The Dose Makes the Poison, But Just How Much is Safe?
Stories about chemicals that might be harming us are frequently in the news and our social media feeds. Sometimes you’ll encounter phrases like “above the safe level”. Or, you may see terms like reference dose (RfD), acceptable daily intake (ADI), or maximum contaminant level (MCL), and others. These terms can all be very confusing. However, it is our goal that this blog post will help you to understand that these terms all have the same goal of protecting human health and are derived in very similar ways. Importantly, we’re talking about amounts that will not cause any type of harm over a lifetime of exposure, or what we call chronic exposure. This contrasts with determining how much it takes to cause someone to die from a short duration, high dose, exposure—sometimes referred to as acute poisoning.
Animals, Tissues, Cells and Humans
Everything we know about how chemicals can affect health comes from four basic kinds of information: (1) studies with whole animals (exposed through food, water, air or skin); (2) studies exposing tissues isolated from an animal; (3) studies exposing cells taken from animals and humans; or (4) studies of human populations that have been exposed to a chemical through work or everyday life (this is called epidemiology).
One important goal of these studies is to identify the amount where we can’t find any effect. Importantly, we always look for the most sensitive adverse effect—the harm that occurs at the lowest dose. We also conduct tests in a way that helps determine if there are any especially sensitive subpopulations (for example, children vs adults, or the developing fetus). Once we figure out the amount that doesn’t cause an adverse effect, we need to translate that to humans.
Safe Levels for Chemicals with Thresholds
When we determine the dose below which no harm occurs in laboratory animals, we don’t just use that value. Importantly, we always err on the side of caution and assume humans are going to be more sensitive. While we know humans are not always more sensitive than lab animals, we can’t always be sure. So, to determine the safe amount for people we lower the dose that would be considered safe based on animal and lab tests alone. The amount we lower the dose is sometimes referred to as an uncertainty factor, or a safety factor. Depending on the amount of laboratory data we have these factors can range from 10-1000. This rather straightforward process helps public health professionals make recommendations about how much exposure people can have, every day, for a lifetime, without being harmed. These exposure levels go by names like Acceptable Daily Intakes (ADI) or Reference Dose (RFD).
Let’s look at an example. If the best available animal data indicates that 10 milligrams per kilogram of body weight per day is a safe dose, to determine a safe dose for humans we lower that number by 10-1000 times (again, depending on how complete the data are). In this example, 10 milligrams per kilogram per day would translate to between 1 mg and 10 micrograms per kg body weight per day as the dose that is safe for humans exposed every day for a lifetime.
Safe Levels for Chemicals That Can Cause Cancer
In the example above, the safe level was based on a dose below which there was no harm from a lifetime of daily exposure—the threshold. When we evaluate risk from exposure to a cancer-causing chemical, we make an assumption that there is no threshold and the chance of getting cancer just gets less and less the lower the exposure (Note: There is an active and ongoing debate about this approach. If you want to know more, reach out to us and we’ll try to help). In this situation, the “acceptable risk” is judged against the chance of increasing the amount of cancer in the population above an arbitrary level set by health policy decision makers. The most common acceptable cancer risk levels used around the world are 1 in 100,000 or 1 in a million. In other words, the safe level is the level that people can be exposed to for a lifetime and only have a 1 in 100,000, or a one in 1,000,000 chance of getting cancer from that chemical and that exposure. It’s important to realize that this approach emphasizes an abundance of caution for deciding how much is safe. It would be very difficult to conduct a health surveillance study and detect a cancer increase of 1 in 100,000 people. For perspective, this would be an incidence of 0.001%. The current annual incidence of cancer (for all types from all causes) in the US is about 400 per 100,000 people, or about 0.4%. Over a lifetime, the risk of getting cancer in the U.S. populations is about 40 out of 100 (40%).
Safe Dose vs. Safe Level in Air, Food, or Water
Our exposure, and hence our dose, comes from air, food, and or water. To establish how much is safe in water, food, or air, toxicologists will take into account how much water a typical person drinks, how much food they consume, or how much air they breathe. For example, we assume that the average adult drinks 2 liters of water per day and the average child drinks 1 liter per day (1 liter is a little over a quart). So, once we establish the safe amount a person can be exposed to per day we simply do a calculation to set the safe level in water at the amount that would be in 2 liters of water (for adults). The same is done for food and air.
The Bottom Line
How toxicologists determine how much of a hazardous chemical we can be exposed to without causing harm is pretty straightforward and can be done for any chemical for which we have appropriate dose-response information. So, when you see terms like Acceptable Daily Intake (ADI) and Reference Dose (RfD), you now know the basics of how those safe levels were determined. We should also point out that these levels can and do change. Like all other fields in science, when new or better data become available, experts make adjustments up or down accordingly.
Dose-Response Curve Showing a Threshold:
Dose-Response Curve for Carcinogens:
