8.12 - Lethal Dose 50% (LD50)

Learning Objectives

I. Dose Response Studies and $LD_{50}$ Definition

• A dose response study is an experiment that exposes a model organism (a mouse, small rodent, amphibian, reptile, or sometimes plants) to a specific chemical in order to measure the response.
• The dose (concentration) is the independent variable.
• The response (outcome) is the dependent variable, and typically measures death or impairment.

• $LD_{50}$ stands for lethal dosage 50. It’s the dosage or concentration that will kill 50% of the organisms in the study.
• For example, if half of the mice in a study die at a dose of 20 milligrams of a chemical per kilogram of body mass, that chemical’s $LD_{50}$ for mice is 20 mg/kg.

• Lower $LD_{50}$ means more toxic: A chemical with a low $LD_{50}$ kills half the test animals at a small dose. For example, the oral $LD_{50}$ in rats is about 192 mg/kg for caffeine and about 3,000 mg/kg for table salt, so by this measure caffeine is about 16 times more toxic than salt ($3{,}000 \div 192 \approx 16$).

II. Units of $LD_{50}$

• $LD_{50}$ data is usually expressed as some kind of mass per mass of body, like milligrams per kilogram of body mass.

• It can also be measured as:
• Parts per million (PPM) when looking at concentration in air or water.
• Mass per volume when measuring concentrations in food or blood, like micrograms per deciliter for blood lead levels.

• Using $LD_{50}$ in a calculation: Multiply the $LD_{50}$ by body mass to find the dose that would kill half of a group of animals that size.
• A pesticide has an $LD_{50}$ of 200 mg/kg in rats. For a 0.25 kg rat: $200 \text{ mg/kg} \times 0.25 \text{ kg} = 50 \text{ mg}$.
• If people responded the same way, a 70 kg adult’s $LD_{50}$ dose would be $200 \text{ mg/kg} \times 70 \text{ kg} = 14{,}000 \text{ mg}$, or 14 g.

III. Application to Human Health and Study Limits

• It’s unethical to perform dose response studies on humans.

• To set acceptable pollutant levels for humans, scientists use data from model organisms, usually mice and rats.

• Scientists typically take the $LD_{50}$ (or $ED_{50}$) level determined in rodents and divide it by 1,000, or a similar safety factor, to account for size differences and to stay extremely cautious.

• Example: With a safety factor of 1,000, the 200 mg/kg $LD_{50}$ above becomes a limit of $200 \div 1{,}000 = 0.2$ mg/kg. For a 70 kg adult, that’s $0.2 \text{ mg/kg} \times 70 \text{ kg} = 14 \text{ mg}$.

• A limitation of these studies is that they’re usually acute (short-term), which means they can’t really capture long-term developmental issues.

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