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经饲料给药暴露的 Hsd:Sprague Dawley SD 大鼠中磷酸三 (氯丙基)酯的发育免疫毒性研究

英文原题:Developmental immunotoxicity study of tris(chloropropyl) phosphate in Hsd:Sprague Dawley SD rats exposed through dosed feed.

查看英文原题

Developmental immunotoxicity study of tris(chloropropyl) phosphate in Hsd:Sprague Dawley SD rats exposed through dosed feed.

PubMed 2025/05/01(内容时间) Toxicol Sci Q1 · IF 5.2(JCR 2025)

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中文摘要

磷酸三(氯丙基)酯(TCPP)是一种有机磷阻燃剂,通常用作消费品和商业产品中多溴联苯醚的替代品。已有研究表明,阻燃剂可在体内和体外调节免疫功能,并且有证据表明至少某些相关化合物如有机磷农药可引起发育免疫毒性。发育免疫毒理学研究通过在饲料中给予怀孕的Hsd:Sprague Dawley SD大鼠0、2500、5000或10,000 ppm TCPP,从妊娠第6天持续至出生后第28天断奶。F1子代持续经饲料暴露于TCPP,直至16至21周龄时实施安乐死并进行发育免疫毒性评估。在F1成年大鼠中评估了固有免疫、体液免疫和细胞介导的免疫功能。在10,000 ppm处理组中,雄性和雌性F1大鼠对绵羊红细胞的抗体形成细胞(AFCs)反应降低,但同时伴有体重降低。在暴露于5000 ppm的雄性大鼠中,AFC反应也显著降低,而该剂量对体重仅有中度影响。TCPP暴露影响了无刺激状态下的基线T细胞增殖;然而,该变化与免疫毒性风险的相关性尚不清楚。TCPP暴露未影响细胞毒性T淋巴细胞活性。仅在血液学、固有NK细胞功能和脾脏免疫细胞群分布方面观察到轻微且不一致的处理相关效应。

综上所述,这些数据表明TCPP在发育期暴露后具有影响体液免疫反应的潜在可能。

展开英文摘要原文

Tris(chloropropyl) phosphate (TCPP) is a member of organophosphate flame retardants used commonly as a replacement for polybrominated diphenyl ethers in consumer and commercial products. Flame retardants have been shown to modulate immune function in vivo and in vitro and there is evidence that at least some related compounds such as organophosphate pesticides can cause developmental immunotoxicity. Developmental immunotoxicology studies were conducted by administering 0, 2500, 5000, or 10,000 ppm TCPP in feed to pregnant Hsd:Sprague Dawley SD rats from gestation day 6 through weaning on postnatal day 28. Feed exposure to TCPP was continued in the F1 offspring until terminal euthanasia at 16 to 21 weeks of age when assessments for developmental immunotoxicity were conducted. Innate, humoral, and cell-mediated immune function were assessed in the F1 adults.

The antibody-forming cells (AFCs) response to sheep red blood cells was reduced in male and female F1 rats in the 10,000 ppm treatment group but coincided with reduced bodyweights. The AFC response was also significantly reduced in male rats exposed to 5000 ppm where only moderate effects on bodyweights occurred. TCPP exposure affected baseline T-cell proliferation without stimulation; however, the relevance of this change for immunotoxicity risk is unknown.

TCPP exposure did not affect cytotoxic T-lymphocyte activity. Only minor and inconsistent treatment-related effects on hematology, innate NK cell function, and immune cell population distributions in the spleen were observed. Taken together, these data indicate that TCPP has the potential to impact humoral immune responses following developmental exposure.

论文信息

作者
Johnson VJ、Ryan K、Luster MI、Pandiri A、Hobbie K、Cora M、Shockley KR、Burleson GR
第一作者单位
Burleson Research Technologies, Inc, Morrisville, NC 27560, United States.United States
通讯作者单位
Division of Translational Toxicology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, United States.United States
文献类型
美国政府(非公共卫生署)资助研究 · 美国 NIH 资助研究
期刊
Toxicological sciences : an official journal of the Society of Toxicology2025 May 1
原文标识
PubMed 39908456 · DOI 10.1093/toxsci/kfaf006