RESUMO
Molecular, cellular, and organismal alterations are important descriptors of toxic effects, but our ability to extrapolate and predict ecological risks is limited by the availability of studies that link measurable end points to adverse population relevant outcomes such as cohort survival and growth. In this study, we used laboratory gene expression and behavior data from two populations of Atlantic killifish Fundulus heteroclitus [one reference site (SCOKF) and one PCB-contaminated site (NBHKF)] to inform individual-based models simulating cohort growth and survival from embryonic exposures to environmentally relevant concentrations of neurotoxicants. Methylmercury exposed SCOKF exhibited brain gene expression changes in the si:ch211-186j3.6, si:dkey-21c1.4, scamp1, and klhl6 genes, which coincided with changes in feeding and swimming behaviors, but our models simulated no growth or survival effects of exposures. PCB126-exposed SCOKF had lower physical activity levels coinciding with a general upregulation in nucleic and cellular brain gene sets (BGS) and downregulation in signaling, nucleic, and cellular BGS. The NBHKF, known to be tolerant to PCBs, had altered swimming behaviors that coincided with 98% fewer altered BGS. Our models simulated PCB126 decreased growth in SCOKF and survival in SCOKF and NBHKF. Overall, our study provides a unique demonstration linking molecular and behavioral data to develop quantitative, testable predictions of ecological risk.
Assuntos
Fundulidae , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/toxicidade , Fundulidae/genética , Bifenilos Policlorados/toxicidade , Compostos de Metilmercúrio/toxicidade , Comportamento Animal/efeitos dos fármacos , Neurotoxinas/toxicidade , Fundulus heteroclitusRESUMO
Fish swimming behavior is a commonly measured response in aquatic ecotoxicology because behavior is considered a whole organism-level effect that integrates many sensory systems. Recent advancements in animal behavior models, such as hidden Markov chain models (HMM), suggest an improved analytical approach for toxicology. Using both new and traditional approaches, we examined the sublethal effects of PCB126 and methylmercury on yellow perch (YP) larvae (Perca flavescens) using three doses. Both approaches indicate larvae increase activity after exposure to either chemical. The middle methylmercury-dosed larvae showed multiple altered behavior patterns. First, larvae had a general increase in activity, typically performing more behavior states, more time swimming, and more swimming bouts per second. Second, when larvae were in a slow or medium swimming state, these larvae tended to switch between these states more often. Third, larvae swam slower during the swimming bouts. The upper PCB126-dosed larvae exhibited a higher proportion and a fast swimming state, but the total time spent swimming fast decreased. The middle PCB126-dosed larvae transitioned from fast to slow swimming states less often than the control larvae. These results indicate that developmental exposure to very low doses of these neurotoxicants alters YP larvae overall swimming behaviors, suggesting neurodevelopment alteration.
Assuntos
Compostos de Metilmercúrio , Percas , Animais , Larva , Cadeias de Markov , Compostos de Metilmercúrio/toxicidade , Percas/fisiologia , NataçãoRESUMO
BACKGROUND: The sea lamprey (Petromyzon marinus) is a jawless vertebrate that parasitizes fish as an adult and, with overfishing, was responsible for the decline in lake trout (Salvelinus namaycush) populations in the Great Lakes. While laboratory studies have looked at the rates of wounding on various fish hosts, there have been few investigations on the physiological effects of lamprey wounding on the host. In the current study, two morphotypes of lake trout, leans and siscowets, were parasitized in the laboratory by sea lampreys and the liver transcriptomes of parasitized and nonparasitized fish were analyzed by RNA-seq (DESeq2 and edgeR) to determine which genes and gene pathways (Ingenuity Pathway Analysis) were altered by lamprey parasitism. RESULTS: Overall, genes encoding molecules involved in catalytic (e.g., enzymatic) and binding activities (factors and regulators) predominated the regulated gene lists. In siscowets, the top upregulated gene was growth arrest and DNA-damage-inducible protein and for leans it was interleukin-18-binding protein. In leans, the most significantly downregulated gene was UDP-glucuronosyltransferase 2A2 - DESeq2 or phosphotriesterase related - edgeR. For siscowets, the top downregulated gene was C-C motif chemokine 19 - DESeq2 or GTP-binding protein Rhes - edgeR. Gene pathways associated with inflammatory-related responses or factors (cytokines, chemokines, oxidative stress, apoptosis) were regulated following parasitism in both morphotypes. However, pathways related to energy metabolism (glycolysis, gluconeogenesis, lipolysis, lipogenesis) were also regulated. These pathways or the intensity or direction (up/downregulation) of regulation were different between leans and siscowets. Finally, one of the most significantly downregulated pathways in both leans and siscowets was the kynurenine (tryptophan degradation) pathway. CONCLUSIONS: The results indicate a strong transcriptional response in the lake trout to lamprey parasitism that entails genes involved in the regulation of inflammation and cellular damage. Responses to energy utilization as well as hydromineral balance also occurred indicating an adjustment in the host to energy demands and osmotic imbalances during parasitism. Given the role of the kynurenine pathway in promoting immunotolerance in mammals, the downregulation observed in this pathway during parasitism may signify an attempt by the host to inhibit any feedback suppression of the immune response to the lamprey.
