Assessing the ecotoxicity of potentially neurotoxic substances – Evaluation of a behavioural parameter in the embryogenesis of Danio rerio

Weichert, Fabian G.; Floeter, Carolin; Artmann, Adriana S. Meza; Kammann, Ulrike

doi:10.1016/j.chemosphere.2017.07.136

Cited by 35 publications

(24 citation statements)

References 35 publications

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“…These substances included glyphosate,23242526 chlorpyrifos,927 diazinon,282930 acephate,313233 malathion,333435 permethrin,69 bifenthrin,93336 methyl bromide,3738 imidacloprid,3940 avermectin,4142 and myclobutanil 1443…”

Section: Methodsmentioning

confidence: 99%

Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study

Ehrenstein

Ling

Cui

et al. 2019

BMJ

208

165

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Objective To examine associations between early developmental exposure to ambient pesticides and autism spectrum disorder. Design Population based case-control study. Setting California’s main agricultural region, Central Valley, using 1998-2010 birth data from the Office of Vital Statistics. Population 2961 individuals with a diagnosis of autism spectrum disorder based on the Diagnostic and Statistical Manual of Mental Disorders , fourth edition, revised (up to 31 December 2013), including 445 with intellectual disability comorbidity, were identified through records maintained at the California Department of Developmental Services and linked to their birth records. Controls derived from birth records were matched to cases 10:1 by sex and birth year. Exposure Data from California state mandated Pesticide Use Reporting were integrated into a geographic information system tool to estimate prenatal and infant exposures to pesticides (measured as pounds of pesticides applied per acre/month within 2000 m from the maternal residence). 11 high use pesticides were selected for examination a priori according to previous evidence of neurodevelopmental toxicity in vivo or in vitro (exposure defined as ever v never for each pesticide during specific developmental periods). Main outcome measure Odds ratios and 95% confidence intervals using multivariable logistic regression were used to assess associations between pesticide exposure and autism spectrum disorder (with or without intellectual disabilities) in offspring, adjusting for confounders. Results Risk of autism spectrum disorder was associated with prenatal exposure to glyphosate (odds ratio 1.16, 95% confidence interval 1.06 to 1.27), chlorpyrifos (1.13, 1.05 to 1.23), diazinon (1.11, 1.01 to 1.21), malathion (1.11, 1.01 to 1.22), avermectin (1.12, 1.04 to 1.22), and permethrin (1.10, 1.01 to 1.20). For autism spectrum disorder with intellectual disability, estimated odds ratios were higher (by about 30%) for prenatal exposure to glyphosate (1.33, 1.05 to 1.69), chlorpyrifos (1.27, 1.04 to 1.56), diazinon (1.41, 1.15 to 1.73), permethrin (1.46, 1.20 to 1.78), methyl bromide (1.33, 1.07 to 1.64), and myclobutanil (1.32, 1.09 to 1.60); exposure in the first year of life increased the odds for the disorder with comorbid intellectual disability by up to 50% for some pesticide substances. Conclusion Findings suggest that an offspring’s risk of autism spectrum disorder increases following prenatal exposure to ambient pesticides within 2000 m of their mother’s residence during pregnancy, compared with offspring of women from the same agricultural region without such exposure. Infant exposure could further increase risks for autism spectrum disorder with comorbid intellectual disability.

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Section: Methodsmentioning

confidence: 99%

Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study

Ehrenstein

Ling

Cui

et al. 2019

BMJ

208

165

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“…However, not only the oxon-metabolite but also the parent compound of chlorpyrifos induced hyperactivity in the STC at an earlier developmental stage of 24 hpf (with potential limited biotransformation). This suggests the influential AChE inhibiting activity of chlorpyrifos or a high efficacy of the low amount of the oxon-metabolite resulting from the limited biotransformation [120,121]. Reif et al [89] also found a relatively lower effect concentration (0.64 µM) for chlorpyrifos-oxon compared to chlorpyrifos (64 µM) and this supports the limited biotransformation of chlorpyrifos in younger developmental stages.…”

Section: Organophosphatesmentioning

confidence: 94%

“…Beside the test container material, the ratio of surface area to volume could also induce variability. The reported effect concentration for emamectin is over 40 times lower when embryos were exposed in 24-well plates [121] compared to exposure in 384-well plates [86]. This could be the result of higher well absorption area with respect to volume in 384-well plates leading to higher adsorption.…”

Section: Materials Used For Exposure Vesselsmentioning

confidence: 96%

“…First, abamectin comparison in which the STC studies [87,121] showed similar effect concentrations to another PMR study [89]. Second, behavioral effects were observed for carbamazepine in the STC test [121] at a concentration not tested in the PMR [89]. The chemicals that show inconsistencies include; fipronil, chlorpyrifos and emamectin.…”

