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Toxics
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Fish Models for Human Toxicology
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Fish Models for Human Toxicology

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Novel Methods in Toxicology Research".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 32885

Special Issue Editors

Dr. Demetrio Raldúa

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Guest Editor
Department Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona, Spain
Interests: fish neurotoxicology; zebrafish model; fish developmental neurotoxicology
Special Issues, Collections and Topics in MDPI journals
Dr. Benjamin Piña

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Guest Editor
Institute of Environmental Assessment and Water Research, IDAEA-CSIC, Barcelona, Catalunya 08034, Spain
Interests: ecotoxicology; molecular biology; biochemistry; omics
Dr. Natalia Garcia-Reyero

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Guest Editor
Institute for Genomics, Biocomputing & Biotechnology, Mississippi State University, Starkville, MS 39759, USA
Interests: toxicogenomics; predictive toxicology; zebrafish; adverse outcome pathways
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Whereas many of the human toxidromes have already been modelized in rodents, only a few models have been developed and conveniently validated in fish. Before proposing the use of any fish model of human toxidromes, the validity of the developed model should always be tested. Thus, an intensive effort should be made to characterize the effects of the toxicant at different levels of biological organization, from molecular to behavioral, in the developed model as a part of the validation process. As fish are considered a less-sentient organism, even adult fish models of human toxidromes fully meet the 3Rs principles. This advantage makes fish ideal for the initial screening and prioritization of chemicals providing protection against the toxidromes, as only the most promising drugs would be further validated in a rodent model. This approach makes it possible to obtain highly predictive results for humans, because if one drug provides protection against a neurotoxic in both fish and rodents (two phylogenetically distant vertebrate models), it is likely working through highly conserved mechanisms, and there is thus a high probability that it will also be useful in protecting humans against the same toxidrome.

This Special Issue on “Fish Models for Human Toxicology” aims to highlight the research into the development and validation of human toxidromes using well-established fish models in biomedicine, such as zebrafish or medaka. We are also interested in studies using fish models to increase our current mechanistic understanding of human toxidromes, identifying new potential therapeutic targets and developing more effective therapies.

Authors are invited and welcome to submit original research papers, reviews, and short communications.

Dr. Demetrio Raldúa
Dr. Benjamin Piña
Dr. Natalia Garcia-Reyero
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • fish models
  • toxicology
  • adverse outcome pathways
  • treatment
  • validity process
  • mechanistic approach

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Published Papers (10 papers)

