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THINK ABOUT IT

Poisonous snakebites are medical emergencies. The venom from the bite is very toxic and can be deadly, especially for small children or small animals such as rabbits and mice. However, tiny amounts of snake venom have been used therapeutically as a medicine to control high blood pressure. How much snake venom is toxic and how much is therapeutic?

How much is too much of a substance?

To answer this question, you will explore

EXPLORING THE TOPIC

How Toxicity Is Measured

You have probably been warned about the dangers of dozens of different substances, from pesticides to poisonous wild mushrooms. You know better than to drink your shampoo or rub gasoline on your skin. But how is toxicity determined in the first place? And how is it that some things that are good for you, like vitamin tablets, can be toxic or even lethal in high doses?

MEASURING TOXICITY

For our safety, scientists try to determine the toxicity of the products we buy and the substances we come in contact with. Sometimes, they find the toxicity accidentally, when a person is exposed to a harmful substance. Other times, it takes a great deal of evidence before it is determined that a substance is toxic. This was the case with lead-based paints.

It is clearly not a good idea to determine how toxic something is by purposefully exposing humans. Yet it is vital to know how much of a particular substance is dangerous. So, toxicities of most substances are measured by exposing laboratory animals to toxic substances. Typically, rats or mice (sometimes rabbits, dogs, or monkeys) are used. The harm that might be done to the animals must be carefully weighed against potential harm to humans if the toxicities of substances, such as medicines, are unknown.

One way to measure toxicity is to measure the lethal dose of a substance, the amount of substance that can cause death. The LD₅₀ of a substance is the amount of a substance that causes the death of half, or 50%, of the animals exposed to it.

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The table provides the LD₅₀’s for several common substances in grams, milligrams, or micrograms (mcg) of substance per kilogram of body mass. A microgram is one millionth of a gram.

Notice the wide range of doses—from grams, to milligrams (thousandths of a gram), to micrograms (millionths of a gram). A small LD₅₀ indicates that it does not take very much of the substance to produce ill effects. Substances with small LD₅₀’s should definitely be avoided. Snake venom is one of the most dangerous toxins in the table, with an LD₅₀ of 25.0 mcg/kg, while sugar, with an LD₅₀ of 30 g/kg is one of the safer substances.

DOSAGE DETERMINES TOXICITY

You may be surprised to see lethal doses for substances like sugar and aspirin. These substances are usually considered beneficial. However, everything is toxic in a large enough dose, even life-sustaining substances like water and oxygen. And scientists have discovered that many highly toxic substances also have therapeutic value. Botulinum toxin (Botox) can help patients suffering from cerebral palsy. A very large protein isolated from the venom of the blue scorpion has been discovered to inhibit certain cancer tumors.

Relationship to Body Weight

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You may be wondering how testing a substance on very small animals, like rats, will determine whether it is toxic to a larger mammal, such as a human. To take size into account, the LD₅₀ is reported in milligrams of substance per kilogram of body weight, mg/kg. That way the lethal dose can be estimated for a mammal of any size.

Testing lab animals gives us only an approximate range for safety. Our bodies differ in many ways from the bodies of rats or rabbits. And it may seem particularly unkind to subject animals to testing. However, the alternative would be to risk human life with untested medications. Imagine if the safety of products on store shelves had never been confirmed in any way.

[For a review of this math topic, see MATH Spotlight: Dimensional Analysis on page A-16.]

LESSON SUMMARY

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How much is too much of a substance?

Every substance on the planet is a potential toxin. By the same token, many substances that are considered toxic have health benefits when taken in the correct dose. Thus, toxicity is determined by dose. Scientists use a variety of methods to measure toxicity. One measurement is called the LD₅₀. This is the amount of a substance that kills 50% of animals exposed to it. It is commonly expressed in milligrams of substance per kilogram of body weight. A low LD₅₀ means a more toxic substance.