Toxicology: the poison and the dose

Equally as interesting as pharmacology, toxicology is a closely related field that studies deleterious effects of chemical compounds applied to the body. We hear a lot of generic use of the word "toxins" out and about in the world today, but what exactly is this supposed to mean anyway?

Toxicology of a given compound is determined by three main factors: what is the physiologic action of the compound, how potent is it, and what dose is being applied? Let's take a closer look at each of the factors and what they mean.

What's it do?

That's the first thing I think when I hear someone say something is a toxin. There is no single "toxic" reaction out there. Every toxicologically active chemical entity out there has its own mechanism, its own target. Some are more recoverable than others, some have pretty dire consequences; some we have antidotes for, some not. Some exert an effect quickly, while others can take their time. They can target any physiological system, or multiples.  Cause death, permanent injury, reversible injury, minimal harm, or anywhere in the middle. Locally, regionally, systemically. There are many, many examples of different actions that a given compound could do. The severity of the effects is important to evaluate.

How potent is it?

Potency is critical in toxicology. The more potent a compound is, the less of it is required to cause an effect. So if something is extremely potent, we're gonna be worried about it and carefully scrutinize any exposure level. On the other side of the spectrum, if it's not at all potent, the likelihood that a common encounter will result in severe effects is very low. This is a major consideration when thinking about how harmful a given exposure could be. If it takes literally bathing in something to cause any harm, well, it's less to worry about than a potent snake venom toxin where less than a milligram could knock you dead. This determines the amount of caution with which we approach a given compound.

Figure 1. Potency concept. (x axis should be more appropriately labeled drug dose.) High potency drugs cause effects at a much lower doses than low potency drugs. In the context of toxicology, this means that a low-level exposure is of much greater concern if the compound is of higher potency.

What's the dose?

This matters mainly because the potency factor matters. I list it separately because dose is a related but distinct factor, and also because putting vastly excessive amounts of many things into the body can cause physiological damage.

Like therapeutic effects, one can generally observe a dose-response effect when examining toxic effects of a given compound. Like so:

Figure 2. Increasing toxic effects observed as a factor of increasing dose.

In this imaginary case (as in most real cases) some doses are so low that there simply is not enough of the imaginary compound in the body to cause any effect at all. LOAEL is the lowest observable adverse effect level, or the lowest dose that reveals any adverse effects at all. Beyond that level, things start to get more detrimental. What dose someone actually gets exposed to is a major factor in the level of toxic effects might happen as a result.

Of course, exposing oneself to exaggeratedly too much of anything can be harmful. A popular example is water, since it seems pretty harmless. Drinking stupidly excessive amounts of water can screw up the body's salt balance, causing hyponatremia and possibly death. So it's not too far out there to say that going ridiculously way-out-there overboard with just about anything has the potential to cause harm.

Therapeutic index

A final note- this is a pharmacology blog, after all. Yes, there are plenty of drugs out there that have toxic effects at some dose or another. Since we typically look at/discuss therapeutic effects, it is worth mentioning that this toxicological dose-response is also considered in the process of drug development. The difference between the dose-response for therapeutic vs toxic effects is generally called the therapeutic index. Something with a very narrow space between therapeutic effect and toxic effect is said to have a very narrow therapeutic index, while something with a pretty nice distance between the two curves has a pretty favorable therapeutic index.

Figure 3: TI, or therapeutic index. The therapeutic effects (open circles) and the toxic effects (closed circles) are compared, and the difference between the curves is used to determine the therapeutic index. This imaginary example is definitely not an ideal TI, since the therapeutic and toxic effects have substantial overlap. The more space between the curves, the better.

The TI is an important consideration when looking at dosing regimens. If accidentally taking a dose twice (or slipping up on dose timing, which is something that just happens from time to time) would bump up the circulating drug levels enough to put someone on the toxic effects curve, that's something that should be avoided as much as possible by adjusting dosing regimens- or considering alternatives with more favorable TIs.

In summary

Think about this next time you run across the broad-brush phrase including how terrible "toxins" can be. What toxins is the broad-brusher referring to? What do they do? How potent are they, and how much of these toxins are we exposed to? We live in a world full of chemicals, and we're exposed to damn near everything at some level or another. Some of these do hold potential for harm. Some do, but not at levels that we're exposed to. But I suspect you'll find that asking specifics about the broad-brush "toxins" phrasing commonly used will get you some hand-waving or stunned silence. Empower yourself with understanding. Toxicology is fascinating stuff, and definitely not something to be hand-waving over.