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Research

15 pages, 3275 KiB  
Article
Embryonic Nicotine Exposure Disrupts Adult Social Behavior and Craniofacial Development in Zebrafish
by Gissela Borrego-Soto and Johann K. Eberhart
Toxics 2022, 10(10), 612; https://doi.org/10.3390/toxics10100612 - 15 Oct 2022
Cited by 11 | Viewed by 2743
Abstract
Cigarette smoking remains the leading cause of preventable death and morbidity worldwide. Smoking during pregnancy is associated with numerous adverse birth outcomes, including craniofacial and behavioral abnormalities. Although tobacco smoke contains more than 4000 toxic substances, nicotine is addictive and is likely the [...] Read more.
Cigarette smoking remains the leading cause of preventable death and morbidity worldwide. Smoking during pregnancy is associated with numerous adverse birth outcomes, including craniofacial and behavioral abnormalities. Although tobacco smoke contains more than 4000 toxic substances, nicotine is addictive and is likely the most teratogenic substance in cigarette smoke. However, much remains to be determined about the effects of embryonic nicotine exposure on behavior and craniofacial development. Therefore, this study evaluated adult social behavior in zebrafish, craniofacial defects, and nicotine metabolism in embryos after embryonic nicotine exposure. Zebrafish embryos were exposed to different doses of nicotine beginning at 6 h post fertilization. To evaluate craniofacial defects, the embryos were collected at 4 days post fertilization and stained with Alizarin Red and Alcian Blue. For behavioral testing, embryos were reared to adulthood. To evaluate nicotine metabolism, cotinine levels were analyzed at various time points. Our findings demonstrate that embryonic exposure to nicotine modifies social behavior in adulthood, causes craniofacial defects with reduced size of craniofacial cartilages, and that zebrafish metabolize nicotine to cotinine, as in humans. Together, our data suggest that zebrafish are useful as a model for studying nicotine-related diseases. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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13 pages, 3398 KiB  
Article
Effect of Embryonic Alcohol Exposure on Craniofacial and Skin Melanocyte Development: Insights from Zebrafish (Danio rerio)
by Parnia Azimian Zavareh, Praneeth Silva, Nuwanthika Gimhani and Devi Atukorallaya
Toxics 2022, 10(9), 544; https://doi.org/10.3390/toxics10090544 - 18 Sep 2022
Cited by 5 | Viewed by 2961
Abstract
Alcohol is a common addictive substance and prenatal alcohol exposure could cause fetal alcohol spectrum disorder (FASD) and can lead to various birth defects. The small teleost zebrafish (Danio rerio) has been identified as a fine animal model in developmental biology [...] Read more.
Alcohol is a common addictive substance and prenatal alcohol exposure could cause fetal alcohol spectrum disorder (FASD) and can lead to various birth defects. The small teleost zebrafish (Danio rerio) has been identified as a fine animal model in developmental biology and toxicological research. Zebrafish models are widely used to study the harmful effects of alcohol and limited studies are available on the craniofacial and skin malformations associated with FASD. The present study attempts to investigate the effect of alcohol on early zebrafish embryonic development. The effects of prenatal alcohol exposure on neural crest cell-derived organ formation, including pharyngeal dentition, palatal bones and skin melanocytes were analysed. Whole-mount cartilage and bone staining and imaging techniques were applied to determine the effects of alcohol on the above-mentioned structures. The tooth size and shape were affected by alcohol exposure, but the number of teeth in the pharyngeal dentition was not affected. Only first-generation teeth showed size differences. The alcohol-exposed ethmoid bone, which is homologous to the human hard palate, was smaller and less dense in cell arrangement compared with the control medial ethmoid bone. The skin pigmentation defects included reduced melanocyte density, melanin contraction, smaller melanocyte surface area and aberrations in melanosome dispersion, revealing that alcohol significantly influenced and downregulated each and every step of the melanocyte developmental process. This descriptive study summarises the effects of alcohol on the development of neural crest cell-derived structures and highlights the importance of zebrafish in studying the phenotypic characteristics of fetal alcohol spectrum disorder. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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14 pages, 1081 KiB  
