PRECAUTION (PREdicting the Chemical sensitivity of AqUaTIc OrgaNism)

Samenvatting project

It is impossible and ethically undesirable to experimentally determine the sensitivity of all species present in rivers, lakes and streams everywhere around the world to all chemicals to which they can possibly be exposed. Therefore, a valuable method to help with the assessment environmental safety of chemicals is to extrapolate the known chemical sensitivity of species, for which toxicity has been determined, to species for which the toxicity is unknown. This method is also known as cross-species extrapolation of chemical sensitivity and is aimed at predicting the sensitivity of realistic species assemblages to chemicals. Creating a cross-species extrapolation modelling tool, flexible to different taxonomic and chemical groups, would allow for its incorporation into aquatic risk assessment, where it can assist in the protection of biodiversity.
Therefore, the two main objectives of this new project are: i) to transform an already existing cross-species extrapolation modelling framework into a userfriendly tool that can construct predictive models for multiple aquatic taxonomic and chemical groups, and ii) to deliver a set of case studies that demonstrate how this tool can directly be applied for aquatic water quality and risk assessment purposes.
We expect that this tool could be used to evaluate important modelling aspects for the application of trait and lineage-based models (e.g. exposure duration, effect endpoints), and facilitates their incorporation into ecological risk assessment.

Doel van het project

This project has two main objectives:
i) to transform the R pipeline developed by Van den Berg et al. (2019) into a user-friendly tool that can be applied to multiple aquatic taxonomic and chemical groups and can simultaneously be used to evaluate important modelling aspects for the application of trait- and lineage-based models, and
ii) to deliver a set of case studies and model validation studies that demonstrate how this tool can directly be applied for aquatic risk assessment purposes and to proof the validity of the constructed models.

To ensure that both objectives are addressed with equal importance the project is split into two separate phases. Phase 1 is concerned with objective i improving and evaluating the tool on both technical and scientific aspects whilst phase 2 is concerned with objective ii constructing case- and validation-studies that demonstrate the application and validity of the tool and the models for aquatic risk assessment purposes. The phases are subdivided into four working packages (WPs) which will be described in more detail in the section on ‘Geplande activiteiten’.

Motivatie

Since it is impossible to experimentally determine the sensitivity of all the species present in any ecosystem to all chemicals to which they can possibly be exposed we rely on cross-species extrapolation of chemical sensitivity. Such extrapolation requires on the one hand a mechanistic understanding of how a chemical can cause damage and on the other hand a mechanistic understanding of which factors cause that one species responds differently to a chemical than another species. Van den Berg et al. (2019) developed an R pipeline that provides predictive aquatic macro-invertebrate trait models for a diverse set of pre-defined Modes of Action (MOAs). This pipeline was later extended to also include relatedness-based predictors since other studies found that both traits and relatedness explained a unique part of sensitivity. Advantages of this pipeline include reproducibility (all analyses are 100% reproducible permitting clear communication of modelling decisions and outcomes) flexibility (the pipeline can be adjusted to different organism groups) and speed (models can be compiled in a few hours). However so far this R pipeline has been constructed for research purposes only and still requires fluency in R to make changes to its functionality and applicability. For instance adjusting the taxonomic focus of the models would require making changes in multiple parts of the R pipeline. Therefore further development of this pipeline by transforming it into a flexible tool would make it directly usable for incorporation into risk assessment and can additionally allow the assessment of important aspects influencing sensitivity models (e.g. exposure duration effect endpoints). Once the tool has been developed further and evaluated on important sensitivity modelling aspects the next step is to demonstrate how the tool can be applied in risk assessment.

Locatie

Wageningen

Uitgevoerde acties

1.1 Evaluation of model selection algorithms.
1.2 Transformation of R pipeline into a more user-friendly and flexible tool.
1.3 Evaluation of important sensitivity modelling aspects.
1.4 Tutorial on the new R tool.2.1 Collection of macroinvertebrate traits.

2.2 Improved macroinvertebrate models.
2.3 Selection of sensitivity-related fish traits.
2.4 Develop the first set of fish models.

3.1 First compilation of case-studies.
3.2 Workshop on case-studies.
3.3 Final compilation of case-studies.

4.1 Model validation with single species tests with invertebrates.
4.2 Data collection and model construction for non-lethal endpoints for invertebrates.

Verwachtte resultaten

1.1 User-friendly and flexible R tool.
1.2 Tutorial on the new R tool.
1.3 Journal publication(s) on the evaluation of important sensitivity modelling aspects.

