Basics of Dose-Response

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Introduction: You have just moved into your dream house and discover a secret room which you hadn’t noticed before and which escaped the notice of your home inspection. Once you gain access, you discover numerous amber colored bottles with the traditional skull and crossbones logo emblazoned upon the bottles. You’re rightfully concerned.  Is your house now contaminated and are you at risk to live there?  This Tox Topic was developed to help you understand how to think about potential exposure to chemicals.  By understanding these key concepts, you’ll be better prepared to keep yourself and your family safe from harmful exposures.

Let’s start with some key definitions:

Hazard:  A potential source of danger/harm.  A hazard evaluation in toxicology focuses on defining what types of harmful effects could occur and under what circumstances (e.g. ingestion, inhalation, skin contact). Toxicologists create a hazard profile for a chemical by listing all the ways it could potentially cause harm and how much it would take to do so.

Exposure. For a hazard to cause harm, it has to get into, or onto, your body.  You have to be exposed in some way.  Alcohol can be hazardous to your health, but if you don’t drink any alcohol, you aren’t exposed and therefore can’t suffer harm.  Whether you drink a little, or a lot, will influence how much you could be harmed.  The amount you drink is what we define next as the dose.

Dose:  In simplest terms, the amount of a chemical that actually gets into your body is the dose.  And because your body actually responds to the concentration in your blood and tissues, the dose is always expressed relative to your body weight.  In other words, if two people received the exact same total amount of something and one person is twice as big as the other the larger person will have received a lower dose because their body is twice as big.

Scientists use the metric system so you’ll almost always see dose expressed as milligrams (mg) of substance per kilogram (kg) of body weight (bw).  Also, because many times we are exposed in smaller quantities over time, you’ll often see dose expressed as mg/kg of bw per day. Understanding dose is critical because it is the most important determining factor for whether a chemical will cause a harmful reaction. This idea was originally expressed by the Swiss physician Paracelsus (1496-1531):  “Poison is in everything, and no thing is without poison.   The dosage makes it either a poison or a remedy.” Today, we simply say “the dose makes the poison”.

Response: Response is how the body reacts to a chemical. Your body can react to a chemical in different ways depending on the properties of the chemical and the dose.  Toxicologists determine the different ways your body might respond and determine the doses necessary to cause these effects.

To describe the relationship between dose and response, toxicologists use something called the dose-response curve.  While there are many ways to show how responses change with dose, there are two that are most common and that you may find when searching.  In one type the amount of response increases as the dose increases. This allows one to see how much of an effect occurs at a given dose.  For example, if you’re taking a pain reliever the amount of response at different doses helps define how much it takes to get maximum pain relief. If it takes two 500 mg tablets of aspirin for maximum pain relief, it stands to reason that one 500 mg tablet would result in less than maximum pain relief – a fraction (or percentage). While in this example we’re looking at the benefit from a pain reliever, the toxicologist uses this same kind of dose-response curve to determine what dose it takes to cause harmful effects.

The second type of dose-response curve looks at what percentage of a group (people, animals) responds as the dose increases. We know that not all people respond exactly the same way at a given dose.  Using the aspirin example, if two 500 mg tablets of aspirin result in maximum pain relief for you, would the same hold true for 100 other people?  This type of dose-response curve helps to determine what dose to use to benefit the most people. For the toxicologist, this type of dose-response curve helps determine what percentage of people may suffer harm at any specific dose.

The bottom line is that the dose-response relationship is a fundamental tool that toxicologists use to determine just how much it takes to cause harm and how much we can be exposed to without causing harm.

Example of Dose-Response-Alcohol.

According to the 2015 National Survey on Drug Use and Health (NSDUH), 86.4% of people ages 18 or older reported that they drank alcohol at some point in their lifetime; 70.1% reported that they drank in the past year. As anyone who drinks alcohol knows well, the effect (the response) varies greatly with the number of drinks (the dose).

Typical responses to numbers of drinks during a two-hour dinner (response): One (no effect); two (giddy); three (driving impaired); four (drowsy); five (sleep); six (deep sleep); seven (unconscious); eight (labored breathing) and nine (death). Not necessarily accurate and dependent upon the individual as noted above but provided here as different response(s) to increasing the dose in a fixed period of time. The following curve illustrates an increasing response to increasing the dose of alcohol.

Lethal Dose of Alcohol. Unfortunately accidental fatal alcohol poisoning does occur.  The LD50 for alcohol in people is about 5-8 grams per kilogram of body weight.  For a 150 pound person that would be approximately 30 drinks (1 drink is one 12 oz beer, or one glass of wine, or 1 cocktail) in a relatively short period of time (a couple of hours). In other words, if a room full of average sized people drank 30 drinks in two hours, about half of them would likely die.  For perspective, most people would be legally intoxicated after 4 drinks in two hours.

Summary:  Because hazard, exposure, dose and response are terms commonly used by toxicologists to describe the safe use of chemicals it is important for everyone concerned about chemical exposures to understand what they mean and how you can use them to understand safe exposure.

Additional Information:

For additional perspective we recommend the following

Other Tox Topics on this Website:

Human Health Risk Assessment

Videos:

Is it Safe?  Evaluating Chemical Risks.  TEF’s award winning video is also available with Spanish, Japanese and Korean subtitling.

Making Sense of Dose-Response.  A Risk Bites video by Dr. Andrew Maynard.