Communication
Development and Applications of a Zebrafish (Danio rerio) CYP1A-Targeted Monoclonal Antibody (CRC4) with Reactivity across Vertebrate Taxa: Evidence for a Conserved CYP1A Epitope
by Amy L. Anderson, Benjamin D. Dubanksy, Lindsay B. Wilson, Robyn L. Tanguay and Charles D. Rice
Toxics 2022, 10(7), 404; https://doi.org/10.3390/toxics10070404 - 20 Jul 2022
Cited by 2 | Viewed by 2542
Abstract
CYP1A is a heme-thiolate enzyme associated with the cytochrome P4501A1 monooxygenase system and is inducible by a wide variety of xenobiotics and endogenous ligands that bind and activate the aryl hydrocarbon receptor (AHR). The AHR-CYP1A axis is important for detoxification of certain xenobiotics [...] Read more.
CYP1A is a heme-thiolate enzyme associated with the cytochrome P4501A1 monooxygenase system and is inducible by a wide variety of xenobiotics and endogenous ligands that bind and activate the aryl hydrocarbon receptor (AHR). The AHR-CYP1A axis is important for detoxification of certain xenobiotics and for homeostatic balance of endogenous sex hormones, amine hormones, vitamins, fatty acids, and phospholipids. Herein, we generated and described applications of a zebrafish CYP1A-targeted monoclonal antibody (mAb CRC4) that fortuitously recognizes induced CYP1A across vertebrate taxa, including fish, chicken, mouse, rat, and human. We then demonstrated that mAb CRC4 targets a highly conserved epitope signature of vertebrate CYP1A. The unique complimentary determining region (CDR) sequences of heavy and light chains were determined, and these Ig sequences will allow for the expression of recombinant mAb CRC4, thus superseding the need for long-term hybridoma maintenance. This antibody works well for immunohistochemistry (IHC), as well as whole-mounted IHC in zebrafish embryos. Monoclonal antibody CRC4 may be particularly useful for studying the AHR-CYP1A axis in multiple vertebrate species and within the context of Oceans and Human Health research. By using archived samples, when possible, we actively promoted efforts to reduce, replace, and refine studies involving live animals. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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14 pages, 1035 KiB  
Article
Evaluating Phenotypic and Transcriptomic Responses Induced by Low-Level VOCs in Zebrafish: Benzene as an Example
by Chia-Chen Wu, Jessica R. Blount, Alex Haimbaugh, Samantha Heldman, Jeremiah N. Shields and Tracie R. Baker
Toxics 2022, 10(7), 351; https://doi.org/10.3390/toxics10070351 - 27 Jun 2022
Cited by 8 | Viewed by 2480
Abstract
Urban environments are plagued by complex mixtures of anthropogenic volatile organic compounds (VOCs), such as mixtures of benzene, toluene, ethylene, and xylene (BTEX). Sources of BTEX that drive human exposure include vehicle exhaust, industrial emissions, off-gassing of building material, as well as oil [...] Read more.
Urban environments are plagued by complex mixtures of anthropogenic volatile organic compounds (VOCs), such as mixtures of benzene, toluene, ethylene, and xylene (BTEX). Sources of BTEX that drive human exposure include vehicle exhaust, industrial emissions, off-gassing of building material, as well as oil spillage and leakage. Among the BTEX mixture, benzene is the most volatile compound and has been linked to numerous adverse health outcomes. However, few studies have focused on the effects of low-level benzene on exposure during early development, which is a susceptible window when hematological, immune, metabolic, and detoxification systems are immature. In this study, we used zebrafish to conduct a VOC exposure model and evaluated phenotypic and transcriptomic responses following 0.1 and 1 ppm benzene exposure during the first five days of embryogenesis (n = 740 per treatment). The benzene body burden was 2 mg/kg in 1 ppm-exposed larval zebrafish pools and under the detection limit in 0.1 ppm-exposed fish. No observable phenotypic changes were found in both larvae except for significant skeletal deformities in 0.1 ppm-exposed fish (p = 0.01) compared with unexposed fish. Based on transcriptomic responses, 1 ppm benzene dysregulated genes that were implicated with the development of hematological system, and the regulation of oxidative stress response, fatty acid metabolism, immune system, and inflammatory response, including apob, nfkbiaa, serpinf1, foxa1, cyp2k6, and cyp2n13 from the cytochrome P450 gene family. Key genes including pik3c2b, pltp, and chia.2 were differentially expressed in both 1 and 0.1 ppm exposures. However, fewer transcriptomic changes were induced by 0.1 ppm compared with 1 ppm. Future studies are needed to determine if these transcriptomic responses during embryogenesis have long-term consequences at levels equal to or lower than 1 ppm. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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15 pages, 1305 KiB  
