Generic physiologically-based toxicokinetic modelling for fish: Integration of environmental factors and species variability

Grech, Audrey; Tebby, Cléo; Brochot, Céline; Bois, Frédéric; Bado‐Nilles, Anne; Dorne, Jean‐Lou; Quignot, Nadia; Beaudouin, Rémy

doi:10.1016/j.scitotenv.2018.09.163

Cited by 74 publications

(92 citation statements)

References 125 publications

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“…PBPK models have been published for adult zebrafish, mostly for ecotoxicological risk assessment [18][19][20]. Recently, Brox et al [21] used a one-compartment two-parameter model developed by Gobas and Zhang [22] to explore the impact of physicochemical properties of polar compounds and of biological processes on embryo concentrations.…”

Section: Introductionmentioning

confidence: 99%

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

Siméon

Brotzmann

Fisher

et al. 2020

Reproductive Toxicology

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In order to better explain, predict, or extrapolate to humans the developmental toxicity effects of chemicals to zebrafish (Danio rerio) embryos, we developed a physiologically-based pharmacokinetic (PBPK) model designed to predict organ concentrations of neutral or ionizable chemicals, up to 120 hours post-fertilization. Chemicals' distribution is modeled in the cells, lysosomes, and mitochondria of ten organs of the embryo. The model's partition coefficients are calculated with sub-models using physicochemical properties of the chemicals of interest. The model accounts for organ growth and changes in metabolic clearance with time. We compared ab initio model predictions to data obtained on culture medium and embryo concentrations of valproic acid (VPA) and nine analogs during continuous dosing under the OECD test guideline 236. We further improved the predictions by estimating metabolic clearance and partition coefficients from the data by Bayesian calibration. We also assessed the performance of the model at reproducing data published by Brox et al. (2016) on VPA and 16 other chemicals. We finally compared dose-response relationships calculated for mortality and malformations on the basis of predicted whole embryo concentrations versus those based on nominal water concentrations. The use of target organ concentrations substantially shifted the magnitude of doseresponse parameters and the relative toxicity ranking of chemicals studied.

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Section: Introductionmentioning

confidence: 99%

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

Siméon

Brotzmann

Fisher

et al. 2020

Reproductive Toxicology

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“…These are currently under development at US EPA, JRC, EFSA and under other research programmes and will enable risk assessment based on internal doses of multiple chemicals. Recent examples include generic PB‐K fish models published on EFSA knowledge junction (Grech et al., ,b; Grech et al., ).…”

Section: Way Forward and Recommendationsmentioning

confidence: 99%

Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

More¹,

Bampidis²,

Benford³

et al. 2019

EFS2

270

348

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This Guidance document describes harmonised risk assessment methodologies for combined exposure to multiple chemicals for all relevant areas within EFSA's remit, i.e. human health, animal health and ecological areas. First, a short review of the key terms, scientific basis for combined exposure risk assessment and approaches to assessing (eco)toxicology is given, including existing frameworks for these risk assessments. This background was evaluated, resulting in a harmonised framework for risk assessment of combined exposure to multiple chemicals. The framework is based on the risk assessment steps (problem formulation, exposure assessment, hazard identification and characterisation, and risk characterisation including uncertainty analysis), with tiered and stepwise approaches for both whole mixture approaches and component‐based approaches. Specific considerations are given to component‐based approaches including the grouping of chemicals into common assessment groups, the use of dose addition as a default assumption, approaches to integrate evidence of interactions and the refinement of assessment groups. Case studies are annexed in this guidance document to explore the feasibility and spectrum of applications of the proposed methods and approaches for human and animal health and ecological risk assessment. The Scientific Committee considers that this Guidance is fit for purpose for risk assessments of combined exposure to multiple chemicals and should be applied in all relevant areas of EFSA's work. Future work and research are recommended.

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“…Due to the small size of zebrafish larvae, these studies are challenging given today's technology; however, key advances in bioanalytical techniques supporting zebrafish ADME are being made in the field. [12][13][14] Zebrafish require relatively simple husbandry skills, although regular monitoring for common fish pathogens, whether parasitic or commensalistic, is recommended, as some infections may interfere with study results. 15 Two additional basic traits that have made zebrafish a popular model are that they have high fecundity (a single breeding session typically yields 100-300 fertilized eggs), and the eggs develop externally into free swimming larvae within 5 days post-fertilization (dpf).…”

Section: General Advantages and Challenges Of Zebrafish As An Animal mentioning

confidence: 99%

Zebrafish as an Animal Model for Ocular Toxicity Testing: A Review of Ocular Anatomy and Functional Assays

2020

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Xenobiotics make their way into organisms from diverse sources including diet, medication, and pollution. Our understanding of ocular toxicities from xenobiotics in humans, livestock, and wildlife is growing thanks to laboratory animal models. Anatomy and physiology are conserved among vertebrate eyes, and studies with common mammalian preclinical species (rodent, dog) can predict human ocular toxicity. However, since the eye is susceptible to toxicities that may not involve a histological correlate, and these species rely heavily on smell and hearing to navigate their world, discovering visual deficits can be challenging with traditional animal models. Alternative models capable of identifying functional impacts on vision and requiring minimal amounts of chemical are valuable assets to toxicology. Human and zebrafish eyes are anatomically and functionally similar, and it has been reported that several common human ocular toxicants cause comparable toxicity in zebrafish. Vision develops rapidly in zebrafish; the tiny larvae rely on visual cues as early as 4 days, and behavioral responses to those cues can be monitored in high-throughput fashion. This article describes the comparative anatomy of the zebrafish eye, the notable differences from the mammalian eye, and presents practical applications of this underutilized model for assessment of ocular toxicity.

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Generic physiologically-based toxicokinetic modelling for fish: Integration of environmental factors and species variability

Cited by 74 publications

References 125 publications

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs

Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

Zebrafish as an Animal Model for Ocular Toxicity Testing: A Review of Ocular Anatomy and Functional Assays

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