The Toxicity Problem, Part 2: Shaken, not stirred

This has been a long time coming, but I’m finally updating my three-part series on the bare bones of toxicity testing. My aim with these articles is to provide an easy to understand introduction to chemical toxicity, so that when you hear the phrase “toxic chemical” you’ll be able to understand or question what that means.

In part 1, we looked at how the word ‘toxic’ is only useful when it is in context. In other words, because chemicals interact with different life forms in different ways, what’s toxic to a rabbit might be harmless for a snail (and so on for every different life form!). In this part, we’ll have a look at mixtures of chemicals and how they can combine in unpredictable ways.

A swirling mixture looking sinister...

For starters, most chemicals are tested for toxicity using a dose-response type model. In such tests, an organism is exposed to a chemical in a particular way, and the organism is monitored for a particular physiological response (the simplest is whether or not it dies!). Simple testing of controlled chemical mixtures shows three basic ways in which potentially toxic compounds can work together.

The most straightforward of these interactions is an additive effect – in other words, if you’re exposed to two toxic chemicals, you suffer from the sum of their usual individual effects. This is common when the chemicals have different modes of action; they might target different parts of the body or attack different cell processes, so they each exert their effect independently.

Sometimes, chemicals compete with or inhibit each other’s reactions, which could result in antagonistic toxic effects. This is usually the case when two chemicals have similar toxic effects and block each other’s action. For example, if you have one toxicant blocking the start of the sugar breakdown system cells use to generate energy, another toxicant which attacks the system near the end of its function is redundant.

The third type of interaction is synergistic. This is when two chemicals create a more toxic effect than the two would have if they were present separately (greater than additive effect). It’s synergistic effects which have the most important health implications, for people and the environment, because they are hard to predict or measure. We tend to test either single compounds and mixtures for safety (and that is tricky enough, as I explained in part 1). It simply isn’t possible to predict and test every possible combination of chemicals which will be found in the environment – especially when you consider that a mixture between two compounds might act differently if a third compound was added, or a fourth!

There have been attempts to use models of molecular structure and shape to predict toxicity, with some success. However, these models are generally limited to a particular class of related compounds, and there’s no silver bullet we can apply to all chemicals (and likely never will be). Major synergistic interactions aren’t common in tests of basic toxicant mixtures, but it is likely that there are at least some which have human health implications.

This leads to a concept of a ‘chemical environment’: in the same way that we behave differently in different settings, a chemical’s action and importance will vary depending on where it is and what else is there with it. A highly toxic substance that can’t get past a cell’s outer membrane won’t cause much damage, but if another chemical appears that damages the membrane, it could be a recipe for disaster for the cell.

So, the plot thickens: not only are toxic effects dependent on the type of organism in question, they also depend on the chemical environment, or the particular mixture of chemicals present at a specific place. In the next instalment, we’ll have a look at the big picture; the pathways potentially toxic chemicals can follow in the environment, along with how this can affect their environmental impact. Stay tuned, the next chapter won’t be far off!

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Categories: Science | Tags: , | 5 Comments

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5 thoughts on “The Toxicity Problem, Part 2: Shaken, not stirred

  1. Sorry I missed episode 1. If you’ve already mentioned it then great, but from a ‘health’ perspective, the toxicity can also depend on the ‘health’ of the individual or dare I say it ecosystem (can they have health?).

    I think healthier individuals are more resistant to some ‘toxic’ agents than unhealthy people. I haven’t properly tested that hypothesis yet, it’s just an observation of the ‘slobs’ and ‘non-slobs’ I know.

    If that’s true then, there’s another dimension of assessing toxicity, especially when providing information to people, as some people are proactive about their health.

    Averages don’t necessarily apply to individuals.

    • Good point. I didn’t mention that, and it’s important in debates such as for fluoridation of water.

      I think I need to make my link text stand out more – part 1 is linked (start of second paragraph), but it’s almost impossible to see!

  2. Pingback: Phew « David Robertson

  3. Hi,

    actually, “additivity” in the area of mixture toxicology refers more often to “concentration additivity”, which is something rather different that the simply arithmetic sum of effects. And usually Concentration Addition is contrasted with Independent Action (also called Response Addition), but if that is slightly different from summing up effects. E.g. if you have two compounds, each provoking 50%, you would not expect 100% effect from the combination, but only 75%. The thought experiment goes as follows: first compound kills 50%, and the second one also kills 50% – but only from those that survived the first compound. The total effect is then 50% plus 50% of the remaing 50% = 75%.

    • Thanks for the clarification – you’re right. My definition was a simplification of the two (different) forms of additive effects, and straightforward summing will give a different type of answer to calculating an expected value from proportional increases in toxicity with multiple compounds. I’m a bit annoyed I made that mistake actually, it’s similar to the ‘racecar on a train’ vector addition problem in physics!

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