Toxicokinetic and Toxicodynamic Modeling Explains Carry-over Toxicity from Exposure to Diazinon by Slow Organism Recovery

Ashauer, Roman; Hintermeister, Anita; Caravatti, Ivo; Kretschmann, Andreas; Escher, Beate I.

doi:10.1021/es903478b

Cited by 101 publications

(198 citation statements)

References 35 publications

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“…In this case, toxicity is better described as a function of the time of exposure in addition to the dose. Understanding of the mode of action of such compounds is, therefore, essential for a correct prediction of their toxic effects [43]. Thus, whenever the interactions of chemicals with critical receptors are either slowly reversible or irreversible and the resulting biological effects are also irreversible (i.e.…”

Section: Toxicity Assessmentmentioning

confidence: 99%

Environmental Risk Assessment of Agrochemicals — A Critical Appraisal of Current Approaches

Sánchez‐Bayo¹,

Tennekes²

2015

Toxicity and Hazard of Agrochemicals

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This chapter provides insights into the difficulties and challenges of performing risk evaluations of agrochemicals. It is a critical review of the current methodologies used in ecological risk assessment of these chemicals, not their risks to humans. After an introduction to the topic, the current framework for ecological risk assessment is outlined. Two types of assessments are typically carried out depending on the purpose: i) regulatory assessments for registration of a chemical product; and ii) ecological assessments, for the protection of both terrestrial and aquatic ecosystems, which are usually site-specific. Although the general framework is well established, the methodologies used in each of the steps of the assessment are fraught with a number of shortcomings. Notwithstanding the subjectivity implicit in the evaluation of risks, there is scepticism in scientific circles about the appropriateness of the current methodologies because, after so many years of evaluations, we are still incapable of foreseeing the negative consequences that some agrochemicals have in the environment. A critical appraisal of such methodologies is imperative if we are to improve the current assessment process and fix the problems we face today. The chapter reviews first the toxicity assessment methods, pointing to the gaps in knowledge about this essential part of the process and suggesting avenues for further improvement. Deficiencies in the current regulations regarding toxicity testing are discussed, in particular the effect of the time factor on toxicity and the issue of complex mixtures.

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Section: Toxicity Assessmentmentioning

confidence: 99%

Environmental Risk Assessment of Agrochemicals — A Critical Appraisal of Current Approaches

Sánchez‐Bayo¹,

Tennekes²

2015

Toxicity and Hazard of Agrochemicals

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“…Our findings indicate that positive feedback as a function of damage is an important mechanism that can explain patterns of species survival probability exposed varied metal concentrations followed a specific mortality-time profile depicting by the strength of feedback-external stimuli scheme. Our study may provide some insights into the carry-over toxicity concept (Ashauer et al 2010). Generally, carry-over toxicity occurs when organisms exposed to an environmental toxicant survive but carry some damage resulting in reduced fitness (Ashauer et al 2010).…”

Section: Rmse (-)mentioning

confidence: 88%

“…Our study may provide some insights into the carry-over toxicity concept (Ashauer et al 2010). Generally, carry-over toxicity occurs when organisms exposed to an environmental toxicant survive but carry some damage resulting in reduced fitness (Ashauer et al 2010).…”

Section: Rmse (-)mentioning

confidence: 88%

“…Our previous published Astilapia and As-freshwater clam databases meet this principle. Ashauer et al (2007Ashauer et al ( , 2010 modified the DAM to develop a process-based TDM that laid the foundations for predicting survival of aquatic organisms after exposure to sequential pulsed and fluctuating patterns. The primary focus of the present study is on the systems-level viewpoint of the organism damage response.…”

Section: Study Data and Settingsmentioning

confidence: 99%

“…Available experimental evidence (Lee et al 2002a;Ashauer et al 2007Ashauer et al , 2010 indicates that a process-based DAM or referred to as threshold damage model (TDM), is capable of simulating the survival of aquatic organisms exposed to contaminants. It is not inconceivable that this conclusion might be better suited for understanding aquaculture species exposed to toxic metals.…”