Assuntos
Proteínas de Peixes/genética , Perfilação da Expressão Gênica/métodos , Petromyzon/fisiologia , Análise de Sequência de RNA/métodos , Truta/parasitologia , Animais , Metabolismo Energético , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Cinurenina/metabolismo , Lagos , Truta/genéticaRESUMO
Methylmercury (MeHg) is an established neurotoxicant of concern to fish-eating organisms. While most studies have focused on the fish consumers, much less is known about the effects of MeHg on the fish themselves, especially following exposures to chronic and environmentally relevant scenarios. Here we evaluated the behavioral effects of developmental MeHg insult by exposing parental generations of zebrafish to an environmentally realistic MeHg dietary concentration (1 ppm) and two higher concentrations (3 and 10 ppm) throughout their whole life span. Upon reaching adulthood, their offspring were analyzed through a series of behavioral tests, including the visual-motor response (VMR) assay, analysis of spontaneous swimming and evaluation of foraging efficiency. The VMR assay identified decreased locomotor output in the 6 day postfertilization (dpf) offspring of fish exposed to 3 and 10 ppm MeHg. However, in a second test 7 dpf fish revealed an increase in locomotor activity in all MeHg exposures tested. Increases in locomotion continued to be observed until 16 dpf, which coincided with increased foraging efficiency. These results suggest an association between MeHg and hyperactivity, and imply that fish chronically exposed to MeHg in the wild may be vulnerable to predation.
Assuntos
Comportamento Animal/efeitos dos fármacos , Peixe-Zebra , Animais , Dieta , Compostos de Metilmercúrio/farmacologia , NataçãoRESUMO
A 4.1 million m(3) coal ash release into the Emory and Clinch rivers in December 2008 at the Tennessee Valley Authority's Kingston Fossil Plant in east Tennessee, USA, prompted a long-term, large-scale biological monitoring effort to determine if there are chronic effects of this spill on resident biota. Because of the magnitude of the ash spill and the potential for exposure to coal ash-associated contaminants [e.g., selenium (Se), arsenic (As), and mercury (Hg)] which are bioaccumulative and may present human and ecological risks, an integrative, bioindicator approach was used. Three species of fish were monitored-bluegill (Lepomis macrochirus), redear sunfish (L. microlophus), and largemouth bass (Micropterus salmoides)-at ash-affected and reference sites annually for 5 years following the spill. On the same individual fish, contaminant burdens were measured in various tissues, blood chemistry parameters as metrics of fish health, and various condition and reproduction indices. A multivariate statistical approach was then used to evaluate relationships between contaminant bioaccumulation and fish metrics to assess the chronic, sub-lethal effects of exposure to the complex mixture of coal ash-associated contaminants at and around the ash spill site. This study suggests that while fish tissue concentrations of some ash-associated contaminants are elevated at the spill site, there was no consistent evidence of compromised fish health linked with the spill. Further, although relationships between elevated fillet burdens of ash-associated contaminants and some fish metrics were found, these relationships were not indicative of exposure to coal ash or spill sites. The present study adds to the weight of evidence from prior studies suggesting that fish populations have not incurred significant biological effects from spilled ash at this site: findings that are relevant to the current national discussions on the safe disposal of coal ash waste.
