Abstract：
BACKGROUND: To protect from toxicity at supra-essential doses of selenium, it is important to determine dose levels at which adverse effects occur.
METHODS: We identified relevant literature on the repeated dosage of selenium and extracted dose descriptors on reported endpoints, except on genotoxicity/carcinogenicity.
RESULTS: Selenium forms with toxicological data were organic ones: selenomethionine, selenocystine/selenocysteine; and inorganic ones, including selenite (SeO32-), selenate (SeO42-), selenium sulphide (SeS2), selenide (Se2-) and selenium nanoparticles. Clinical signs of selenium toxicity in humans include a garlicky-smelling breath, hair loss, and nail changes. One human study showed increased mortality following daily ingestion of 300 µg Se per day for 5 years, equal to a lowest-observed-adverse-effect level (LOAEL) of ∼4.3 µg/kg bw/days. The corresponding no-observed-adverse-effect level (NOAEL) was ∼2.9 µg Se/kg bw/day. One study reported an increased risk of type 2 diabetes after ∼2.9 µg Se/kg bw/day, but other studies with similar doses found no increases in mortality or incidence of type 2 diabetes. NOAELs on affected body weight in animal studies were 0.24-1.2 mg Se/kg bw/day. Other endpoints of selenium toxicity in animals include hepatotoxicity with a NOAEL as low as 2 µg/kg bw/day in rats, as well as gastrointestinal, cardiovascular, and reproductive toxicities with NOAELs of 0.6 (gastrointestinal), 0.08, and 0.4 (cardiovascular) and ≥ 0.04 mg Se/kg bw/day (reproductive), respectively.
CONCLUSIONS: Dose descriptors describing selenium toxicity were as low as 2-3 µg Se/kg bw/day.
METHODS: We identified relevant literature on the repeated dosage of selenium and extracted dose descriptors on reported endpoints, except on genotoxicity/carcinogenicity.
RESULTS: Selenium forms with toxicological data were organic ones: selenomethionine, selenocystine/selenocysteine; and inorganic ones, including selenite (SeO32-), selenate (SeO42-), selenium sulphide (SeS2), selenide (Se2-) and selenium nanoparticles. Clinical signs of selenium toxicity in humans include a garlicky-smelling breath, hair loss, and nail changes. One human study showed increased mortality following daily ingestion of 300 µg Se per day for 5 years, equal to a lowest-observed-adverse-effect level (LOAEL) of ∼4.3 µg/kg bw/days. The corresponding no-observed-adverse-effect level (NOAEL) was ∼2.9 µg Se/kg bw/day. One study reported an increased risk of type 2 diabetes after ∼2.9 µg Se/kg bw/day, but other studies with similar doses found no increases in mortality or incidence of type 2 diabetes. NOAELs on affected body weight in animal studies were 0.24-1.2 mg Se/kg bw/day. Other endpoints of selenium toxicity in animals include hepatotoxicity with a NOAEL as low as 2 µg/kg bw/day in rats, as well as gastrointestinal, cardiovascular, and reproductive toxicities with NOAELs of 0.6 (gastrointestinal), 0.08, and 0.4 (cardiovascular) and ≥ 0.04 mg Se/kg bw/day (reproductive), respectively.
CONCLUSIONS: Dose descriptors describing selenium toxicity were as low as 2-3 µg Se/kg bw/day.
摘要：
背景：为了防止超必需剂量硒的毒性，确定不良反应发生的剂量水平很重要。
方法：我们确定了有关硒重复剂量的相关文献以及所报告终点的提取剂量描述符，除了遗传毒性/致癌性。
结果：具有毒理学数据的硒形式是有机形式：硒代蛋氨酸，硒代半胱氨酸/硒代半胱氨酸；和无机物，包括亚硒酸盐(SeO32-)，硒酸盐(SeO42-)，硫化硒（SeS2），硒化物(Se2-)和硒纳米颗粒。人类硒中毒的临床症状包括刺耳的气味，脱发,指甲的变化。一项人体研究表明，每天摄入300µg硒持续5年，死亡率增加，等于观察到的最低不良反应水平(LOAEL)约4.3微克/千克体重/天。相应的未观察到的不良反应水平（NOAEL）为~2.9微克硒/千克体重/天。一项研究报告，2型糖尿病的风险增加后~2.9微克硒/千克体重/天，但其他类似剂量的研究未发现2型糖尿病的死亡率或发病率增加.动物研究中受影响体重的NOAELs为0.24-1.2mgSe/kgbw/天。动物中硒毒性的其他终点包括肝脏毒性，大鼠的NOAEL低至2µg/kgbw/天，以及胃肠道，心血管,和生殖毒性，NOAEL为0.6（胃肠道），0.08，和0.4（心血管）和≥0.04毫克硒/千克体重/天（生殖），分别。
结论：描述硒毒性的剂量描述符低至2-3µgSe/kgbw/天。
方法：我们确定了有关硒重复剂量的相关文献以及所报告终点的提取剂量描述符，除了遗传毒性/致癌性。
结果：具有毒理学数据的硒形式是有机形式：硒代蛋氨酸，硒代半胱氨酸/硒代半胱氨酸；和无机物，包括亚硒酸盐(SeO32-)，硒酸盐(SeO42-)，硫化硒（SeS2），硒化物(Se2-)和硒纳米颗粒。人类硒中毒的临床症状包括刺耳的气味，脱发,指甲的变化。一项人体研究表明，每天摄入300µg硒持续5年，死亡率增加，等于观察到的最低不良反应水平(LOAEL)约4.3微克/千克体重/天。相应的未观察到的不良反应水平（NOAEL）为~2.9微克硒/千克体重/天。一项研究报告，2型糖尿病的风险增加后~2.9微克硒/千克体重/天，但其他类似剂量的研究未发现2型糖尿病的死亡率或发病率增加.动物研究中受影响体重的NOAELs为0.24-1.2mgSe/kgbw/天。动物中硒毒性的其他终点包括肝脏毒性，大鼠的NOAEL低至2µg/kgbw/天，以及胃肠道，心血管,和生殖毒性，NOAEL为0.6（胃肠道），0.08，和0.4（心血管）和≥0.04毫克硒/千克体重/天（生殖），分别。
结论：描述硒毒性的剂量描述符低至2-3µgSe/kgbw/天。
