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通过吸入途径在小鼠模型中研究多氯联苯混合物Aroclor 1232的跨代毒性。

Transgenerational toxicity of Aroclor 1232 by inhalational route in mouse model.

作者信息

Muthusamy Sivaselvakumar, Narayanan Ramanujam

机构信息

PSG-Center for Molecular Medicine & Therapeutics (PSG-CMMT), PSG Institute of Medical Sciences & Research, Coimbatore, India.

Pharmacology, PSG Institute of Medical Sciences & Research, Coimbatore, India.

出版信息

Toxicol Rep. 2025 Jun 17;15:102072. doi: 10.1016/j.toxrep.2025.102072. eCollection 2025 Dec.

DOI:10.1016/j.toxrep.2025.102072
PMID:40613080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12214260/
Abstract

BACKGROUND

Aroclor 1232 is a commercial mixture of polychlorinated biphenyls with inhalational toxicological implications as it contains semi-volatile congeners like PCB 77, along with highly lipophillic ones like PCB 180. We aimed to assess the trans-generational behavioral toxicities of this complex mixture in mice by inhalational dosing chamber. We also aimed to evaluate the penetrability of PCBs across placental and lactational routes in mice in this study.

METHODS

We assessed the probable route of penetration in the first generation of litters using behavioral scores as surrogate markers of developmental toxicity. We also quantified plasma concentrations of key PCBs and anthropometric parameters for trans-generational comparability.

RESULTS

PCBs are responsible for behavioral toxicities across one generation of mice by hazardous exposures via the inhalational route. Behavioral scores of F1 and F2generation mice indicated as surrogate endpoints that PCBs are concentrated in lactating milk more than placental route in the next generation of mice. No significant lethality or effects on anthropometrical parameters were detected across one generation although the congeners were detected in plasma of the litters when they were 12-14 weeks age.

CONCLUSION

PCBs may pose both indoor and outdoor volatile hazard by inhalational routes and cause behavioral deficits across one generation by transfer via lactational routes. PCB 77 is more evident of penetrating trans-generationally and produces behavioral toxicities in subsequent generations. They definitely carry inhalational hazard in workplaces and outdoor as environmental pollutants and neuroendocrine disruptors.

摘要

背景

氯丹1232是一种多氯联苯的商业混合物,具有吸入毒理学影响,因为它含有像多氯联苯77这样的半挥发性同系物,以及像多氯联苯180这样的高亲脂性同系物。我们旨在通过吸入给药室评估这种复杂混合物对小鼠的跨代行为毒性。在本研究中,我们还旨在评估多氯联苯在小鼠胎盘和哺乳途径中的穿透性。

方法

我们使用行为评分作为发育毒性的替代标志物,评估第一代幼崽中可能的渗透途径。我们还对关键多氯联苯的血浆浓度和人体测量参数进行了量化,以进行跨代比较。

结果

多氯联苯通过吸入途径的有害暴露导致一代小鼠出现行为毒性。F1和F2代小鼠的行为评分作为替代终点表明,在下一代小鼠中,多氯联苯在乳汁中的浓度高于胎盘途径。尽管在幼崽12 - 14周龄时在其血浆中检测到了同系物,但在一代中未检测到明显的致死性或对人体测量参数的影响。

结论

多氯联苯可能通过吸入途径造成室内和室外挥发性危害,并通过哺乳途径传递导致一代出现行为缺陷。多氯联苯77在跨代穿透方面更为明显,并在后代中产生行为毒性。它们无疑作为环境污染物和神经内分泌干扰物在工作场所和室外带来吸入危害。

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本文引用的文献

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Effects of Aryl Hydrocarbon Receptor Deficiency on PCB-77-Induced Impairment of Glucose Homeostasis during Weight Loss in Male and Female Obese Mice.芳香烃受体缺失对雄性和雌性肥胖小鼠减肥过程中 PCB-77 诱导的葡萄糖稳态损伤的影响。
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Fast and parallel determination of PCB 77 and PCB 180 in plasma using ultra performance liquid chromatography with diode array detection: A pharmacokinetic study in Swiss albino mouse.
使用超高效液相色谱-二极管阵列检测法快速并行测定血浆中的多氯联苯77和多氯联苯180:瑞士白化小鼠的药代动力学研究
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Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes.多氯联苯(PCB 101、PCB 153和PCB 180)改变分化的3T3-L1脂肪细胞中的瘦素信号传导和脂质代谢。
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PCBs and OH-PCBs in serum from children and mothers in urban and rural U.S. communities.美国城乡社区儿童和母亲血清中的多氯联苯和 羟基多氯联苯。
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Postnatal exposure to PCB 153 and PCB 180, but not to PCB 52, produces changes in activity level and stimulus control in outbred male Wistar Kyoto rats.产后接触多氯联苯 153 和多氯联苯 180,但不接触多氯联苯 52,会导致雄性 Wistar Kyoto 大鼠的活动水平和刺激控制发生变化。
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