Section: Introductionmentioning

confidence: 99%

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Toxicokinetics/toxicodynamics with damage feedback improves risk assessment for tilapia and freshwater clam exposed to arsenic

Chen

Liao

et al. 2011

Ecotoxicology

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It has been proposed that irreversible responses of organisms exposed to contaminants are due to a systems-level feedback. Here we tested this hypothesis by reanalyzing the published data on toxicokinetics and survival probability based on a systems-level threshold damage model (TDM) incorporating with a positive damage feedback to explore the steady-state response and dynamic behavior of damage for tilapia and freshwater clam exposed to waterborne arsenic (As). We found that ultrasensitivity appeared in As-tilapia and freshwater clam systems with Hill coefficient n ≥ 4, indicating that the positive damage feedback mechanism has been triggered. We confirmed that damage can trigger a positive feedback loop that together with As stressor increases irreversibility. This study also showed that TDM with positive feedback gave a much better predictability than that of TDM at As concentrations ranging from 100 to 500 mg l(-1) for freshwater clam, whereas for tilapia, two models had nearly same performance on predictability. We suggested that mortality-time profile derived Hill coefficient could be used as a new risk indicator to assess the survival probability for species exposed to waterborne metals. We anticipated that the proposed toxicokinetics/toxicodynamics with a positive damage feedback may facilitate our understanding and manipulation of complex mechanisms of metal susceptibility among species and improve current risk assessment strategies.

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Toxicokinetic and toxicodynamic model for diazinon toxicity—mechanistic explanation of differences in the sensitivity of Daphnia magna and Gammarus pulex

Kretschmann

Ashauer

Hollender

et al. 2012

Enviro Toxic and Chemistry

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A mechanistic toxicokinetic and toxicodynamic model for acute toxic effects (immobilization, mortality) of the organothiophosphate insecticide diazinon in Daphnia magna is presented. The model was parameterized using measured external and internal (whole-body) concentrations of diazinon, its toxic metabolite diazoxon, and the inactive metabolite 2-isopropyl-6-methyl-4-pyrimidinol, plus acetylcholinesterase (AChE) activity measured during exposure to diazinon in vivo. The toxicokinetic and toxicodynamic model provides a coherent picture from exposure to the resulting toxic effect on an organism level through internally formed metabolites and the effect on a molecular scale. A very fast reaction of diazoxon with AChE (pseudo first-order inhibition rate constant k(i) = 3.3 h(-1)) compared with a slow formation of diazoxon (activation rate constant k(act) = 0.014 h(-1)) was responsible for the high sensitivity of D. magna toward diazinon. Recovery of AChE activity from inhibition was slow and rate-determining (99% recovery within 16 d), compared with a fast elimination of diazinon (99% elimination within 17 h). The obtained model parameters were compared with toxicokinetic and toxicodynamic parameters of Gammarus pulex exposed to diazinon from previous work. This comparison revealed that G. pulex is less sensitive because of a six times faster detoxification of diazinon and diazoxon and an approximately 400 times lower rate for damage accrual. These differences overcompensate the two times faster activation of diazinon to diazoxon in G. pulex compared to D. magna. The present study substantiates theoretical considerations that mechanistically based effect models are helpful to explain sensitivity differences among different aquatic invertebrates.

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Toxicokinetic and Toxicodynamic Modeling Explains Carry-over Toxicity from Exposure to Diazinon by Slow Organism Recovery

Cited by 101 publications

References 35 publications

Environmental Risk Assessment of Agrochemicals — A Critical Appraisal of Current Approaches

Environmental Risk Assessment of Agrochemicals — A Critical Appraisal of Current Approaches

Toxicokinetics/toxicodynamics with damage feedback improves risk assessment for tilapia and freshwater clam exposed to arsenic

Toxicokinetic and toxicodynamic model for diazinon toxicity—mechanistic explanation of differences in the sensitivity of Daphnia magna and Gammarus pulex

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