Assuntos
Vazamento de Resíduos Químicos , Cinza de Carvão , Monitoramento Ambiental , Reprodução/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Arsênio , Peixes , Mercúrio , Perciformes , Rios/química , Selênio , Tennessee , Poluentes Químicos da Água/análiseRESUMO
Understanding how sublethal impacts of toxicants affect population-relevant outcomes for organisms is challenging. We tested the hypotheses that the well-known sublethal impacts of methylmercury (MeHg) and a polychlorinated biphenyl (PCB126) would have meaningful impacts on cohort growth and survival in yellow perch (Perca flavescens) and Atlantic killifish (Fundulus heteroclitus) populations, that inclusion of model uncertainty is important for understanding the sublethal impacts of toxicants, and that a model organism (zebrafish Danio rerio) is an appropriate substitute for ecologically relevant species (yellow perch, killifish). Our simulations showed that MeHg did not have meaningful impacts on growth or survival in a simulated environment except to increase survival and growth in low mercury exposures in yellow perch and killifish. For PCB126, the high level of exposure resulted in lower survival for killifish only. Uncertainty analyses increased the variability and lowered average survival estimates across all species and toxicants, providing a more conservative estimate of risk. We demonstrate that using a model organism instead of the species of interest does not necessarily give the same results, suggesting that using zebrafish as a surrogate for yellow perch and killifish may not be appropriate for predicting contaminant impacts on larval cohort growth and survival in ecologically relevant species. Our analysis also reinforces the notion that uncertainty analyses are necessary in any modeling assessment of the impacts of toxicants on a population because it provides a more conservative, and arguably realistic, estimate of impact. Environ Toxicol Chem 2024;43:2122-2133. © 2024 SETAC.
Assuntos
Fundulidae , Compostos de Metilmercúrio , Bifenilos Policlorados , Peixe-Zebra , Animais , Peixe-Zebra/crescimento & desenvolvimento , Bifenilos Policlorados/toxicidade , Compostos de Metilmercúrio/toxicidade , Incerteza , Poluentes Químicos da Água/toxicidade , Percas/crescimento & desenvolvimento , Modelos Biológicos , Medição de RiscoRESUMO
Parasitism is an energetically costly event for host species. Dynamic energy budget (DEB) theory describes the metabolic dynamics of an individual organism through its lifetime. Models derived from DEB theory specify how an organism converts food to reserves (maintenance-free energy available for metabolism) and allocates mobilized reserves to maintenance, growth (increase of structural body mass) and maturation or reproduction. DEB models thus provide a useful approach to describe the consequences of parasitism for host species. We developed a DEB model for siscowet lake trout and modeled the impact of sea lamprey parasitism on growth and reproduction using data collected from studies documenting the long-term effects following a non-lethal sea lamprey attack. The model was parameterized to reflect the changes in allocation of energy towards growth and reproduction observed in lake trout following sea lamprey parasitism and includes an estradiol module that describes the conversion of reproductive reserves to ovarian mass based on estradiol concentration. In our DEB model, parasitism increased somatic and maturity maintenance costs, reduced estradiol and decreased the estradiol-mediated conversion efficiency of reproductive reserves to ovarian mass. Muscle lipid composition of lake trout influenced energy mobilization from the reserve (efficiency of converting reserves allocated to reproduction into eggs) and reproductive efficiency. These model changes accurately reflect observed empirical changes to ovarian mass and growth. This model provides a plausible explanation of the energetic mechanisms that lead to skipped spawning following sea lamprey parasitism and could be used in population models to explore sublethal impacts of sea lamprey parasitism and other stressors on population dynamics.
RESUMO
The energetic demands of stressors like parasitism require hosts to reallocate energy away from normal physiological processes to survive. Life history theory provides predictions about how hosts will reallocate energy following parasitism, but few studies provide empirical evidence to test these predictions. We examined the sub-lethal effects of sea lamprey parasitism on lean and siscowet lake charr, two ecomorphs with different life history strategies. Leans are shorter lived, faster growing, and reach reproductive maturity earlier than siscowets. Following a parasitism event of 4 days, we assessed changes to energy allocation by monitoring endpoints related to reproduction, energy storage, and growth. Results indicate that lean and siscowet lake charr differ considerably in their response to parasitism. Severely parasitized leans slightly increased their reproductive effort and maintained growth and energy storage, consistent with expectations based on life history that leans are less likely to survive parasitism and have shorter lifespans than siscowets making investing in immediate reproduction more adaptive. Siscowets nearly ceased reproduction following severe parasitism and showed evidence of altered energy storage, consistent with a strategy that favors maximizing long-term reproductive success. These findings suggest that life history can be used to generalize stressor response between populations and can aid management efforts.
