双语化学辞典Chem Lexicon
概念 · 实验技术 · 毒理学 Laboratory techniques · Toxicology

半数致死量Median lethal dose

拼音Pinyin bàn shù zhì sǐ liàng 别名Also LD50;半数致死浓度 LC50;LD50;LC50

定义Definition

半数致死量(LD₅₀)是指在规定条件下,一次给药后能使一组实验动物死亡一半所需的剂量,通常以每千克体重的毫克数(mg/kg)表示。对于吸入暴露,相应指标为半数致死浓度(LC₅₀)。LD₅₀ 越小,毒性越大。

The median lethal dose, LD₅₀, is the single dose that kills half of a group of test animals under specified conditions, usually expressed in milligrams per kilogram of body weight. For inhalation the equivalent is the median lethal concentration, LC₅₀. The lower the LD₅₀, the more toxic the substance.

原理与意义Principle and meaning

剂量-死亡率关系通常呈 S 形曲线,用概率单位法等统计方法求出 50% 死亡对应的剂量。LD₅₀ 必须注明动物种类、给药途径(经口、经皮、静脉)和观察时间。例如大鼠经口 LD₅₀:食盐约 3000 mg/kg,咖啡因约 192 mg/kg,尼古丁约 50 mg/kg,氰化钾约 5–10 mg/kg,肉毒杆菌毒素约 1 ng/kg(已知毒性最强的物质之一)。GHS 急性毒性按经口 LD₅₀ 分为 5 类:≤5、≤50、≤300、≤2000、≤5000 mg/kg。

Mortality against dose usually follows an S-shaped curve, and statistical methods such as probit analysis give the dose for 50% mortality. An LD₅₀ must state the species, route (oral, dermal, intravenous) and observation period. Oral LD₅₀ values in rats are, for example, about 3000 mg/kg for table salt, 192 mg/kg for caffeine, 50 mg/kg for nicotine, 5–10 mg/kg for potassium cyanide, and about 1 ng/kg for botulinum toxin, among the most toxic substances known. GHS acute oral toxicity categories are ≤5, ≤50, ≤300, ≤2000 and ≤5000 mg/kg.

由来Origin

1927 年英国药理学家约翰·威廉·特雷万为了标准化洋地黄、胰岛素等生物药品的效价而提出 LD₅₀ 概念。“剂量决定毒性”这一思想可追溯到 16 世纪的帕拉塞尔苏斯:“所有物质都是毒物,没有不是毒物的,只有剂量决定了一种东西不是毒物。”

In 1927 the British pharmacologist John William Trevan introduced the LD₅₀ to standardise the potency of biological medicines such as digitalis and insulin. The idea that the dose makes the poison goes back to Paracelsus in the sixteenth century, who held that all substances are poisons and only the dose distinguishes a poison from a remedy.

局限与替代Limits and alternatives

LD₅₀ 只反映急性致死毒性,不能反映慢性毒性、致癌性和生殖毒性;不同物种之间差异很大,外推到人有不确定性;传统测定需要大量动物。出于动物福利考虑,经合组织(OECD)已推广固定剂量法、急性毒性分级法和上下增减剂量法,并鼓励体外替代方法。

LD₅₀ reflects only acute lethality, not chronic toxicity, carcinogenicity or reproductive effects; species differ widely, so extrapolation to humans is uncertain; and classical tests use many animals. For animal welfare the OECD now promotes the fixed-dose procedure, the acute toxic class method and the up-and-down procedure, and encourages in-vitro alternatives.

年表Timeline

  • 约 1538

    帕拉塞尔苏斯提出剂量决定毒性

    Paracelsus says the dose makes the poison

  • 1927

    特雷万提出 LD₅₀

    Trevan introduces the LD₅₀

  • 2002

    OECD 删除经典 LD₅₀ 测试指南 401

    The OECD deletes classical LD₅₀ test guideline 401