Article
Developmental, Behavioral and Transcriptomic Changes in Zebrafish Embryos after Smoke Dye Exposure
by Edward J. Perkins, Kimberly T. To, Lindsey St. Mary, Charles H. Laber, Anthony J. Bednar, Lisa Truong, Robyn L. Tanguay and Natàlia Garcia-Reyero
Toxics 2022, 10(5), 210; https://doi.org/10.3390/toxics10050210 - 22 Apr 2022
Cited by 4 | Viewed by 2604
Abstract
(1) Background: Disperse Blue 14, Disperse Red 9, Solvent Red 169 and Solvent Yellow 33 have been used to color smoke; however, they have not been comprehensively assessed for their potential health hazards. (2) Methods: To assess the effects of these dyes, zebrafish [...] Read more.
(1) Background: Disperse Blue 14, Disperse Red 9, Solvent Red 169 and Solvent Yellow 33 have been used to color smoke; however, they have not been comprehensively assessed for their potential health hazards. (2) Methods: To assess the effects of these dyes, zebrafish embryos were exposed from 6 to 120 h post fertilization (hpf) to 10–55 µM Disperse Red 9, 1–50 µM Solvent Red 169, 7.5–13.5 µM Solvent Yellow 33 or 133–314 µM Disperse Blue 14. Embryos were monitored for adverse effects on gene expression at 48 hpf as well as for mortality, development and behavior at 120 hpf. The dyes were examined for their potential to cross the blood–brain barrier. (3) Results: Solvent Yellow 33 and Disperse Blue 14 impaired development and behavior at all concentrations. Disperse Red 9 impaired behavior at all concentrations and development at all concentrations except for 10 µM. Solvent Red 169 caused no effects. Mortality was only seen in Disperse Blue 14 at 261.5 and 314 µM. Gene expression indicated impacts on neurodevelopment and folate and retinol metabolism as potential mechanisms of toxicity. (4) Conclusions: Smoke dyes have a high potential for causing developmental changes and neurotoxicity and should be examined more closely using comprehensive approaches as used here. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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10 pages, 1385 KiB  
Article
MPTP-Treated Zebrafish Recapitulate ‘Late-Stage’ Parkinson’s-like Cognitive Decline
by Alim A. O. Bashirzade, Sergey V. Cheresiz, Alisa S. Belova, Alexey V. Drobkov, Anastasiia D. Korotaeva, Soheil Azizi-Arani, Amirhossein Azimirad, Eric Odle, Emma-Yanina V. Gild, Oleg V. Ardashov, Konstantin P. Volcho, Dmitrii V. Bozhko, Vladislav O. Myrov, Sofia M. Kolchanova, Aleksander I. Polovian, Georgii K. Galumov, Nariman F. Salakhutdinov, Tamara G. Amstislavskaya and Allan V. Kalueff
Toxics 2022, 10(2), 69; https://doi.org/10.3390/toxics10020069 - 4 Feb 2022
Cited by 13 | Viewed by 4913
Abstract
The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson’s disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental [...] Read more.
The zebrafish is a promising model species in biomedical research, including neurotoxicology and neuroactive drug screening. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) evokes degeneration of dopaminergic neurons and is commonly used to model Parkinson’s disease (PD) in laboratory animals, including zebrafish. However, cognitive phenotypes in MPTP-evoked experimental PD models remain poorly understood. Here, we established an LD50 (292 mg/kg) for intraperitoneal MPTP administration in adult zebrafish, and report impaired spatial working memory (poorer spontaneous alternation in the Y-maze) in a PD model utilizing fish treated with 200 µg of this agent. In addition to conventional behavioral analyses, we also employed artificial intelligence (AI)-based approaches to independently and without bias characterize MPTP effects on zebrafish behavior during the Y-maze test. These analyses yielded a distinct cluster for 200-μg MPTP (vs. other) groups, suggesting that high-dose MPTP produced distinct, computationally detectable patterns of zebrafish swimming. Collectively, these findings support MPTP treatment in adult zebrafish as a late-stage experimental PD model with overt cognitive phenotypes. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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15 pages, 1784 KiB  
Article
Behavioral Effects of Buspirone in Juvenile Zebrafish of Two Different Genetic Backgrounds
by Amira Abozaid and Robert Gerlai
Toxics 2022, 10(1), 22; https://doi.org/10.3390/toxics10010022 - 7 Jan 2022
Cited by 12 | Viewed by 3378
Abstract
