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哈兰·斯普拉格·道利(Hsd:Sprague Dawley® SD®)大鼠母鼠及其后代的口服脱氧雪腐镰刀菌烯醇毒性

Oral deoxynivalenol toxicity in Harlan Sprague Dawley (Hsd:Sprague Dawley® SD®) rat dams and their offspring.

作者信息

Huang Madelyn C, Furr Johnathan R, Robinson Veronica G, Betz Laura, Shockley Keith, Cunny Helen, Witt Kristine, Waidyanatha Suramya, Germolec Dori

机构信息

Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Southern Research, Birmingham, AL, USA.

出版信息

Food Chem Toxicol. 2021 Feb;148:111963. doi: 10.1016/j.fct.2020.111963. Epub 2020 Dec 31.

Abstract

There is widespread human exposure to deoxynivalenol (DON), a fungal mycotoxin found globally in many grain-based foods and animal feed. Acute exposures to high levels of DON are associated with gastrointestinal effects and emesis in humans and some animals, but the effects of low-dose exposures throughout the lifetime, a more likely exposure scenario in humans, are understudied. Therefore, this study was designed to identify doses of DON that could be used to evaluate long-term toxicity following perinatal exposure. Time-mated Harlan Sprague Dawley (Hsd:Sprague Dawley® SD®) rats were administered 0, 0.03, 0.1, 0.3, 1, or 3 mg/kg/day of DON once daily via gavage starting on gestational day 6 through postnatal day (PND) 27. F animals were administered the same dose as their respective dams via gavage starting on PND 12 until PND 27. Animals were euthanized on PND 28. DON had no effect on maternal body weight or feed consumption at any dose. Findings were limited to the 3 mg/kg/day group: F females had smaller live litter sizes than controls and F pups had lower body weight (4-13%) compared to controls. By PND 28, F body weight, after adjustments for litter effects, was 10-13% lower than controls. Blood samples obtained on PND 28 showed no increases in frequencies of micronucleated immature erythrocytes in either F or F animals. In summary, doses of DON up to 3 mg/kg/day did not affect maternal survival or body weight. Doses of 3 mg/kg/day resulted in slight toxicity manifested as decreased body weight in the offspring. The no-observed effect level was 1 mg/kg/day.

摘要

脱氧雪腐镰刀菌烯醇(DON)在人类中广泛存在,这种真菌毒素在全球许多谷物类食品和动物饲料中都能找到。人类和一些动物急性接触高剂量的DON会出现胃肠道反应和呕吐,但对于人类更可能出现的在整个生命周期中低剂量接触DON的影响,研究较少。因此,本研究旨在确定可用于评估围产期接触DON后长期毒性的剂量。从妊娠第6天开始至出生后第27天(PND),对同期受孕的哈兰·斯普拉格·道利(Hsd:Sprague Dawley® SD®)大鼠每天经口灌胃给予0、0.03、0.1、0.3、1或3毫克/千克/天的DON。从出生后第12天开始至出生后第27天,对F代动物经口灌胃给予与其各自母鼠相同剂量的DON。在出生后第28天对动物实施安乐死。任何剂量的DON对母鼠体重或采食量均无影响。研究结果仅限于3毫克/千克/天组:F代雌性动物的活产仔数比对照组少,F代幼崽的体重比对照组低(4 - 13%)。到出生后第28天,经窝效应调整后,F代动物的体重比对照组低10 - 13%。在出生后第28天采集的血样显示,F代动物或F代幼崽中微核未成熟红细胞的频率均未增加。总之,高达3毫克/千克/天的DON剂量不会影响母鼠的存活或体重。3毫克/千克/天的剂量导致了轻微毒性,表现为后代体重下降。未观察到有害作用水平为1毫克/千克/天。

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