Assuntos
Petromyzon , Truta , Animais , Lagos , Reprodução/fisiologia , SimbioseRESUMO
Many biological systems across scales of size and complexity exhibit a time-varying complex network structure that emerges and self-organizes as a result of interactions with the environment. Network interactions optimize some intrinsic cost functions that are unknown and involve for example energy efficiency, robustness, resilience, and frailty. A wide range of networks exist in biology, from gene regulatory networks important for organismal development, protein interaction networks that govern physiology and metabolism, and neural networks that store and convey information to networks of microbes that form microbiomes within hosts, animal contact networks that underlie social systems, and networks of populations on the landscape connected by migration. Increasing availability of extensive (big) data is amplifying our ability to quantify biological networks. Similarly, theoretical methods that describe network structure and dynamics are being developed. Beyond static networks representing snapshots of biological systems, collections of longitudinal data series can help either at defining and characterizing network dynamics over time or analyzing the dynamics constrained to networked architectures. Moreover, due to interactions with the environment and other biological systems, a biological network may not be fully observable. Also, subnetworks may emerge and disappear as a result of the need for the biological system to cope with for example invaders or new information flows. The confluence of these developments renders tractable the question of how the structure of biological networks predicts and controls network dynamics. In particular, there may be structural features that result in homeostatic networks with specific higher-order statistics (e.g., multifractal spectrum), which maintain stability over time through robustness and/or resilience to perturbation. Alternative, plastic networks may respond to perturbation by (adaptive to catastrophic) shifts in structure. Here, we explore the opportunity for discovering universal laws connecting the structure of biological networks with their function, positioning them on the spectrum of time-evolving network structure, that is, dynamics of networks, from highly stable to exquisitely sensitive to perturbation. If such general laws exist, they could transform our ability to predict the response of biological systems to perturbations-an increasingly urgent priority in the face of anthropogenic changes to the environment that affect life across the gamut of organizational scales.
Assuntos
Algoritmos , Animais , HomeostaseRESUMO
Problem formulation (PF) is a critical initial step in planning risk assessments for chemical exposures to wildlife, used either explicitly or implicitly in various jurisdictions to include registration of new pesticides, evaluation of new and existing chemicals released to the environment, and characterization of impact when chemical releases have occurred. Despite improvements in our understanding of the environment, ecology, and biological sciences, few risk assessments have used this information to enhance their value and predictive capabilities. In addition to advances in organism-level mechanisms and methods, there have been substantive developments that focus on population- and systems-level processes. Although most of the advances have been recognized as being state-of-the-science for two decades or more, there is scant evidence that they have been incorporated into wildlife risk assessment or risk assessment in general. In this article, we identify opportunities to consider elevating the relevance of wildlife risk assessments by focusing on elements of the PF stage of risk assessment, especially in the construction of conceptual models and selection of assessment endpoints that target population- and system-level endpoints. Doing so will remain consistent with four established steps of existing guidance: (1) establish clear protection goals early in the process; (2) consider how data collection using new methods will affect decisions, given all possibilities, and develop a decision plan a priori; (3) engage all relevant stakeholders in creating a robust, holistic conceptual model that incorporates plausible stressors that could affect the targets defined in the protection goals; and (4) embrace the need for iteration throughout the PF steps (recognizing that multiple passes may be required before agreeing on a feasible plan for the rest of the risk assessment). Integr Environ Assess Manag 2022;00:1-16. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
RESUMO
We used a field experiment, population modeling, and an analysis of 30 years of data from walleye (Sander vitreus; a freshwater fish) in Lake Erie to show that maternal influences on offspring survival can affect population dynamics. We first demonstrate experimentally that the survival of juvenile walleye increases with egg size (and, to a lesser degree, female energy reserves). Because egg size in this species tends to increase with maternal age, we then model these maternal influences on offspring survival as a function of maternal age to show that adult age structure can affect the maximum rate at which a population can produce new adults. Consistent with this hypothesis, we present empirical evidence that the maximum reproductive rate of an exploited population of walleye was approximately twice as high when older females were abundant as compared to when they were relatively scarce. Taken together, these results indicate that age- or size-based maternal influences on offspring survival can be an important mechanism driving population dynamics and that exploited populations could benefit from management strategies that protect, rather than target, reproductively valuable individuals.