2 Journal publication(s) on the improved tool using the macro-invertebrate and fish studies as examples.

3 Workshop publication(s) on case-studies.

4.1 Journal publication on the validation exercise.
4.2 Journal publication on the development of predictive models for non-lethal endpoints.

Innovativiteit

The main innovation of this project lies in the use and exploration of all toxicity data collected over time and the possibility to flexibly select evaluate and incorporate various important aspects of these data into statistical models. This combination of flexibility and big data will assist in obtaining new mechanistic information to understand the sensitivity process better which can strongly stimulate fundamental research into the ecological and chemical process of sensitivity as well as contribute to the transition to a zero animal-testing society.First we explain the activities performed under this project along with their type (industrial fundamental or experimental) and the role of the involved parties within these activities. Next we provide two tables containing more detailed information on the budget spend on each activity and a calculation of the percentage PPS financing.

Valorisatie

1.1 User-friendly and flexible R tool.
WENR, Unilever, other companies, risk assessors, regulators, policy makers will benefit from this tool.
The maintenance of the tool will lie with WENR (i.e. quarterly check on functionality and dependencies). Further development of the tool (i.e. incorporation of new functions) can be done by WENR if further funding will become available, but can also be picked up by any other party that is interested, since the tool will be published open and for free. Unilever will incorporate the tool in their risk assessment framework, and will help stimulate other companies to do the same.
1.2 Tutorial on the new R tool.
Anyone who will use the tool (see previous) will benefit from it. WENR, will check quarterly whether the tutorial and the tool are both still accessible and compatible with dependencies.
1.3 Journal publication on the evaluation of important sensitivity modelling aspects.
Scientists, risk assessors, regulators, modelers will benefit. Collaboration between WENR and Unilever. Usage is secured by open access publication.
2 Journal publication(s) on the improved tool, using the macroinvertebrate and fish studies as examples.
Scientists, risk assessors, regulators and modelers will benefit. Collaboration between WENR and Unilever. Usage is secured by open access publication.
3 Workshop publication on case-studies.
Scientists, risk assessors, regulators and modelers will benefit. Collaboration between WENR and Unilever. Usage is secured by open access publication.
4.1 Journal publication on the validation exercise.
Scientists, risk assessors, regulators and modelers will benefit. Main responsibility lies with WENR. Usage is secured by open access publication.
4.2 Journal publication on the development of predictive models for non-lethal endpoints for invertebrates.
Scientists, risk assessors, regulators and modelers will benefit. Main responsibility lies with WENR. Usage is secured by open access publication.

Hoe gaan de participanten van het project om met intellectueel eigendom dat voorkomt uit deze projecten?

1.1 WENR Open-source software, likely as R package or Shiny tool. Source-code will be made publicly available on github.
1.2 WENR As an Rmarkdown vignette, either inside the R package, and/or on a website.
1.3 WENR Open-access publication(s) in peer-reviewed journal.
2 WENR Open-access publication(s) in peer-reviewed journal.
3 WENR Open-access publication(s) in peer-reviewed journal.
4.1 WENR Open-access publication(s) in peer-reviewed journal.
4.2 WENR Open-access publication(s) in peer-reviewed journal.

Op welke wijze wordt de informatie over dit project op eenvoudige wijze voor het algemene publiek kenbaar gemaakt (beschrijving van het onderzoek, deelnemers en de planning en voortgang)?

We will publish basic project information on the website of the TKI Deltatechnology.
We will also construct our own website, on which we will post i) blogs on computational problems/solutions we come across during the project, ii) links to publications/other projects closely-related to the project, and iii) any news directly related to the project (e.g. publications produced by project partners, information on the planned workshop). We will publish a link to our website on the website of the TKI Deltatechnology.

Projectvoorwaarden

We will actively look for a direct collaboration with the Amsterdam eScience centre (https://www.esciencecenter.nl/collaborate/) for in-kind assistance with the computational structure of the project, and big data issues we expect to run into. We also expect to form some collaborations with other (trait-based) researchers, in order to obtain access to and assistance with state-of-the-art trait databases.
Also, we are open to any other partners, for instance policy makers, regulators, and other commercial companies. However, we will not actively look for them.

