Tjalling Jager

DEBtox Research

The paper is available through Open Access: http://link.springer.com/article/10.1007%2Fs00227-016-3030-8 Mechanistic models are essential tools for interpreting and predicting the consequences of a changing environment and stressors such as pollution on the life histories of marine organisms. Here, we apply the simple and generic energy-budget mod...

The ongoing global climate crisis increases temperatures in polar regions faster and with greater magnitude than elsewhere. The decline of Arctic sea ice opens up new passages, eventually leading to higher anthropogenic activities such as shipping, fishing, and mining. Climate change and anthropogenic activities will increase contaminant transport...

Mechanistic effect models have become increasingly popular for use in the frame of the environmental risk assessment of plant protection products and the active substances therein (summarized as pesticides). In 2018, the EFSA Panel on Plant Protection Products and their Residues (PPR) considered TKTD models of the GUTS family. fit for the modelling...

The prevalence of standardized toxicity testing in ecotoxicology has largely obscured the notion that toxicity is a function of time as well. The necessity of considering time is vividly demonstrated by observations of delayed mortality, that is, deaths continue to occur even when animals are no longer exposed to a toxicant. In this contribution, I...

The extrapolation of effects from controlled standard laboratory tests to real environmental conditions is a major challenge facing Ecological Risk Assessment (ERA) of chemicals. Toxicokinetic‐Toxicodynamic (TKTD) models, such as those based on Dynamic Energy Budget (DEB) theory, can play an important role in filling this gap. Through the years, di...

This e-book is available for download (also for free) at: Leanpub: https://leanpub.com/debtox_book. The full text here only provides the first 15 pages of the book. The first version was published on 9 April 2012, and several updates have occurred since. ABSTRACT. Have you ever asked yourself why the effects of toxic chemicals depend on the expos...

The full book is available for download here: https://leanpub.com/guts_book . What you see on Rresearch Gate as download is a sample (the first 15 pages). The first release of this book was on 18 January 2018, but several updates have occurred since. ABSTRACT. Stressors, such as toxicants, can cause mortality among organisms. Interestingly, not al...

This e-book is available for download at: Leanpub: https://leanpub.com/mechmod_book. The full text here only provides the first 11 pages of the book. The first version was published on 28 August 2021, and several updates have occurred since. ABSTRACT. In this book, I present the basic principles of modelling, and the bare essentials from mathemat...

Survival of early life stages is critical for population growth. Understanding the vulnerability of these sensitive stages can therefore improve ecological risk predictions. The globally-used neonicotinoid insecticide imidaclo-prid does not degrade easily in soil and occurs at concentrations potentially toxic to non-target soil organisms, such as C...

The Dynamic Energy Budget theory (DEB) enables ecotoxicologists to model the effects of chemical stressors on organism life cycles through the coupling of toxicokinetic-toxicodynamic (TK-TD) models. While good progress has been made in the application of DEB-TKTD models for aquatic organisms, applications for soil fauna are scarce, due to the lack...

Toxicokinetic-toxicodynamic (TKTD) models are essential tools to close the gap between laboratory toxicity tests and impacts on individuals under field conditions. For sub-lethal effects on life-history traits, dynamic energy budget (DEB) theory provides a solid basis for TKTD modelling. Various DEB-based TKTD models have been presented, ranging fr...

This e-book is available for download at: Leanpub: https://leanpub.com/debkiss_book. The full text here only provides the first 12 pages of the book. The first version was published on 18 May 2014, and several updates have occurred since. ABSTRACT. Dynamic Energy Budget (DEB) theory is a powerful framework for the energetics of organisms over thei...

The use of cleaner fish is an environmentally-friendly approach to combat the salmon louse, threatening commercial salmon farming. Dynamic Energy Budget (DEB) modelling helps understand the bioenergetics of early life stages of the cleaner fish, and can thereby aid optimisation of their culturing. Here, we report on our attempts to parametrise DEBk...

The assessment of chemical mixture toxicity is one of the major challenges in ecotoxicology. Chemicals can interact, leading to more or less effects than expected, commonly named synergism and antagonism respectively. The classic ad hoc approach for the assessment of mixture effects is based on dose-response curves at a single time point, and is li...

Thanks to growing interest and research in the field, toxicokinetic–toxicodynamic (TKTD) models are close to realising their potential in environmental risk assessment (ERA) of chemicals such as plant protection products. A fundamental application is to find a multiplicative scale factor which—when applied to an exposure profile—results in some spe...

