How are permissible exposure limits determined if you of course can’t test dangerous substances on people?

Question

I am doing some research on the toxicity of a particular ‘mildly neurotoxic’ gas and I can’t quite find how the permissible exposure limit is determined. I can find research on acute exposure LC50’s in mice and rats, but an acute LC50 is of course very different from the concentration at which irreversible health effects start to occur after years of exposure.

Obviously you can’t place a number of humans in a room with a substance for several years and see what happens, which led me to wonder how these limits are set.

In: Biology

Answer 1

We use a combination of animal testing and predictions based on biology and chemistry. When we have case reports based on real-world exposure, we can use those to help make better estimates. An agency that sets guidelines for safe working condiitions will have scientists review the data and make recommendations to be put into law.

If we see that a toxin has a certain effect in rats, we can use what’s called *allometric scaling* to estimate how much of that toxin would have the same effect on a human. This is the same calculation we do when developing new medicines. It’s based on several things. One is metabolism: rats are similar to humans in how they process toxins and drugs, but they handle some things differently than we do. Another very important one is body size, which is mostly based on weight, but also accounts for things like the ratio of surface area to volume, which is much higher for a smaller animal.

If we know that a toxin causes damage to certain types of cells or proteins, or we know how long it takes to clear out of the body, we can calculate how much exposure over time (“area under the curve”) will cause damage that the body can’t fix. For example, lead behaves sort of like calcium in a lot of chemical reactions, so it interferes with certain functions that depend on actual calcium to work right, like keeping nerve cells healthy. And it takes a very long time to clear out, so we really want to limit a person’s lead exposure so that it doesn’t build up too much over time and cause nerve damage.