Doepker Candace L, Heintz Melissa M, van de Ligt Jennifer, Wikoff Daniele S
ToxStrategies, Inc., Newport, KY 41071, USA.
ToxStrategies, Inc., Asheville, NC 28801, USA.
Transl Anim Sci. 2021 Oct 18;5(4):txab203. doi: 10.1093/tas/txab203. eCollection 2021 Oct.
Calcium nitrate has been reported to benefit reproductive outcomes in sows and their offspring when administered via the feed (15 to 19 mg/kg-body weight [bw]/day) during the periparturient period. Traditionally, dietary nitrate had been considered a methemoglobinemia (MetHb) risk in swine. Similar hazard concerns have existed in humans, but a recent benefit/risk analysis established that nitrate levels associated with well-recognized health benefits outweigh potential risks. A similar benefit/risk perspective in swine was lacking and challenged by sparse published hazard data, often referenced within larger reviews related to all livestock. The objective of this review was to better characterize the potential for adverse health and performance effects reported in the literature for swine consuming nitrate and to provide metrics for evaluating the reliability of the studies reviewed. Supplemental exposure via feed or drinking water was considered for any life stage, dose, and exposure duration. More than 30 relevant studies, including case reports and reviews, examined calcium, potassium, sodium, or unspecified nitrate salts at doses up to 1,800 mg nitrate/kg-bw/day for exposures ranging from 1 to 105 d. The studies primarily evaluated weight gain, blood methemoglobin levels, or vitamin A homeostasis in sows or growing swine. An extensive review of the literature showed reports of adverse effects at low nitrate doses to be of low reliability. Conversely, reliable studies corroborate nitrate intake from feed or drinking water at levels equal to or greater than the European Food Safety Authority's no-observed-adverse-effect level (NOAEL) for swine of 410 mg nitrate/kg-bw/day, with no MetHb or other adverse effects on reproduction, growth, or vitamin A levels. Using a weight-of-evidence evaluation, we have moderate-to-high confidence that the NOAEL for nitrate supplementation in swine is likely between 600 and 800 mg/kg-bw/day. These levels are several-fold higher than dietary nitrate concentrations (19 mg/kg-bw/day) that are known to benefit birth outcomes in sows. This review elucidates the quality and reliability of the information sources historically used to characterize nitrate in swine feed as a contaminant of concern. Results from this evaluation can assist risk managers (e.g., regulatory officials and veterinarians) in consideration of proposed benefits as well as reassuring swine producers that low-level nitrate supplementation is not anticipated to be a concern.
据报道，在围产期通过饲料（15至19毫克/千克体重/天）给母猪及其后代投喂硝酸钙，对繁殖性能有好处。传统上，日粮中的硝酸盐被认为会使猪有高铁血红蛋白血症（MetHb）风险。人类也存在类似的风险担忧，但最近的一项效益/风险分析表明，与公认的健康益处相关的硝酸盐水平超过了潜在风险。猪的类似效益/风险观点尚缺，且已发表的危害数据稀少，在与所有家畜相关的较大综述中常被引用，这对该观点构成了挑战。本综述的目的是更好地描述文献中报道的猪摄入硝酸盐对健康和生产性能的潜在不良影响，并提供评估所审查研究可靠性的指标。考虑了任何生命阶段、剂量和暴露持续时间通过饲料或饮用水进行的补充暴露。30多项相关研究，包括病例报告和综述，研究了钙、钾、钠或未指明的硝酸盐，剂量高达1800毫克硝酸盐/千克体重/天，暴露时间为1至105天。这些研究主要评估了母猪或生长猪的体重增加、血液高铁血红蛋白水平或维生素A稳态。对文献的广泛综述表明，低硝酸盐剂量下不良影响的报告可靠性较低。相反，可靠的研究证实，从饲料或饮用水中摄入的硝酸盐水平等于或高于欧洲食品安全局规定的猪的无观察到不良影响水平（NOAEL），即410毫克硝酸盐/千克体重/天，且对高铁血红蛋白或繁殖、生长或维生素A水平没有其他不良影响。通过证据权重评估，我们有中度到高度的信心认为，猪补充硝酸盐的NOAEL可能在600至800毫克/千克体重/天之间。这些水平比已知对母猪产仔结果有益的日粮硝酸盐浓度（19毫克/千克体重/天）高出几倍。本综述阐明了历史上用于将猪饲料中的硝酸盐描述为令人担忧的污染物的信息来源的质量和可靠性。该评估结果可帮助风险管理者（如监管官员和兽医）考虑拟议的益处，并让养猪生产者放心，低水平的硝酸盐补充预计不会成为问题。