In this study we investigated potential impacts of Cu exposure at low, environmentally relevant, concentrations on early live stages of Atlantic cod (Gadus morhua). Cod embryos and larvae were exposed to 0.5 µg/L (low), 2 µg/L (medium), and 6 µg/L (high) Cu from 4 to 17 days post fertilisation (dpf). Hatching success, mortality, oxygen consumption,...

Understanding growth and development over ontogeny, and the effects of stressors on life history, requires bioenergetic analysis, for example using models based on dynamic energy budget theory. Such analyses require precise and accurate determination of the animal's biomass or biovolume over time. Automated imaging offers great advantages by allowi...

Toxicokinetic‐toxicodynamic (TKTD) modelling is essential to make sense of the time dependence of toxic effects, and to interpret and predict consequences of time‐varying exposure. These advantages have been recognised in the regulatory arena, especially for environmental risk assessment (ERA) of pesticides, where time‐varying exposure is the norm....

Toxicokinetic-toxicodynamic (TKTD) modelling is essential to make sense of the time dependence of toxic effects, and to interpret and predict consequences of time-varying exposure. These advantages have been recognised in the regulatory arena, especially for environmental risk assessment (ERA) of pesticides, where time-varying exposure is the norm....

Marine tailing disposal (MTD) is sometimes practiced as an alternative to traditional mine tailing deposition on land. Environmental challenges connected to MTD include spreading of fine particulate matter in the water column and the potential release of metals and processing chemicals. This study investigated if tailing exposure affects the marine...

Current methods to assess the impact of chemical mixtures on organisms ignore the temporal dimension. The General Unified Threshold model for Survival (GUTS) provides a framework for deriving toxicokinetic–toxicodynamic (TKTD) models, which account for effects of toxicant exposure on survival in time. Starting from the classic assumptions of indepe...

Toxicokinetic‐toxicodynamic (TKTD) models offer a mechanistic understanding of individual‐level toxicity over time, and allow for meaningful extrapolations from laboratory tests to exposure conditions in the field. Thereby, they hold great potential for ecotoxicological studies, both in a regulatory context as well as for basic research. In contras...

Free and open-source software to perform GUTS analysis on toxicity data for survival over time. OpenGUTS is available as a standalone executable as well a Matlab package.

Mechanistic effect models are gaining increasing interest in ecotoxicology and environmental risk assessment (ERA). For explaining effects on an individual's life-history traits (e.g., growth and reproduction), DEBtox is the leading toxicokinetic–toxicodynamic (TKTD) modelling approach. DEBtox is the application of a model based on dynamic energy b...

Hydrogen peroxide (H 2 O 2 ) is used as anti-parasitic veterinary medicine in salmon farms worldwide. In the period from 2009 to 2018 a total of 135 million kg of H 2 O 2 was used in Norway, the world's largest producer of Atlantic salmon. Since the treatment water is discharged to the sea, concerns have been raised about effects of H 2 O 2 on the...

Organism size and growth curves are important biological characteristics. Current methods to measure organism size, and in particular growth curves, are often resource intensive because they involve many manual steps. Here we demonstrate a method for automated, high-throughput measurements of size and growth in individual aquatic invertebrates kept...

Atlantic cod (Gadus morhua) is a commercially important species, and therefore, understanding the influence of environmental factors and anthropogenic stressors on its early life stages is of considerable relevance. In this contribution, we apply a simple and generic energy-budget framework (DEBkiss) to data for the yolk-feeding stages of cod. The...

The risk of accidental oil spills in the Arctic is on the rise due to increased shipping and oil exploration activities, making it essential to calibrate parameters for risk assessment of oil spills to Arctic conditions. The toxicokinetics of crude oil components were assessed by exposing one lipid-poor (CIII) and one lipid-rich (CV) stage of the A...

Environmental risk assessment (ERA) of chemicals relies on the combination of exposure and effects assessment. Exposure concentrations are commonly estimated using mechanistic fate models, but the effects side is restricted to descriptive statistical treatment of toxicity data. Mechanistic effect models are gaining interest in a regulatory context,...

As ecotoxicologists we strive for a better understanding of how chemicals affect our environment. Humanity needs tools to identify those combinations of man-made chemicals and organisms most likely to cause problems. In other words: which of the millions of species are at risk from pollution? And which of the tens of thousands of chemicals contribu...

Efficiently assessing and managing the risks of pollution in the marine environment requires mechanistic models for toxic effects. The General Unified Threshold model for Survival (GUTS) provides a framework for deriving toxicokinetic-toxicodynamic (TKTD) models for the endpoint survival. Two recurring questions in the application of GUTS concern t...

In this investigation, acute toxicity data were used from two previously reported studies where cold-water copepods were exposed to mechanically dispersed (MD) and chemically (CD) dispersed oil. In one of these studies, concentration-dependent mortality was observed, whereas no apparent relationship between exposure concentration and mortality was...