Assuntos
Água Doce , Perciformes/fisiologia , Animais , Conservação dos Recursos Naturais , Ecossistema , Feminino , Masculino , Modelos Biológicos , Dinâmica Populacional , Reprodução , Razão de MasculinidadeRESUMO
Coal ash contains numerous contaminants and is the focus of regulatory actions and risk assessments due to environmental spills. We exposed Daphnia magna to a gradient of coal ash contamination under high and low food rations to assess the sublethal effects of dietary exposures. Whereas exposure to contaminants resulted in significant reductions in growth and reproduction in daphnids, low, environmentally relevant food rations had a much greater effect on these endpoints. Environ Toxicol Chem 2020;39:1998-2007. © 2020 SETAC.
Assuntos
Cinza de Carvão/toxicidade , Daphnia/efeitos dos fármacos , Exposição Dietética/efeitos adversos , Poluentes Químicos da Água/toxicidade , Animais , Bioacumulação/efeitos dos fármacos , Cinza de Carvão/metabolismo , Daphnia/crescimento & desenvolvimento , Exposição Dietética/análise , Modelos Teóricos , Reprodução/efeitos dos fármacos , Poluentes Químicos da Água/metabolismoRESUMO
Knowledge of the relationship between the number of offspring produced (recruitment) and adult abundance is fundamental to forecasting the dynamics of an exploited population. Although small-scale experiments have documented the importance of maternal quality to offspring survival in plants and animals, the effects of this association on the recruitment dynamics of exploited populations are largely unknown. Here, we present results from both a simple population model and a meta-analysis of time-series data from 25 species of exploited marine fishes that suggest that a population of older, larger individuals has a higher maximum reproductive rate than an equivalent population of younger, smaller individuals, and that this difference increases with the reproductive lifespan of the population. These findings (i) establish an empirical link between population age structure and reproductive rate that is consistent with strong effects of maternal quality on population dynamics and (ii) provide further evidence that extended age structure is essential to the sustainability of many exploited fish stocks.
Assuntos
Peixes/fisiologia , Reprodução/fisiologia , Animais , Conservação dos Recursos Naturais , Feminino , Pesqueiros , Modelos Biológicos , Oceanos e Mares , Dinâmica PopulacionalRESUMO
Prairie hay meadows are important reservoirs of grassland biodiversity in the tallgrass prairie regions of the central United States and are the object of increasing attention for conservation and restoration. In addition, there is growing interest in the potential use of such low-input, high-diversity (LIHD) native grasslands for biofuel production. The uplands of eastern Kansas, USA, which prior to European settlement were dominated by tallgrass prairie, are currently utilized for intensive agriculture or exist in a state of abandonment from agriculture. The dominant grasslands in the region are currently high-input, low-diversity (HILD) hay fields seeded to introduced C3 hay grasses. We present results from a long-term experiment conducted in a recently abandoned HILD hay field in eastern Kansas to evaluate effects of fertilization, haying, and native species sowing on community dynamics, biomass, and potential for restoration to native LIHD hay meadow. Fertilized plots maintained dominance by introduced grasses, maintained low diversity, and were largely resistant to colonization throughout the study. Non-fertilized plots exhibited rapid successional turnover, increased diversity, and increased abundance of C4 grasses over time. Haying led to modest changes in species composition and lessened the negative impact of fertilization on diversity. In non-fertilized plots, sowing increased representation by native species and increased diversity, successional turnover, and biomass production. Our results support the shifting limitations hypothesis of community organization and highlight the importance of species pools and seed limitations in constraining successional turnover, community structure, and ecosystem productivity under conditions of low fertility. Our findings also indicate that several biological and functional aspects of LIHD hay meadows can be restored from abandoned HILD hay fields by ceasing fertilization and reintroducing native species through sowing. Declines in primary production and hay yield that result from the cessation of fertilization may be at least partially compensated for by restoration.