Anxiety continues to represent a major unmet medical need. Despite the availability of numerous anxiolytic drugs, a large proportion of patients do not respond well to current pharmacotherapy, or their response diminishes with chronic drug application. To discover novel compounds and to investigate [...] Read more.
Anxiety continues to represent a major unmet medical need. Despite the availability of numerous anxiolytic drugs, a large proportion of patients do not respond well to current pharmacotherapy, or their response diminishes with chronic drug application. To discover novel compounds and to investigate the mode of action of anxiolytic drugs, animal models have been proposed. The zebrafish is a novel animal model in this research. It is particularly appropriate, as it has evolutionarily conserved features, and drug administration can be employed in a non-invasive manner by immersing the fish into the drug solution. The first step in the analysis of anxiolytic drugs with zebrafish is to test reference compounds. Here, we investigate the effects of buspirone hydrochloride, an anxiolytic drug often employed in the human clinic. We utilize two genetically distinct populations of zebrafish, ABSK, derived from the quasi-inbred AB strain, and WT, a genetically heterogeneous wild-type population. We placed juvenile (10–13-day, post-fertilization, old) zebrafish singly in petri dishes containing one of four buspirone concentrations (0 mg/L control, 5 mg/L, 20 mg/L or 80 mg/L) for 1 h, with each fish receiving a single exposure to one concentration, a between subject experimental design. Subsequently, we recorded the behavior of the zebrafish for 30 min using video-tracking. Buspirone decreased distance moved, number of immobility episodes and thigmotaxis, and it increased immobility duration and turn angle in a quasi-linear dose dependent but genotype independent manner. Although it is unclear whether these changes represent anxiolysis in zebrafish, the results demonstrate that behavioral analysis of juvenile zebrafish may be a sensitive and simple way to quantify the effects of human anxiolytic drugs. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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14 pages, 1695 KiB  
Article
Exploring Neurobehaviour in Zebrafish Embryos as a Screening Model for Addictiveness of Substances
by Anne Havermans, Edwin P. Zwart, Hans W. J. M. Cremers, Maarten D. M. van Schijndel, Romy S. Constant, Maja Mešković, Laura X. Worutowicz, Jeroen L. A. Pennings, Reinskje Talhout, Leo T. M. van der Ven and Harm J. Heusinkveld
Toxics 2021, 9(10), 250; https://doi.org/10.3390/toxics9100250 - 7 Oct 2021
Cited by 2 | Viewed by 3151
Abstract
Tobacco use is the leading cause of preventable death worldwide and is highly addictive. Nicotine is the main addictive compound in tobacco, but less is known about other components and additives that may contribute to tobacco addiction. The zebrafish embryo (ZFE) has been [...] Read more.
Tobacco use is the leading cause of preventable death worldwide and is highly addictive. Nicotine is the main addictive compound in tobacco, but less is known about other components and additives that may contribute to tobacco addiction. The zebrafish embryo (ZFE) has been shown to be a good model to study the toxic effects of chemicals on the neurological system and thus may be a promising model to study behavioral markers of nicotine effects, which may be predictive for addictiveness. We aimed to develop a testing protocol to study nicotine tolerance in ZFE using a locomotion test with light-dark transitions as behavioral trigger. Behavioral experiments were conducted using three exposure paradigms: (1) Acute exposure to determine nicotine’s effect and potency. (2) Pre-treatment with nicotine dose range followed by a single dose of nicotine, to determine which pre-treatment dose is sufficient to affect the potency of acute nicotine. (3) Pre-treatment with a single dose combined with acute exposure to a dose range to confirm the hypothesized decreased potency of the acute nicotine exposure. These exposure paradigms showed that (1) acute nicotine exposure decreased ZFE activity in response to dark conditions in a dose-dependent fashion; (2) pre-treatment with increasing concentrations dose-dependently reversed the effect of acute nicotine exposure; and (3) a fixed pre-treatment dose of nicotine induced a decreased potency of the acute nicotine exposure. This effect supported the induction of tolerance to nicotine by the pre-treatment, likely through neuroadaptation. The interpretation of these effects, particularly in view of prediction of dependence and addictiveness, and suitability of the ZFE model to test for such effects of other compounds than nicotine, are discussed. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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11 pages, 1785 KiB  
