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环境健康中的生命历程考量:低于成人急性效应水平剂量的软骨藻酸的发育神经毒性

Life Course Considerations in Environmental Health: Developmental Neurotoxicity of Domoic Acid at Doses Below Acute Effect Levels in Adult Humans.

作者信息

Campbell Marlissa A, Murphy Shannon R, Klasing Susan A, Niknam Yassaman, Iyer Poorni, Stanton Beckye, Zeise Lauren

机构信息

Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Sacramento, California, USA.

出版信息

Birth Defects Res. 2024 Dec;116(12):e2419. doi: 10.1002/bdr2.2419.

Abstract

BACKGROUND

Current US federal action levels for domoic acid (DA) in seafood are based on acute toxicity observed in exposed adult humans. Life course considerations have not been incorporated. The potential for developmental neurotoxicity (DNT) at permissible DA levels has previously been noted, but not methodically assessed.

METHODS

Studies of DNT following DA exposure in experimental and wild animals were identified through a comprehensive search strategy. Evidence from papers meeting inclusion criteria was evaluated for specific outcomes reported for doses at which adverse effects were observed. Exposure levels associated with DNT were compared with those known to cause adult toxicity. The findings are discussed in the context of the well-characterized mechanism of DA neurotoxicity, as well as the toxicokinetics of DA across species and life stages.

CONCLUSIONS

DNT outcomes were reported with a no observed adverse effect level (NOAEL) 10 times lower than the NOAEL of 0.75 mg DA/kg for acute effects in adults. Apart from reviewing current regulatory action levels, public health outreach messaging to health care professionals and sensitive populations, such as pregnant or breastfeeding women, should be considered as a means of increasing awareness about risk for DNT from consumption of potentially DA-contaminated seafood.

摘要

背景

美国目前针对海产品中软骨藻酸(DA)的联邦行动水平是基于在成年暴露人群中观察到的急性毒性。尚未纳入生命历程相关考量。此前已注意到在允许的DA水平下存在发育性神经毒性(DNT)的可能性,但未进行系统评估。

方法

通过全面的检索策略确定了在实验动物和野生动物中DA暴露后DNT的研究。对符合纳入标准的论文中报告的特定结果进行了评估,这些结果针对观察到不良反应的剂量。将与DNT相关的暴露水平与已知会导致成年毒性的水平进行了比较。研究结果在DA神经毒性的充分表征机制以及DA在不同物种和生命阶段的毒代动力学背景下进行了讨论。

结论

报告的DNT结果的未观察到不良反应水平(NOAEL)比成年急性效应的0.75毫克DA/千克的NOAEL低10倍。除了审查当前的监管行动水平外,向医疗保健专业人员和敏感人群(如孕妇或哺乳期妇女)进行公共卫生宣传信息传递,应被视为提高对食用可能受DA污染的海产品导致DNT风险认识的一种手段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ee7/11639046/700d187a0348/BDR2-116-e2419-g001.jpg

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