluate the potential for transgenic zebrafish models to aid the prediction of human side effects of pharmaceuticals. |
| Start Year | 2017 |
| Description | PATROLS |
| Organisation | Imperial College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have forged strong research partnerships with the Universities of Birmingham, Imperial, Herriott Watt, and CEH for research into the ecotoxicology of nanomaterials, which has led to significant further funding from the EU, NERC and NC3Rs, reported in the 2016 return and also the following grant in 2017: • Development of in situ hybridization for visualizing responses to metal nanomaterials in whole zebrafish embryos and early life stage ( paper submitted for publication in Nanotoxicology). • Developed a new experimental fish model (Xenotoca) for studies investigating maternal transfer of nanomaterials (2 papers on this model are in preparation for publication) |
| Collaborator Contribution | Advancement of use of isotopic methods (Universities of Birmingham and Imperial) for studies into the ecotoxicology of nanomaterials. PATROLS - An EU consortium. The Impacts of Manufactured Nanomaterials on Natural Systems (€590 000 to Exeter, £9M overall proposal). |
| Impact | 3 papers have been submitted. The EpRE transgenic fish model developed in this project has being used as part of a wider battery of transgenic zebrafish models developed at Exeter to a further research collaboration with AstraZeneca: Drug Safety Assay Development Research (£252k), which follows-on from a previous consultancy agreement. The majority of this project aims to evaluate the potential for transgenic zebrafish models to aid the prediction of human side effects of pharmaceuticals. |
| Start Year | 2017 |
| Description | PATROLS |
| Organisation | UK Centre for Ecology & Hydrology |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | We have forged strong research partnerships with the Universities of Birmingham, Imperial, Herriott Watt, and CEH for research into the ecotoxicology of nanomaterials, which has led to significant further funding from the EU, NERC and NC3Rs, reported in the 2016 return and also the following grant in 2017: • Development of in situ hybridization for visualizing responses to metal nanomaterials in whole zebrafish embryos and early life stage ( paper submitted for publication in Nanotoxicology). • Developed a new experimental fish model (Xenotoca) for studies investigating maternal transfer of nanomaterials (2 papers on this model are in preparation for publication) |
| Collaborator Contribution | Advancement of use of isotopic methods (Universities of Birmingham and Imperial) for studies into the ecotoxicology of nanomaterials. PATROLS - An EU consortium. The Impacts of Manufactured Nanomaterials on Natural Systems (€590 000 to Exeter, £9M overall proposal). |
| Impact | 3 papers have been submitted. The EpRE transgenic fish model developed in this project has being used as part of a wider battery of transgenic zebrafish models developed at Exeter to a further research collaboration with AstraZeneca: Drug Safety Assay Development Research (£252k), which follows-on from a previous consultancy agreement. The majority of this project aims to evaluate the potential for transgenic zebrafish models to aid the prediction of human side effects of pharmaceuticals. |
| Start Year | 2017 |
| Description | PATROLS |
| Organisation | University of Birmingham |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have forged strong research partnerships with the Universities of Birmingham, Imperial, Herriott Watt, and CEH for research into the ecotoxicology of nanomaterials, which has led to significant further funding from the EU, NERC and NC3Rs, reported in the 2016 return and also the following grant in 2017: • Development of in situ hybridization for visualizing responses to metal nanomaterials in whole zebrafish embryos and early life stage ( paper submitted for publication in Nanotoxicology). • Developed a new experimental fish model (Xenotoca) for studies investigating maternal transfer of nanomaterials (2 papers on this model are in preparation for publication) |
| Collaborator Contribution | Advancement of use of isotopic methods (Universities of Birmingham and Imperial) for studies into the ecotoxicology of nanomaterials. PATROLS - An EU consortium. The Impacts of Manufactured Nanomaterials on Natural Systems (€590 000 to Exeter, £9M overall proposal). |
| Impact | 3 papers have been submitted. The EpRE transgenic fish model developed in this project has being used as part of a wider battery of transgenic zebrafish models developed at Exeter to a further research collaboration with AstraZeneca: Drug Safety Assay Development Research (£252k), which follows-on from a previous consultancy agreement. The majority of this project aims to evaluate the potential for transgenic zebrafish models to aid the prediction of human side effects of pharmaceuticals. |
| Start Year | 2017 |
| Description | University of Birmingham/Imperial College London |
| Organisation | Heriot-Watt University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have forged strong research partnerships with the Universities of Birmingham and Imperial for research into the ecotoxicology of nanomaterials , which has led to significant further funding (EU and NERC). |
| Collaborator Contribution | as above |
| Impact | n/a |
| Start Year | 2011 |
| Description | University of Birmingham/Imperial College London |
| Organisation | Imperial College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have forged strong research partnerships with the Universities of Birmingham and Imperial for research into the ecotoxicology of nanomaterials , which has led to significant further funding (EU and NERC). |
| Collaborator Contribution | as above |
| Impact | n/a |
| Start Year | 2011 |
| Description | University of Birmingham/Imperial College London |
| Organisation | University of Birmingham |
| Department | School of Geography, Earth and Environmental Sciences |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have forged strong research partnerships with the Universities of Birmingham and Imperial for research into the ecotoxicology of nanomaterials , which has led to significant further funding (EU and NERC). |
| Collaborator Contribution | as above |
| Impact | n/a |
| Start Year | 2011 |
| Description | Invited Opening Keynote Speech for international society for the Developmental Origins of Health and Disease, Melbourne , Australia |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The Chemical Environment and Health. International Society for the Developmental Origins of Health and Disease, Melbourne , Australia, Invited Opening Keynote 22nd October 2019 |
| Year(s) Of Engagement Activity | 2019 |