Section: Comparison Of Stc and Pmr Case Study: Fipronil Emamectin Bementioning

confidence: 96%

“…This event is assumed to be important for the hatching of the embryo from its chorion but evidence for a role of STC for hatching has not yet been provided [58,98]. Frequency changes of the STC have been used as a tool to detect the effects of neuroactive chemicals in developing embryo [118,121].…”

Section: Types Of Behavioral Tests Considered In This Reviewmentioning

confidence: 99%

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Hypo- or hyperactivity of zebrafish embryos provoked by neuroactive substances: a review on how experimental parameters impact the predictability of behavior changes

et al. 2019

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Tests with zebrafish embryos have gained wide acceptance as an alternative test model for drug development and toxicity testing. In particular, the behavioral response of the zebrafish embryo is currently seen as a useful endpoint to diagnose neuroactive substances. Consequently, several behavioral test methods have been developed addressing various behavioral endpoints such as spontaneous tail coiling (STC), photomotor response (PMR), locomotor response (LMR) and alternating light/dark-induced locomotor response (LMR-L/D). Although these methods are distinct in their application, most of their protocols differ quite strongly in the use of experimental parameters and this is usually driven by different research questions. However, if a single mode of action is to be diagnosed, then varying experimental parameters may cause incoherent behavioral responses (hypo-or hyperactivity) of zebrafish during toxicity assessment. This could lead to inconclusiveness of behavioral test results for use within a prospective and diagnostic risk assessment framework. To investigate the influence of these parameters, we conducted a review of existing behavioral assays to address the following two questions: (1) To what extent do varying experimental parameters influence observed effects in published behavioral test methods? (2) Is the observed behavior change (hypo-or hyperactivity) of zebrafish embryos consistent with the expected mode of action of a chemical? We compiled a set of 18 substances which are anticipated to be neuroactive. We found that behavioral changes are not only affected by chemicals but also variation in the use of experimental parameters across studies seems to have a high impact on the outcome and thus comparability between studies. Four parameters, i.e., exposure concentration, exposure duration, endpoint parameter and developmental stage were the most influential parameters. Varying combinations of these parameters caused a non-reproducible outcome for the hyperactivity expected for the organophosphates; chlorpyrifos and diazinon. We highlighted that the STC test shows a higher capacity to predict the hyperactivity of organophosphates, while PMR and LMR-L/D were more suitable to predict the hypoactivity expected for anticonvulsants. We provide a list of recommendations which, when implemented, may help to exclude the risk of bias due to experimental parameters if similar goals are desired.

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Approaches to Test the Neurotoxicity of Environmental Contaminants in the Zebrafish Model: From Behavior to Molecular Mechanisms

Fitzgerald

Könemann

Krümpelmann

et al. 2021

Enviro Toxic and Chemistry

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The occurrence of neuroactive chemicals in the aquatic environment is on the rise and poses a potential threat to aquatic biota of currently unpredictable outcome. In particular, subtle changes caused by these chemicals to an organism's sensation or behavior are difficult to tackle with current test systems that focus on rodents or with in vitro test systems that omit whole-animal responses. In recent years, the zebrafish (Danio rerio) has become a popular model organism for toxicological studies and testing strategies, such as the standardized use of zebrafish early life stages in the Organisation for Economic Cooperation and Development's guideline 236. In terms of neurotoxicity, the zebrafish provides a powerful model to investigate changes to the nervous system from several different angles, offering the ability to tackle the mechanisms of action of chemicals in detail. The mechanistic understanding gained through the analysis of this model species provides a good basic knowledge of how neuroactive chemicals might interact with a teleost nervous system. Such information can help infer potential effects occurring to other species exposed to neuroactive chemicals in their aquatic environment and predicting potential risks of a chemical for the aquatic ecosystem. In the present article, we highlight approaches ranging from behavioral to structural, functional, and molecular analysis of the larval zebrafish nervous system, providing a holistic view of potential neurotoxic outcomes.

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Assessing the ecotoxicity of potentially neurotoxic substances – Evaluation of a behavioural parameter in the embryogenesis of Danio rerio

Cited by 35 publications

References 35 publications

Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study

Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study

Hypo- or hyperactivity of zebrafish embryos provoked by neuroactive substances: a review on how experimental parameters impact the predictability of behavior changes

Approaches to Test the Neurotoxicity of Environmental Contaminants in the Zebrafish Model: From Behavior to Molecular Mechanisms

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