Frameworks for environmental risk assessment (ERA) focus on comparing results from separate exposure and effect assessments. Exposure assessment generally relies on mechanistic fate models, whereas the effects assessment is anchored in standard test protocols and descriptive statistics. This discrepancy prevents a useful link between these two pill...

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms...

Northern krill (Meganyctiphanes norvegica) is an important species in the North Atlantic and the Mediterranean Sea, but very little life-history information is available under controlled (laboratory) conditions. Here, we use the DEBkiss model to piece together the available data into a quantitative energy budget. We use this model to analyse larval...

Models are simplified representations of a part of reality that help us to understand, and ultimately predict, the phenomena that we are interested in. This chapter first provides a general introduction to modeling, focusing on the principles and the concepts rather than on the technicalities. Based on these principles, simple dynamic models are di...

Acute toxicity differs between species, but also varies within a species. Important intra-specific factors are the exposure duration and properties of the animal such as life stage, sex and physiological status. In this study, the acute toxicity of water-soluble fractions (WSFs) from fresh and artificially weathered oil was followed over time in di...

Dynamic Energy Budget (DEB) theory is a generic and comprehensive framework for understanding bioenergetics over the entire life cycle of an organism. Here, we apply a simplified model derived from this theory (DEBkiss) to Antarctic krill Euphausia superba. The model was parameterised using growth curves, and conversion factors for body composition...

Toxicokinetic-toxicodynamic (TKTD) modelling offers many advantages in the analysis of ecotoxicity test data. Calibration of TKTD models, however, places different demands on test design compared to classical concentration-response approaches. In this study we provide useful complementary information regarding test design for TKTD modeling. We pres...

Dynamic models for toxic effects (TKTD models) are increasingly used in the analysis of toxicity data for single-chemical exposure. However, these models also offer a natural extension to the effects of chemical mixtures. Here, we demonstrate how a simple model for the energy budget (DEBkiss) can be used to interpret the effects of cadmium and fluo...

For the ecological risk assessment of toxic chemicals, standardized tests on individuals are often used as proxies for population-level effects. Here, we address the utility of one commonly used metric, reproductive output, as a proxy for population-level effects. Because reproduction integrates the outcome of many interacting processes (e.g., feed...

Individual organisms have to endure transient periods of low‐food supply with consequences for growth, reproduction and survival. To resist starvation, animals usually store resources in their bodies: the larger the animals are, the more resources they can carry, but the more energy they need to allocate for maintaining bodily functions. It is uncl...

In dose-response analysis, regression analysis and hypothesis testing are the main tools of choice. These methods, however, have specific requirements for the design of acute toxicity experiments. To produce meaningful results, both approaches require a constant exposure concentration over the duration of the test, and regression analysis makes an...

The practical usefulness of biomarkers is limited by the complexity of linking their responses to life-history traits of the organisms (e.g., survival, growth, reproduction) over time. Here we present a first attempt to simultaneously model biomarker responses and survival over time with a toxicokinetic-toxicodynamic approach. Even though more work...

Abstract Individual-based models (IBMs) are increasingly used to link the dynamics of individuals to higher levels of biological organization. Still, many IBMs are data hungry, species specific, and time-consuming to develop and analyze. Many of these issues would be resolved by using general theories of individual dynamics as the basis for IBMs. W...

Individual-based models (IBMs) predict how dynamics at higher levels of biological organization emerge from individual-level processes. This makes them a particularly useful tool for ecotoxicology, where the effects of toxicants are measured at the individual level but protection goals are often aimed at the population level or higher. However, one...

The individuals of a species are not equal. These differences frustrate experimental biologists and ecotoxicologists who wish to study the response of a species (in general) to a treatment. In the analysis of data, differences between model predictions and observations on individual animals are usually treated as random 'measurement error' around t...

The term "hormesis" is used to describe dose-response relationships where the response is reversed between low and high doses of a stressor (generally, stimulation at low doses and inhibition at high ones). A mechanistic explanation is needed to interpret the relevance of such responses, but there does not appear to be a single universal mechanism...

Standard ecotoxicological tests are as simple as possible and food sources are mainly chosen for practical reasons. Since some organisms change their food preferences during the life-cycle, they might be food limited at some stage if we do not account for such a switch. As organisms tend to respond more sensitively to toxicant exposure under food l...

Glucosinolates are compounds produced by commercial crops which can hydrolyse in a range of natural toxins that may exert detrimental effects on beneficial soil organisms. This study examined the effects of 2-phenylethyl isothiocyanate and 3-phenylpropionitrile on the survival and growth of the woodlouse Porcellio scaber exposed for 28d. 2-Phenylet...

