A Quantitative Adverse Outcome Pathway for Embryonic Activation of the Aryl Hydrocarbon Receptor of Fishes by Polycyclic Aromatic Hydrocarbons Leading to Decreased Fecundity at Adulthood

IF 3.6 4区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology and Chemistry Pub Date : 2024-08-02 DOI:10.1002/etc.5964

Jon A. Doering, Justin Dubiel, Eric Stock, Cameron H. Collins, Ian Frick, Hunter M. Johnson, Christopher M. Lowrey-Dufour, Justin G. P. Miller, Zhe Xia, Gregg T. Tomy, Steve Wiseman

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Abstract

Quantitative adverse outcome pathways (qAOPs) describe the response–response relationships that link the magnitude and/or duration of chemical interaction with a specific molecular target to the probability and/or severity of the resulting apical-level toxicity of regulatory relevance. The present study developed the first qAOP for latent toxicities showing that early life exposure adversely affects health at adulthood. Specifically, a qAOP for embryonic activation of the aryl hydrocarbon receptor 2 (AHR2) of fishes by polycyclic aromatic hydrocarbons (PAHs) leading to decreased fecundity of females at adulthood was developed by building on existing qAOPs for (1) activation of the AHR leading to early life mortality in birds and fishes, and (2) inhibition of cytochrome P450 aromatase activity leading to decreased fecundity in fishes. Using zebrafish (Danio rerio) as a model species and benzo[a]pyrene as a model PAH, three linked quantitative relationships were developed: (1) plasma estrogen in adult females as a function of embryonic exposure, (2) plasma vitellogenin in adult females as a function of plasma estrogen, and (3) fecundity of adult females as a function of plasma vitellogenin. A fourth quantitative relationship was developed for early life mortality as a function of sensitivity to activation of the AHR2 in a standardized in vitro AHR transactivation assay to integrate toxic equivalence calculations that would allow prediction of effects of exposure to untested PAHs. The accuracy of the predictions from the resulting qAOP were evaluated using experimental data from zebrafish exposed as embryos to another PAH, benzo[k]fluoranthene. The qAOP developed in the present study demonstrates the potential of the AOP framework in enabling consideration of latent toxicities in quantitative ecological risk assessments and regulatory decision-making. Environ Toxicol Chem 2024;43:2145–2156. © 2024 SETAC

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多环芳香烃对鱼类芳香烃受体的胚胎激活导致成年后繁殖力下降的量化不良后果途径。

定量不良后果途径（qAOPs）描述了反应-反应关系，这种关系将化学物质与特定分子靶点相互作用的程度和/或持续时间与由此产生的与监管相关的顶端毒性的概率和/或严重程度联系起来。本研究首次开发了潜伏毒性 qAOP，表明生命早期暴露会对成年后的健康产生不利影响。具体来说，本研究以现有的 qAOPs 为基础，开发了多环芳烃（PAHs）激活鱼类胚胎期芳烃受体 2（AHR2）导致雌鱼成年后繁殖力下降的 qAOPs：(1) 激活 AHR 导致鸟类和鱼类生命早期死亡；(2) 抑制细胞色素 P450 芳香化酶活性导致鱼类繁殖力下降。以斑马鱼（Danio rerio）为模式物种，以苯并[a]芘为模式多环芳烃，建立了三种相关的定量关系：(1) 成年雌鱼血浆雌激素与胚胎暴露的函数关系；(2) 成年雌鱼血浆卵黄素与血浆雌激素的函数关系；(3) 成年雌鱼的繁殖力与血浆卵黄素的函数关系。第四种定量关系是在标准化体外 AHR 反式激活试验中，将生命早期死亡率作为 AHR2 激活敏感性的函数，以整合毒性当量计算，从而预测暴露于未经测试的多环芳烃的影响。利用斑马鱼胚胎暴露于另一种多环芳烃--苯并[k]荧蒽的实验数据，对由此得出的 qAOP 预测结果的准确性进行了评估。本研究开发的 qAOP 展示了 AOP 框架在定量生态风险评估和监管决策中考虑潜在毒性的潜力。环境毒物化学 2024;00:1-12。© 2024 SETAC.

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来源期刊

Environmental Toxicology and Chemistry 环境科学-毒理学

CiteScore

7.40

自引率

9.80%

发文量

265

审稿时长

3.4 months

期刊介绍： The Society of Environmental Toxicology and Chemistry (SETAC) publishes two journals: Environmental Toxicology and Chemistry (ET&C) and Integrated Environmental Assessment and Management (IEAM). Environmental Toxicology and Chemistry is dedicated to furthering scientific knowledge and disseminating information on environmental toxicology and chemistry, including the application of these sciences to risk assessment.[...] Environmental Toxicology and Chemistry is interdisciplinary in scope and integrates the fields of environmental toxicology; environmental, analytical, and molecular chemistry; ecology; physiology; biochemistry; microbiology; genetics; genomics; environmental engineering; chemical, environmental, and biological modeling; epidemiology; and earth sciences. ET&C seeks to publish papers describing original experimental or theoretical work that significantly advances understanding in the area of environmental toxicology, environmental chemistry and hazard/risk assessment. Emphasis is given to papers that enhance capabilities for the prediction, measurement, and assessment of the fate and effects of chemicals in the environment, rather than simply providing additional data. The scientific impact of papers is judged in terms of the breadth and depth of the findings and the expected influence on existing or future scientific practice. Methodological papers must make clear not only how the work differs from existing practice, but the significance of these differences to the field. Site-based research or monitoring must have regional or global implications beyond the particular site, such as evaluating processes, mechanisms, or theory under a natural environmental setting.

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