Assuntos
Agricultura , Conservação dos Recursos Naturais/métodos , Biomassa , Ecossistema , Monitoramento Ambiental , Kansas , Modelos Biológicos , Fenômenos Fisiológicos Vegetais , Dinâmica Populacional , Fatores de TempoRESUMO
Recently, hypoxia has been shown to act as an endocrine disruptor. We used a model of vitellogenesis in a female sciaenid fish to simulate the effects of hypoxia and to determine if reproductive impairment observed in field-caught fish could be attributed to dissolved oxygen conditions at the sampling sites. The model is a set of coupled, ordinary differential equations that simulate major biochemical reactions from the secretion of gonadotropin to production of vitellogenin. Various intermediate variables in the model correspond to commonly measured biomarkers, and we assume a direct relationship between cumulative vitellogenin (VTG) and the gonadosomatic index (GSI). Model predictions were compared to results of laboratory studies that examined the effects of hypoxia on Atlantic croaker (Micropogonias undulatus) reproduction. When hypoxia was assumed to cause reduced gonadotropin and impaired aromatase activity, model predictions of VTG production were similar to laboratory-measured reductions in GSI. The model was then applied to reproductive biomarkers measured in fish from normoxic and hypoxic locations in Pensacola Bay (FL, U.S.A.). We simulated the relationship between reduced estradiol-17beta and VTG production under hypoxia, and we compared these results with field data. Good agreement between field and simulation results suggested that croaker collected from hypoxic sites in October were exposed to hypoxic conditions for an extended period during gonadal recrudescence and that hypoxia was a dominant cause for the reduced GSIs. Monte Carlo uncertainty analyses suggested that the maximum rate of free testosterone production is the most sensitive parameter. Our simulations demonstrated that the model can be used identifying the mechanism underlying endocrine disruption and for interpreting field-measured biomarkers in situations of multiple stressors.
Assuntos
Biomarcadores/análise , Glândulas Endócrinas/efeitos dos fármacos , Hipóxia , Modelos Biológicos , Vitelogeninas/biossíntese , Animais , Disruptores Endócrinos/toxicidade , Glândulas Endócrinas/metabolismo , Feminino , Perciformes , IncertezaRESUMO
In 2007 the United States National Research Council (NRC) published a vision for toxicity testing in the 21st century that emphasized the use of in vitro high-throughput screening (HTS) methods and predictive models as an alternative to in vivo animal testing. In the present study we examine the state of the science of HTS and the progress that has been made in implementing and expanding on the NRC vision, as well as challenges to implementation that remain. Overall, significant progress has been made with regard to the availability of HTS data, aggregation of chemical property and toxicity information into online databases, and the development of various models and frameworks to support extrapolation of HTS data. However, HTS data and associated predictive models have not yet been widely applied in risk assessment. Major barriers include the disconnect between the endpoints measured in HTS assays and the assessment endpoints considered in risk assessments as well as the rapid pace at which new tools and models are evolving in contrast with the slow pace at which regulatory structures change. Nonetheless, there are opportunities for environmental scientists and policymakers alike to take an impactful role in the ongoing development and implementation of the NRC vision. Six specific areas for scientific coordination and/or policy engagement are identified. Environ Toxicol Chem 2019;38:12-26. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Assuntos
Ensaios de Triagem em Larga Escala/métodos , Medição de Risco , Animais , Poluentes Ambientais/análise , Humanos , Modelos Teóricos , Testes de ToxicidadeRESUMO
An important goal in toxicology is the development of new ways to increase the speed, accuracy, and applicability of chemical hazard and risk assessment approaches. A promising route is the integration of in vitro assays with biological pathway information. We examined how the adverse outcome pathway (AOP) framework can be used to develop pathway-based quantitative models useful for regulatory chemical safety assessment. By using AOPs as initial conceptual models and the AOP knowledge base as a source of data on key event relationships, different methods can be applied to develop computational quantitative AOP models (qAOPs) relevant for decision making. A qAOP model may not necessarily have the same structure as the AOP it is based on. Useful AOP modeling methods range from statistical, Bayesian networks, regression, and ordinary differential equations to individual-based models and should be chosen according to the questions being asked and the data available. We discuss the need for toxicokinetic models to provide linkages between exposure and qAOPs, to extrapolate from in vitro to in vivo, and to extrapolate across species. Finally, we identify best practices for modeling and model building and the necessity for transparent and comprehensive documentation to gain confidence in the use of qAOP models and ultimately their use in regulatory applications. Environ Toxicol Chem 2019;38:1850-1865. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Assuntos
Ecotoxicologia/métodos , Substâncias Perigosas/toxicidade , Modelos Teóricos , Rotas de Resultados Adversos , Animais , Teorema de Bayes , Tomada de Decisões , Substâncias Perigosas/farmacocinética , Humanos , Projetos de Pesquisa , Medição de Risco , ToxicocinéticaRESUMO
1. The simple bioenergetic models in the family of Dynamic Energy Budget (DEB) consist of a small number of state equations quantifying universal processes, such as feeding, maintenance, development, reproduction and growth. Linking these organismal level processes to underlying suborganismal mechanisms at the molecular, cellular and organ level constitutes a major challenge for predictive ecological risk assessments. 2. Motivated by the need for process-based models to evaluate the impact of endocrine disruptors on ecologically relevant endpoints, this paper develops and evaluates two general modeling modules describing demand-driven feedback mechanisms exerted by gonads on the allocation of resources to production of reproductive matter within the DEB modeling framework. 3. These modules describe iteroparous, semelparous and batch-mode reproductive strategies. The modules have a generic form with both positive and negative feedback components; species and sex specific attributes of endocrine regulation can be added without changing the core of the modules. 4. We demonstrate that these modules successfully describe time-resolved measurements of wet weight of body, ovaries and liver, egg diameter and plasma content of vitellogenin and estradiol in rainbow trout (Oncorynchus mykiss) by fitting these models to published and new data, which require the estimation of less than two parameters per data type. 5. We illustrate the general applicability of the concept of demand-driven allocation of resources to reproduction as worked out in this paper by evaluating one of the modules with data on growth and seed production of an annual plant, the common bean (Phaseolis vulgaris).