Article
Differential Modulation of the Central and Peripheral Monoaminergic Neurochemicals by Deprenyl in Zebrafish Larvae
by Marina Bellot, Helena Bartolomé, Melissa Faria, Cristian Gómez-Canela and Demetrio Raldúa
Toxics 2021, 9(6), 116; https://doi.org/10.3390/toxics9060116 - 23 May 2021
Cited by 9 | Viewed by 2904
Abstract
Zebrafish embryos and larvae are vertebrate models increasingly used in translational neuroscience research. Behavioral impairment induced by the exposure to neuroactive or neurotoxic compounds is commonly linked to changes in modulatory neurotransmitters in the brain. Although different analytical methods for determining monoaminergic neurochemicals [...] Read more.
Zebrafish embryos and larvae are vertebrate models increasingly used in translational neuroscience research. Behavioral impairment induced by the exposure to neuroactive or neurotoxic compounds is commonly linked to changes in modulatory neurotransmitters in the brain. Although different analytical methods for determining monoaminergic neurochemicals in zebrafish larvae have been developed, these methods have been used only on whole larvae, as the dissection of the brain of hundreds of larvae is not feasible. This raises a key question: Are the changes in the monoaminergic profile of the whole larvae predictive of the changes in the brain? In this study, the levels of ten monoaminergic neurotransmitters were determined in the head, trunk, and the whole body of zebrafish larvae in a control group and in those treated for 24 h with 5 M deprenyl, a prototypic monoamine-oxidase B inhibitor, eight days post-fertilization. In control larvae, most of the monoaminergic neurochemicals were found at higher levels in the head than in the trunk. Significant changes were found in the distribution of some neurochemicals after deprenyl-treatment, with serotonin and norepinephrine increasing in both the head and the trunk, whereas dopamine, L-DOPA, and homovanillic acid levels were only modulated in the head. In fact, the highly significant increase in dopamine levels observed in the head after deprenyl-treatment was not detected in the whole-body analysis. These results indicate that the analysis of neurotransmitters in the zebrafish larvae whole-body should not be used as a general surrogate of the brain. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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15 pages, 2459 KiB  
Article
Zebrafish Embryonic Exposure to BPAP and Its Relatively Weak Thyroid Hormone-Disrupting Effects
by Sangwoo Lee, Kojo Eghan, Jieon Lee, Donggon Yoo, Seokjoo Yoon and Woo-Keun Kim
Toxics 2020, 8(4), 103; https://doi.org/10.3390/toxics8040103 - 13 Nov 2020
Cited by 4 | Viewed by 3302
Abstract
Safe endocrine-disrupting alternatives for bisphenol A (BPA) are needed because its adverse health effects have become a public concern. Some bisphenol analogues (bisphenol F and S) have been applied, but their endocrine-disrupting potential is either not negligible or weaker than that of BPA. [...] Read more.
Safe endocrine-disrupting alternatives for bisphenol A (BPA) are needed because its adverse health effects have become a public concern. Some bisphenol analogues (bisphenol F and S) have been applied, but their endocrine-disrupting potential is either not negligible or weaker than that of BPA. However, the endocrine-disrupting potential of bisphenol AP (BPAP), another BPA alternative, has not yet been fully assessed. Hence, we evaluated the thyroid hormone (TH)-disrupting potency of BPAP because THs are essential endocrine hormones. Zebrafish embryos were exposed to BPAP (0, 18.2, 43.4, or 105.9 μg/L) for 120 h, and TH levels, the transcription of 16 TH-related genes, the transcriptome, development, and behavior were evaluated. In our study, a decrease in T4 level was observed only at the maximum nonlethal concentration, but significant changes in the T3 and TSHβ levels were not detected. BPAP did not cause significant changes in transcription and gene ontology enrichment related to the TH system. Developmental and behavioral changes were not observed. Despite T4 level reduction, other markers were not significantly affected by BPAP. These might indicate that BPAP has weak or negligible potency regarding TH disruption as a BPA alternative. This study might provide novel information on the TH-disrupting potential of BPAP. Full article
(This article belongs to the Special Issue Fish Models for Human Toxicology)
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