Projecteigenaar en projectleider(s)

Projecteigenaar:
Ir. J.A. (Arjan) Budding
Projectleider(s):
Prof. P.J. (Paul) van den Brink

Partners

  • Stichting Wageningen Research
  • TKI Deltatechnologie
  • Unilever, Safety &amp

Resultaten

PRECAUTION (PREdicting the Chemical sensitivity of AqUaTIc OrgaNism)-2023-4

Resultaat type
Tussentijds resultaat
Aantal
1
Omschrijving

The project is progressing satisfactorily, but the timeline and content of the deliverables have changed.

The content of the user-friendly and flexible R tool (deliverable 1) has changed. The development of predictive models for non-lethal endpoints (deliverable 7) required more time and effort than originally foreseen, and, in addition, required the development of an R package to support the data analysis of such a new and innovative endpoint (swimming behaviour). Therefore, the user-friendly and flexible R tool has resulted in the R package Kinematics. This R package comes with a manual and a vignette, which together constitute the tutorial on the new R tool (deliverable 2). We have also brought the application of this R tool one step further, by demonstrating how it can be used to study the swimming behaviour of the freshwater amphipod Gammarus pulex, and describing with experimental conditions should be kept in mind when studying such endpoints (deliverable 7). Finally, we applied the newly developed R tool to a risk assessment case study by exposing the test species Gammarus pulex to the antidepressant fluoxetine (deliverable 4).

The journal publication on the evaluation of important sensitivity modelling aspects (deliverable 3) has focused its scope on the statistical considerations required to construct predictive models for fish. This manuscript is still on its way, and it is foreseen that publication might go beyond the timeline of this project.

The workshop publication (deliverable 5) has also adjusted its scope according to the progress of the project, and focuses on (i) creating awareness on the pitfalls and shortcomings of currently used metrics for species sensitivity (ii) discussing what could be appropriate alternative descriptors of sensitivity, and (iii)
introducing a strategic roadmap with which novel metrics could achieve regulatory acceptance. Currently a first draft is about to be shared with the co-authors (i.e. workshop participants), and we foresee submission within the timeline of the project.

The experimental validation exercise (deliverable 6) did not deliver the insights we had foreseen (i.e. to validate the sensitivity models), but has instead brought valuable and generalizable insights into ecotoxicity testing. This manuscript now focuses on describing how the set-up of ecotoxicity tests can be improved to enhance the amount of information and understanding that can be obtained from them, and how the validity of ecotoxicity experiments can be improved. This deliverable will be submitted this month.

Finally, this project has made valuable contributions to two additional deliverables that were not foreseen at the start of the project:
- The development of criteria for reporting and evaluating ecotoxicity data (ETHOcred, submitted)
- A perspective paper that reviews and discusses how evolutionary conservation of pharmaceutical and personal care product targets can lead to an improved understanding of adverse outcomes across species and life stages (published)

Belangrijkste resultaten:
On the one hand, this project has led to the development of a new and innovative ecotoxicity endpoint, together with an easily appliable R tool. On the other hand, this project has become a pivotal center for valuable discussions and progress around the definition of species sensitivity in scientific and regulatory terms.

Wetenschappelijke publicatie?