RESUMO
Expressing the sublethal effects of contaminants measured on individual fish as cohort and population responses would greatly help in their interpretation. Our approach combines laboratory studies with coupled statistical and individual-based models to simulate the effects of methylmercury (MeHg) on Atlantic croaker larval survival and growth. We used results of video-taped laboratory experiments on the effects of MeHg on larval behavioral responses to artificial predatory stimuli. Laboratory results were analyzed with a regression tree to obtain the probability of control and MeHg-exposed larvae escaping a real predatory fish attack. Measured changes in swimming speeds and regression tree-predicted escape abilities induced by MeHg exposure were then inputted into an individual-based larval fish cohort model. The individual-based model predicted larval-stage growth and survival under baseline (control) conditions, and low- and high-dose MeHg exposure under two alternative predator composition scenarios (medusa-dominated and predatory fish-dominated). Under MeHg exposure, stage survival was 7-19% of baseline (control) survival, and the roughly 33-day stage duration was extended by about 1-4 days. MeHg effects on larval growth dominated the response under the medusa-dominated predator composition, while predation played a more important role under the fish-dominated predator composition. Simulation results suggest that MeHg exposures near extreme maximum values observed in field studies can have a significant impact on larval cohort dynamics, and that the characteristics of the predator-prey interactions can greatly influence the underlying causes of the predicted responses.
Assuntos
Comportamento Animal/efeitos dos fármacos , Compostos de Metilmercúrio/toxicidade , Modelos Biológicos , Perciformes/crescimento & desenvolvimento , Poluentes Químicos da Água/toxicidade , Animais , Tamanho Corporal , Simulação por Computador , Reação de Fuga/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Análise de Sobrevida , Natação , Fatores de Tempo , Zooplâncton/fisiologiaRESUMO
A working group at the National Institute for Mathematical and Biological Synthesis (NIMBioS) explored the feasibility of integrating 2 complementary approaches relevant to ecological risk assessment. Adverse outcome pathway (AOP) models provide "bottom-up" mechanisms to predict specific toxicological effects that could affect an individual's ability to grow, reproduce, and/or survive from a molecular initiating event. Dynamic energy budget (DEB) models offer a "top-down" approach that reverse engineers stressor effects on growth, reproduction, and/or survival into modular characterizations related to the acquisition and processing of energy resources. Thus, AOP models quantify linkages between measurable molecular, cellular, or organ-level events, but they do not offer an explicit route to integratively characterize stressor effects at higher levels of organization. While DEB models provide the inherent basis to link effects on individuals to those at the population and ecosystem levels, their use of abstract variables obscures mechanistic connections to suborganismal biology. To take advantage of both approaches, we developed a conceptual model to link DEB and AOP models by interpreting AOP key events as measures of damage-inducing processes affecting DEB variables and rates. We report on the type and structure of data that are generated for AOP models that may also be useful for DEB models. We also report on case studies under development that merge information collected for AOPs with DEB models and highlight some of the challenges. Finally, we discuss how the linkage of these 2 approaches can improve ecological risk assessment, with possibilities for progress in predicting population responses to toxicant exposures within realistic environments. Integr Environ Assess Manag 2018;14:615-624. © 2018 SETAC.