1. Dynamic Energy Budget (DEB) theory was designed to understand the dynamics of biological systems from cells to populations and ecosystems via a mass balance approach of individuals. However, most work so far has focused on the level of the individual. To encourage further use of DEB theory in a population context, we developed DEB-IBM, a generic...

Models based on Dynamic Energy Budget (DEB) theory offer important advantages in the interpretation of toxicant effects on life-history traits. In contrast to descriptive approaches, they make use of all of the data (all time points, and all endpoints) in one framework, and yield time-independent parameters. In 1996, a suite of simplified DEB model...

We report on the advantages and problems of using toxicokinetic-toxicodynamic (TKTD) models for the analysis, understanding, and simulation of sublethal effects. Only a few toxicodynamic approaches for sublethal effects are available. These differ in their effect mechanism and emphasis on linkages between endpoints. We discuss how the distinction b...

Dynamic Energy Budget (DEB) theory provides a powerful framework for interpreting toxicity data, but is not broadly applied in ecotoxicology yet. One of the reasons is the fact that estimation of DEB parameters from experimental data is certainly not a trivial affair. Almost every data analysis raises new questions, which require the formulation of...

Current measures used to estimate the risks of toxic chemicals are not relevant to the goals of the environmental protection process, and thus ecological risk assessment (ERA) is not used as extensively as it should be as a basis for cost-effective management of environmental resources. Appropriate population models can provide a powerful basis for...

The toxicity of aldicarb on movement, life cycle, population growth rate and resource allocation, and the gene expression changes underpinning these effects, were investigated for Caenorhabditis elegans. A clear effect of aldicarb on nematode movement was found suggesting that this pesticide acts as a neurotoxicant. Aldicarb also had an effect on l...

Toxicokinetic-toxicodynamic models (TKTD models) simulate the time-course of processes leading to toxic effects on organisms. Even for an apparently simple endpoint as survival, a large number of very different TKTD approaches exist. These differ in their underlying hypotheses and assumptions, although often the assumptions are not explicitly state...

The interest of environmental management is in the long-term health of populations and ecosystems. However, toxicity is usually assessed in short-term experiments with individuals. Modelling based on dynamic energy budget (DEB) theory aids the extraction of mechanistic information from the data, which in turn supports educated extrapolation to the...

An organism is a dynamic system, and its life history results from underlying processes in time. The effects of biological and chemical stressors on this system therefore also change temporally. In the present short communication, we emphasize the importance of including time as a factor in stress ecology and ecotoxicology and argue that current st...

Assessment of micro-array sensitivity and signal linearity. Representative analysis of the fluorescent signal generated by 10 RNAs introduced at known concentrations prior to labelling and detected by complementary reporter (8 replicates of each reporter spotted on the array). Panel A are data generated from Cadmium exposure of 40 mg/L array replic...

Assessment of micro-array sensitivity and signal linearity. Representative analysis of the fluorescent signal generated by 10 RNAs introduced at known concentrations prior to labelling and detected by complementary reporter (10 replicates of each reporter spotted on the array). Data were generated from representative arrays selected from transcript...

Assessment of micro-array sensitivity and signal linearity. Representative analysis of the fluorescent signal generated by 10 RNAs introduced at known concentrations prior to labelling and detected by complementary reporter (10 replicates of each reporter spotted on the array). Panel A are data generated from Cadmium control array replicate 4, pane...

Least squares discriminant analysis at reproduction EC50. Scores plot for PC1 and PC2 from PLS-DA of normalised whole genome microarray data for adult C. elegans raised on control NGM media or exposed to (a) Cd, (b) FA, and (c) AZ concentrations approximating to the reproduction EC50 for brood size.

Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to three toxic chemicals: c...

Current approaches to ecological risk assessment (ERA) are not sufficient to address environmental protection goals stated in current regulations in the European Union, North America and elsewhere. For example, the data used to estimate the likelihood of adverse ecological effects typically include responses of survival, growth, or reproduction of...

Studies in ecotoxicology usually focus on a single end point (typically mortality, growth, or reproduction) at a standardized exposure time. The exposure time is chosen irrespective of the properties of the chemical under scrutiny, but should depend on the organism of choice in combination with the compound(s) of interest. This paper discusses the...

In this manuscript we review the use of mechanistic models to interpret effects of mixtures of compounds within the framework of the Dynamic Energy Budget (DEB) theory. Within this approach the effect of a mixture is built up from the effects of the individual components making up the mixture. Understanding effects of mixtures is essential as it is...