PRECAUTION (PREdicting the Chemical sensitivity of AqUaTIc OrgaNism)-2022-2

Resultaat type
Tussentijds resultaat
Omschrijving

Het Precaution project vordert goed, met vooruitgang zichtbaar als (draft) producten in alle vier de werkpakketten en met nog voldoende budget beschikbaar om tot bruikbare eindproducten te komen. Vanwege capaciteitstekort is wel voorzien dat een aantal activiteiten van 2022 zal worden doorgeschoven naar volgend jaar (2023), waardoor de definitieve producten wat vertraagd zijn. Bij deze een overzicht van de uitgevoerde activiteiten, eventuele veranderingen, en (draft) producten van de vier werkpakketten:
- WP1 – Verbeteren van R tool: Binnen dit werkpakket is er al veel gebrainstormd over hoe de R tool er uit zal komen te zien, en zijn eerste stappen ondernomen om dit te implementeren. Daarbij zijn we tot inzicht gekomen dat de eerder opgezette format voor de tool te complex is om tot een toegankelijke en gebruikersvriendelijke tool te komen. Het idee is nu dat model-constructie binnen het project zal plaatsvinden (WP2), en dat de tool zal dienen om de resultaten van de verschillende modellen inzichtelijk te maken. Hierdoor moeten de definitieve modellen wel eerst beschikbaar zijn, waardoor deze activiteit is opgeschoven naar later in het project.
- WP2 – Nieuwe evertebrate- en vismodellen: Binnen dit werkpakket is een evertebrate-trait database aangevuld (P2), en zijn er nieuwe modellen ontwikkeld voor evertebraten (P4, P1). Daarnaast is er een overzicht gemaakt van de beschikbare vis-traits, en zijn de eerste vismodellen opgesteld (P3). De vismodellen laten veel potentie zien, en dit werk zal dus verder uitgewerkt worden tot een wetenschappelijke publicatie (P4). Daarnaast zullen alle modellen in de R tool verwerkt worden.
- WP3 – Workshop: Binnen dit werkpakket hebben discussies plaatsgevonden over de invulling van de workshop. Het idee zoals beschreven in het voorstel was om tijdens de workshop de R tool in verschillende case studies toe te passen. Echter zijn we tijdens het ontwikkelen van de R tool (WP1) en het maken van de nieuwe modellen (WP2), erachter gekomen dat de voornaamste problemen van onze modellen (en van de risicobeoordeling van chemicaliën in het algemeen) ligt in welke eenheid we gebruiken om gevoeligheid van organismen te beschrijven (P5). Momenteel wordt gevoeligheid namelijk beschreven door een over gesimplificeerde eenheid (de concentratie waarbij 50% van de individuen overlijdt, oftewel de LC50), terwijl het proces van gevoeligheid vele malen ingewikkelder is. Daarom zien we veel potentie om de workshop rondom dit onderwerp te concentreren, en hebben we de workshop verder uitgewerkt rondom dit idee (P6). Daarnaast zijn er, om ons project en deze kwestie internationaal op de kaart te zetten, verschillende communicatieactiviteiten uitgevoerd (P7 & P8).
- WP4 – Model-validatie en ontwikkeling nieuwe eindpunten: Binnen dit werkpakket heeft veel vooruitgang plaatsgevonden. We zijn nu bezig met de afronding van twee manuscripten omtrent het gebruik van gedragsstudies in de chemische risicobeoordeling. Daarnaast is er een R-package ontwikkeld en gepubliceerd die dergelijke gedrags-eindpunten kan berekenen aan de hand van de x- en y- positie van individuen over tijd.

Overzicht van de verschillende (draft) producten:
- P1 - Progress report on Toxicokinetic- toxicodynamic model fits for the chemical chlorpyrifos and imidacloprid
- P2 - Supplemented macroinvertebrate trait database, Marie-Claire Boerwinkel, Mirjam Tijhuis, Paul van den Brink, and Sanne van den Berg
- P3 - Student report 2021, Modelling the sensitivity of fishes to chemicals using traits. Arauxo Nicolas, Paul van den Brink, Frederik de Laender, and Sanne van den Berg
- P4 – Project update November 2021 (ppt), New fish and invertebrate trait models, Sanne van den Berg
- P5 – Project update January 2022 (ppt), The combined potential of species traits and mechanistic effect models, Sanne van den Berg
- P6 - Draft workshop invitation, Precaution workshop 13th and 14th of March 2023. Sanne van den Berg, Jan Baas, Claudia Rivetti, Bruno Campos, and Paul van den Brink
- P7 - Poster SETAC 2021, Precaution: Predicting the chemical sensitivity of aquatic organisms. Sanne van den Berg, Claudia Rivetti, Bruno Campos, and Paul van den Brink
- P8 - Session SETAC 2022, Bringing together exposure and effects: Towards a mechanistic understanding of species sensitivity. Sanne van den Berg, Andreas Focks, Caterina Zillien
- P9 - Draft manuscript, Among-individual variation in the swimming behaviour of the amphipod Gammarus pulex under dark and light conditions: implications for ecotoxicology. Sanne van den Berg, Pablo Rodríguez-Sánchez, Jiayu Zhao, Oluwafemi Olusoiji, Edwin Peeters, Lara Schuijt
- P10 - Draft manuscript, Large differences in the swimming behaviour of the amphipod Gammarus pulex due to experimental set-up due to antidepressant concentrations. Lara Schuijt, Asmita Dubey, Oluwafemi Olusoiji, Pablo Rodriguez-Sanchez, Rima Osman, Paul van den Brink, Sanne van den Berg
- P11 - R package 2021, Kinematics: Studying Sampled Trajectories., R, https://CRAN.R-project.org/package=kinematics. Rodriguez-Sanchez, P. ,Van den Berg, S.J.P.
- P12 - Poster SETAC 2021, How do behavioural endpoints relate to traditional endpoints? A big data approach. Sanne van den Berg, Joel Allen, and Jim Lazorchak

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