A New Statistical Approach to Characterize Chemical-Elicited Behavioral Effects in High-Throughput Studies Using Zebrafish

Zhang, Guozhu; Truong, Lisa; Tanguay, Robert L.; Reif, David M.

doi:10.1371/journal.pone.0169408

Cited by 28 publications

(25 citation statements)

References 15 publications

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“…All statistical estimations were done within ZAAP which uses the R platform ( https://www.r-project.org/ ) for analyses of various morphological and behavioral endpoints; details of analyses are described in our previous publications [ 21 – 23 ]. For mortality and morphology, statistical significance based on binary responses was computed as described in [ 21 , 22 ].…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, significant differences between control and exposed fish were computed using a one-sided Fisher’s exact test, where adverse endpoints were tested to have a greater occurrence in exposed fish. For the photomotor response assay, an entropy score was calculated for each light phase interval and compared with the control group to compute a relative ratio, as described in [ 23 ]. For the startle response assay, the area under the curve (AUC) and peak response was calculated for the first startle only and compared to the first control startle response.…”

Section: Methodsmentioning

confidence: 99%

“…Embryos were collected in water from our recirculating system and sorted according to Kimmel et al 1995 [19]. All exposures and analyses were done based on our well-established high throughput pipeline (described in [20][21][22][23]), with some modifications. At~6 hpf, embryos were bleached and transferred to 6 well flat-bottom plates (Falcon, Corning) with 50 embryos per well and 1 plate (6 wells) per treatment.…”

Section: Exposure Regimementioning

confidence: 99%

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Impacts of high dose 3.5 GHz cellphone radiofrequency on zebrafish embryonic development

et al. 2020

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The rapid deployment of 5G spectrum by the telecommunication industry is intended to promote better connectivity and data integration among various industries. However, since exposures to radio frequency radiations (RFR) >2.4 GHz are still uncommon, concerns about their potential health impacts are ongoing. In this study, we used the embryonic zebrafish model to assess the impacts of a 3.5 GHz RFR on biology-a frequency typically used by 5G-enabled cell phones and lies within the 4G and 5G bandwidth. We established a plate-based exposure setup for RFRs, exposed developing zebrafish to 3.5 GHz RFR, specific absorption rate (SAR) � 8.27 W/Kg from 6 h post fertilization (hpf) to 48 hpf, and measured a battery of morphological and behavioral endpoints at 120 hpf. Our results revealed no significant impacts on mortality, morphology or photomotor response and a modest inhibition of startle response suggesting some levels of sensorimotor disruptions. This suggests that the cell phone radiations at low GHz-level frequencies are likely benign, with subtle sensorimotor effects. Through this assessment, we have established a robust setup for zebrafish RFR exposures readily amenable to testing various powers and frequencies. Future developmental exposure studies in zebrafish will evaluate a wider portion of the radio frequency spectrum to discover the bioactive regions, the potential molecular targets of RFR and the potential long-term effects on adult behavior.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Exposure Regimementioning

confidence: 99%

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Impacts of high dose 3.5 GHz cellphone radiofrequency on zebrafish embryonic development

et al. 2020

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“…The larval photomotor response (LPR) assay was conducted at 120 hpf when the 96-well plates of larvae were placed into ZebraBox behavioral analysis chambers (Viewpoint Life Sciences) and larval movement tracked with ZebraLab motion analysis software for 18 min across 3 cycles of 3 min light: 3 min dark. The distance moved by each larva was integrated over 6 s binning periods, averaged for the test concentration, and area under the curve was calculated and compared to the on-plate control group as previously described [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Systematic Assessment of Exposure Variations on Observed Bioactivity in Zebrafish Chemical Screening

Wilson

Truong

Simonich

et al. 2020

Toxics

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The embryonic zebrafish is a powerful tool for high-throughput screening of chemicals. While this model has significant potential for use in safety assessments and chemical prioritization, a lack of exposure protocol harmonized across laboratories has limited full model adoption. To assess the potential that exposure protocols alter chemical bioactivity, we screened a set of eight chemicals and one 2D nanomaterial across four different regimens: (1) the current Tanguay laboratory’s standard protocol of dechorionated embryos and static exposure in darkness; (2) exposure with chorion intact; (3) exposure under a 14 h light: 10 h dark cycle; and (4) exposure with daily chemical renewal. The latter three regimens altered the concentrations, resulting in bioactivity of the test agents compared to that observed with the Tanguay laboratory’s standard regimen, though not directionally the same for each chemical. The results of this study indicate that with the exception for the 2D nanomaterial, the screening design did not change the conclusion regarding chemical bioactivity, just the nominal concentrations producing the observed activity. Since the goal of tier one chemical screening often is to differentiate active from non-active chemicals, researchers could consider the trade-offs regarding cost, labor, and sensitivity in their study design without altering hit rates. Taken further, these results suggest that it is reasonably feasible to reach agreement on a standardized exposure regiment, which will promote data sharing without sacrificing data content.

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“…Because of the complexity of intact organisms, including early life stages, in vivo assays allow a simultaneous evaluation of (the chemical effect on) many different physiological processes. An example is the use of the fish embryo toxicity assay (Zhang et al ). Although application of mechanistic in vitro bioassays may be more feasible in a monitoring context, they can only detect specific endpoints related to neurotoxicity, immunotoxicity, reproduction, and development, while other effects potentially contributing to such health outcomes may not be detected if nonspecific (in vivo) assays are not included.…”

Section: Selection Of Effect‐based Toolsmentioning

confidence: 99%

Risk‐based approach in the revised European Union drinking water legislation: Opportunities for bioanalytical tools

Dingemans

Baken

Oost³

et al. 2018

Integr Envir Assess & Manag

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A plethora of in vitro bioassays are developed in the context of chemical risk assessment and clinical diagnostics to test effects on different biological processes. Such assays can also be implemented in effect-based monitoring (EBM) of (drinking) water quality alongside chemical analyses. Effects-based monitoring can provide insight into risks for the environment and human health associated with exposure to (unknown) complex, low-level mixtures of micropollutants, which fits in the risk-based approach that was recently introduced in the European Drinking Water Directive. Some challenges remain, in particular those related to selection and interpretation of bioassays. For water quality assessment, carcinogenesis, adverse effects on reproduction and development, effects on xenobiotic metabolism, modulation of hormone systems, DNA reactivity, and adaptive stress responses are considered the most relevant toxicological endpoints. An evaluation procedure of the applicability and performance of in vitro bioassays for water quality monitoring, based on existing information, has been developed, which can be expanded with guidelines for experimental evaluations. In addition, a methodology for the interpretation of in vitro monitoring data is required, because the sensitivity of specific in vitro bioassays in combination with sample concentration may lead to responses of chemicals (far) below exposure concentrations that are relevant for human health effects. Different approaches are proposed to derive effect-based trigger values (EBTs), including EBTs based on (1) relative ecotoxicity potency, (2) health-based threshold values for chronic exposure in humans and kinetics of reference chemicals, and (3) read-across from (drinking) water guideline values. Effects-based trigger values need to be chosen carefully in order to be sufficiently but not overly conservative to indicate potential health effects. Consensus on the crucial steps in the selection and interpretation of in vitro bioassay data will facilitate implementation and legal embedding in the context of water quality monitoring of such assays in EBM strategies. Integr Environ Assess Manag 2018;00:000-000. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

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A New Statistical Approach to Characterize Chemical-Elicited Behavioral Effects in High-Throughput Studies Using Zebrafish

Cited by 28 publications

References 15 publications

Impacts of high dose 3.5 GHz cellphone radiofrequency on zebrafish embryonic development

Impacts of high dose 3.5 GHz cellphone radiofrequency on zebrafish embryonic development

Systematic Assessment of Exposure Variations on Observed Bioactivity in Zebrafish Chemical Screening

Risk‐based approach in the revised European Union drinking water legislation: Opportunities for bioanalytical tools

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