Introduction to Toxicology

Now we move onto toxicology, which looks more at the adverse effects of not just drugs, but all kinds of substances.

1) Demonstrate an introductory knowledge of the scope and history of the discipline of toxicology.

Oh joy, the history stuff. Now I'm not a history buff, so I'm just going to give the bare bones here.

There's been some interest in toxic substances for a long time, which is why the ancient Greeks were able to poison Socrates. (After all, they wouldn't have been able to poison him without knowing what substances were poisonous.) The ancient Egyptians also had recipes for poisons. There was also some guy called Mithridates VI who lived in Pontus (which according to my quick Google search was located in what is now northeastern Turkey). This Mithridates VI chap wasn't one you'd want to cross, because apparently he would test poisons and antidotes on prisoners. (Somehow, I don't think that would pass an ethics board today.)

Moving over a millennium later to the year 1490, in Basel, Switzerland, the medieval physician Paracelsus suggested a very important concept. He suggested that "the dose makes the poison," a phrase that you might have heard before. Basically it means that everything is poisonous to some degree but it is the amount that largely determines toxicity. For example even water can become toxic if you consume too much of it.

Another important figure was Mathieu JB Orfila, the Spanish "Founder of Modern Toxicology" hailing from the year 1787. He made quite a few contributions, including publishing a "Treatise of General Toxicology" when he was only 26 years old. He refined methods for detecting poisons in the body, which was helpful in forensics as well.

Skipping forward to today, the thalidomide disaster of the 1960s spurred renewed interest in toxicology. There are now journals and societies dedicated to it. The end. (Or not, because toxicology, just like any other discipline, is still developing. But writing "the end" gives me satisfaction because I'm pretty shallow.)

2) Show an awareness of the unique opportunities for exposure to chemical substances in our modern world.

As I mentioned when I spoke about Paracelsus, pretty much everything is toxic at certain doses. And "everything" actually includes quite a lot of substances given the variety of things we are exposed to in our everyday lives. Aside from industrial chemicals and environmental pollutants, we are also exposed to a variety of household chemicals, drugs, food additives and so on.

3) Display an understanding of the “dose-response relationship” and its foundational importance to toxicology.

The dose-response relationship is literally just relating the dose to the percentage of patients that experience an effect (i.e. a response). It can be plotted on a graph, which are usually sigmoidal (S-shaped): at lower doses there is little to no effect, but as the dose enters the therapeutic range, the response increases quite steadily until the therapeutic range is exceeded, at which point the graph flattens out again.

Similar curves can be drawn for the toxicity of drugs. At low concentrations, there is little to no effect. The suggested dose at which an effect begins to occur is the "threshold." After the threshold dose, the toxicity increases steadily until pretty much everyone has succumbed to the toxic effects, at which point the graph flattens out again. Patients who respond at lower doses are considered to be "susceptible individuals," whereas patients who don't respond until very high doses are considered to be "non-susceptible individuals."

There are different kinds of susceptibility to drugs. Some responses, the "hypersensitivity responses," basically encompass things such as allergic reactions to drugs. These often require prior priming of the immune system. The other category of susceptibility, "idiosyncratic responses," are generally thought to arise from genetic traits.

4) Demonstrate understanding of the importance of exposure route, exposure frequency/duration, and toxic latency as determinants of toxic effects to foreign chemicals.

Exposure route- Sometimes the route of exposure influences the magnitude of the toxic response. For example, IV drugs can be more toxic than oral drugs. This is because while IV drugs are administered directly into the systemic circulation, oral drugs have to bypass the gut wall and the liver. Inhaled toxicants are also of great concern because it is harder to control your exposure (for example, being stuck in a cloud of secondhand smoke while waiting for the bus).

Exposure frequency/duration- The frequency and duration of exposure can also influence the toxic effects. Exposure duration can be roughly categorised into four categories: acute (< 24hr), subacute (1-30 days), subchronic (1-3 months) and chronic (3+ months). An example in which the toxic effects may vary according to the duration of exposure is benzene. Under acute conditions, benzene causes depression of the central nervous system. However, chronic exposure can lead to bone marrow toxicity and leukaemia.

A related point is that sometimes a drug may be less toxic if administered in smaller doses over a longer time (a process known as "dose fractionation"), but carcinogens and other kinds of mutagens may be exceptions to this rule.

Latency- Latency is essentially how long it takes for a toxic response to appear. Some toxicants show their toxic effects immediately, while others take weeks or even generations to appear.