To Add or Not to Add?

How much is one and one?

In math, or apples, or oranges, it's always two.

But not if it's apples and oranges.

And not if it's in toxicology—the study of chemicals’ potential effects on living organisms. Sometimes, it's two. But more often, it's not.

Take the case of chemicals that enter our bodies from the environment, which some refer to as our "body burden." Scientists at the Centers for Disease Control and Prevention (CDC) are doing important work measuring the amounts of chemicals that get into our bodies from eating, drinking, inhaling or touching (see Biomonitoring in this section). The CDC looked for 116 natural and man-made chemicals and found evidence that most of them are in most of us at one time or another. The majority are present only in trace amounts and, in all but a few cases, are quickly broken down and excreted. But some are asking, couldn't a little bit of this and a little bit of that perhaps add up to trouble?

The question is well worth asking. As any pharmacist will tell you, some drugs enhance the effects of other drugs, or diminish the effects or completely negate them the way an antidote counteracts a poison. In thinking about the various trace chemicals around us, we wonder whether there are unforeseen consequences of exposure to these chemicals in combination—what some call "aggregate exposure."

Pharmaceutical agents are taken in doses large enough to produce the desired effects. But what about trace chemicals, which enter our bodies at levels far below those that produce effects in laboratory animals? Do chemicals at these levels interact with each other, and if they did, what would be the consequences? We know that some chemicals can interact, although it appears that many may not. For some chemicals that can interact, they do not seem to cause significant adverse effects as long as the exposures are very low.

The evidence indicates that for the few chemicals that we know do interact, most do so by a process called "additivity," in which the effects of these chemicals are added together. But in order to be "additive," chemicals must produce their effects not only on the same organ systems, but in the same way. In a toxicologist's terms, their "mechanism of action" in the body has to be the same for the effects to be additive. Another important point relates to the exposure levels. To produce meaningful interactions, exposures must be at levels at which the respective chemicals produce effects. If the exposures are below a critical threshold, an "additive" effect would not generally be expected.

Is it possible to know in advance whether certain types of chemicals are likely to interact? In some cases, scientists can accurately predict the processes by which chemicals produce effects by comparing molecular shapes, or by comparing existing data on various compounds in the same family. If there is doubt, and the exposure is significant, the doubts can be resolved by testing. This is where the CDC biomonitoring data may be very helpful. They can reveal where similar-acting chemicals are detected at levels at which their combination might—or might not—be of concern.