Effects of the chorion on the developmental toxicity of organophosphate esters in zebrafish embryos

Tran, Cong M.; Lee, Hyojin; Lee, Byoungcheun; Ra, Jin-Sung; Kim, Ki-Tae

doi:10.1016/j.jhazmat.2020.123389

Cited by 54 publications

(29 citation statements)

References 40 publications

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“…The effect of chorion on developmental toxicity in ZF embryos has previously been investigated following chemical exposure reporting only the effects on phenotypic mortality and morphological traits [21,57]. Recently, researchers found [22] that chorion removal increases embryonic toxicity at the phenotypic level in zebrafish embryos exposed to chemicals adding potential negative effects of dechorination. Taken together, our results suggest that, similar to conclusions by [18] and [58], CompTox ZF assay using embryos survival and overall developmental gross malformations as apical endpoints could help the identification and prioritization of chemicals for more specific, targeted, and MoA-driven testing using ZF embryos as designated model organism.…”

Section: Discussionmentioning

confidence: 99%

“…The use of dechorionated embryos may involve different agreements between sensitivity and specificity [17], due to the higher mortality of embryos. Dechorionation of embryos is desirable as it removes a potential barrier to chemicals, thus allowing a more effective evaluation of toxicity mechanisms that underlie effects of chemical exposure [22].…”

Section: Introductionmentioning

confidence: 99%

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Predictive Capability of QSAR Models Based on the CompTox Zebrafish Embryo Assays: An Imbalanced Classification Problem

et al. 2021

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The CompTox Chemistry Dashboard (ToxCast) contains one of the largest public databases on Zebrafish (Danio rerio) developmental toxicity. The data consists of 19 toxicological endpoints on unique 1018 compounds measured in relatively low concentration ranges. The endpoints are related to developmental effects occurring in dechorionated zebrafish embryos for 120 hours post fertilization and monitored via gross malformations and mortality. We report the predictive capability of 209 quantitative structure–activity relationship (QSAR) models developed by machine learning methods using penalization techniques and diverse model quality metrics to cope with the imbalanced endpoints. All these QSAR models were generated to test how the imbalanced classification (toxic or non-toxic) endpoints could be predicted regardless which of three algorithms is used: logistic regression, multi-layer perceptron, or random forests. Additionally, QSAR toxicity models are developed starting from sets of classical molecular descriptors, structural fingerprints and their combinations. Only 8 out of 209 models passed the 0.20 Matthew’s correlation coefficient value defined a priori as a threshold for acceptable model quality on the test sets. The best models were obtained for endpoints mortality (MORT), ActivityScore and JAW (deformation). The low predictability of the QSAR model developed from the zebrafish embryotoxicity data in the database is mainly due to a higher sensitivity of 19 measurements of endpoints carried out on dechorionated embryos at low concentrations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Predictive Capability of QSAR Models Based on the CompTox Zebrafish Embryo Assays: An Imbalanced Classification Problem

et al. 2021

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“…In zebrafish, the chorion surrounds the embryo for the first 48 hpf [31] and may also serve as a barrier to some chemicals, though its permeability dynamics are not straightforward or well-understood. Recent studies have indicated increased sensitivity to chemicals with the removal of the chorion, including some organophosphate flame retardants and nanomaterials [32][33][34].…”

Section: Effect Of Chorion Status On Bioactivitymentioning

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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“…However, to the best of our knowledge, this is the first study that explored the associations between OPE metabolites and urinary incontinence. For example, an in vitro investigation showed that OPE toxicity led to higher incidence of mortality and malformation in zebrafish embryos (Tran et al 2020;Liu et al 2012). Xu et al reported that tri-ortho-cresyl phosphate (TOCP), a kind of OPE, leads to hepatocellular injury with elevation of serum aminotransferase levels in mice (Xu et al 2016 that triphenyl phosphate (TPP), another kind of OPE, may be associated with an increase in prolactin and decrease in semen quality in men (Meeker and Stapleton 2010).…”

Section: Discussionmentioning

confidence: 99%

The associations between organophosphate esters and urinary incontinence in the general US population

Jin

Qiu

et al. 2021

Environ Sci Pollut Res

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Organophosphate esters (OPEs) impact health in many ways. Since its relationship with urinary incontinence remains unknown, we aimed to explore their associations in the US general population. We combined the results of urine specimens test and self-reported urinary incontinence conditions from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 among 2666 participants and then conducted linear regression and logistic regression to analyse associations between log2-transformed OPE concentrations and urinary incontinence. We found that 0.92% of men and 15.74% of women complained of mixed urinary incontinence (MUI). The concentrations of diphenyl phosphate (DPHP) were significantly correlated to MUI among women when treated as a continuous variable (adjusted odds ratio (OR) = 1.15; 95% confidence interval (CI), 1.01–1.31; p = 0.0369) and as a categorical variable (adjusted OR = 1.24; 95% CI, 1.03–1.49; p for trend = 0.0245), whereas no positive correlation was found in males. There were no significant associations between the other three OPEs: bis(2-chloroethyl) phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and dibutyl phosphate (DBUP). The association of DPHP with an increased prevalence OR of MUI in women is a public health concern; future prospective studies are needed to explore its potential mechanism.

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Effects of the chorion on the developmental toxicity of organophosphate esters in zebrafish embryos

Cited by 54 publications

References 40 publications

Predictive Capability of QSAR Models Based on the CompTox Zebrafish Embryo Assays: An Imbalanced Classification Problem

Predictive Capability of QSAR Models Based on the CompTox Zebrafish Embryo Assays: An Imbalanced Classification Problem

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

The associations between organophosphate esters and urinary incontinence in the general US population

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