We live in an era where our bodies can encounter far more toxins - of various types - that it could have back in the ancient days.
When encountering some new toxin that the body’s never seen before - let’s say, the first time someone inhales methylene chloride, or ingests aflatoxin, or some heavy metals - how do your organs recognize “This substance is bad for the body, and we need to excrete it?” Or even when the 10th or 50th time, how would it know? It’s not like white blood cells, where your body knows to eat germs in the bloodstream, or virus antibodies.
How does the body “know” which substances, like lead or mercury, need to go, and which are harmless and should stay?
Well… sometimes it doesn’t know and the Bad Stuff stays in your body. Like when your body mistakes radium for calcium and uses it in, say, your jawbone where it kills surrounding tissue which you body then tries to repair with more calcium but oops! that atom was actually radium… rinse and repeat until your jaw literally falls out of your head.
But in other instances the substance has some similarity to things your body already knows are bad news. Sometimes the body can eliminate these things with mechanisms it already has. Sometimes it can’t do that very well - your body does excrete lead, but does not do so quickly. Sometimes it can wall off something foreign, creating a cyst, or encapsulating it in scar tissue, or sometimes it “works its way out” of the body, emerging from the skin (that happens with shrapnel sometimes). Sometimes the liver can detoxify or neutralize a poison, or modify it so the kidneys can better excrete it.
Over time we can evolve to have better mechanisms for dealing with a toxins we encounter often. There are clusters of people who have lived a long time in areas where the water naturally contains more arsenic than average who have evolved the ability to better excrete from the body, as an example.
So… the means vary, as does the efficiency in dealing with the problem.
The liver is the first stop for stuff absorbed through the stomach. It’s designed to shred most larger molecules down into component parts. So although the liver has no specific idea what to do with some some novel chemical invented in a lab last week, it does know that chopping everything into small fragments is its daily job.
Now the liver has a finite repertoire of moves it can make to tear apart amines or shred phenols or whatever. So some stuff leaks through. Even completely natural stuff that predates the existence of life on Earth. For example there’s next to nothing a liver can do to elemental lead or mercury.
One of the difficult jobs for medicinal chemists is to figure out how to slip their latest miracle drug compound past a liver that desperately wants to convert it into simple sugars and some loose oxygen and nitrogen. By that time the “pill” is just a cloud of loose molecules floating in blood, so clever pill packaging, buffering, etc., is already moot. That stuff way well have helped get your molecule past the stomach acids and mucous membranes and whatnot into the portal blood enroute to the liver. But that’s of no use now versus the liver’s chemical slaughterhouse.
I’m also not sure that we encounter fewer toxins today than in the past. Nature is full of things toxic to humans. Anyone who has taken courses in outdoor survival learns of many chemical dangers you encounter in nature.
We needed to develop some mechanisms to cope with such things (all animals do to an extent). I remember asking once on this board about why it’s common to vomit when you get dizzy, and someone wise advised me that a common symptom of being poisoned is dizziness, so the body’s automatic reaction is to try to remove whatever you ingested. It doesn’t know if you are dizzy because you ate poisoned berries or because you just got off the teacup ride at Disney Land.
So at least in cases of acute toxicity, the body has ways to react to symptoms without recognizing the nature of that toxicity.
It actually sort of does. Back in the olden days, various forms of mercury were used as a laxative, due to the body’s efforts to expel it, if they kept it down long enough. It’s when the mercury enters the body some other way that toxicity is more of a challenge.
And once it gets through the liver (AKA first-pass metabolism, when a drug is taken orally), they may need to figure out how to get it through the blood-brain barrier.
AIUI mercury has a low bio-availability. In short, most of what you consume will just pass through you.
But not all of it and what the body does retain is cumulative. A little here and there is no big deal (e.g. eating fish) but, over time, it adds up and can become a problem because your body does not rid itself of mercury.
Note: There are different kinds of mercury…I am unsure if there is a difference as far as our bodies are concerned.
The salt or ester definitely alters the way mercury, and other heavy metals, are absorbed and excreted, as this chemistry professor found out the hard way.
Which swiftly gets us to a big fraction of drug interactions. The liver has a finite ability to degrade stuff, and if the degradation pathway is already working hard to break down drug X, adding drug Y that also has the same degradation pathway to the mix can result in both drugs rising in concentration.
Lots of drugs are processed by the family of Cytochrome P-450 heamproteins. These are not just in the liver.
A famous example of interaction is how grapefruit juice interferes with a P450 pathway in the small intestine resulting in higher than intended doses of a drug making it into the bloodstream.
Monoamine oxidase inhibitors are another great example of stuff that goes wrong. Monoamine oxidase degrades another class of stuff we eat, but also plays a part in regulation of neurotransmitters, degrading them at a constant-ish rate leading to a stable concentration. Treating depression with inhibitors of MAO increases levels of the transmitters, which can be beneficial, but reduces the amount in the gut that is making stuff safe to eat. So foods with lots of monoamines get past - with potentially life threatening results.
The body is fairly good (not perfect) at recognizing what we are evolved to keep.
Everything else it tries to get rid of, or not absorb, with varying success. Some things are enough like what want to suck up and keep that we get rid of them poorly. That’s the case for lead: it is similar to calcium and iron and kids in particular are needing to suck those things up, lead gets caught up with it.
And of course some things our bodies are really bad at getting rid of … microplastics and very tiny inhaled particles for example.
I remember that specific case. I was an undergrad working in a lab with chemicals to fix and embed tissues in plastic. I wore the standard latex gloves until someone more experienced told me to switch to polyethylene gloves like the ones used for food prep.
Plus the very concept of a “toxin” is nebulous. It’s typically not a binary distinction between good and bad substances. That way lies the madness of some of the modern homeopathic “detox” culture.
As we typically attribute to Paracelsus - the dose makes the poison. Many if not most of the things we actually need to consume on a regular basis (most vitamins, for example) are toxic at high doses and we can’t just not consume those. Like, it’s a good idea to make sure your diet includes a healthy amount of Vitamin A, even if Vitamin A toxicity can be a real thing at very high doses.
Some things we consider bad - formaldehyde, for example - occur naturally at very low levels in many foods and we break it down naturally. But it doesn’t take a lot of formaldehyde to be incredibly bad for us. So, go ahead and eat apples but don’t drink straight formaldehyde.
I would think, stated simply, it is clear our bodies do not know how to rid itself of any toxic substance. Poisons exist. Venom exists. These will make us very sick or dead because our bodies cannot rid itself of these things.
I thought it was that the body DOES know to excrete these things, but unfortunately, they usually kill before the body has enough time to do so. Like snake venom killing you in 1 hour when your body might have been able to excrete it in 24 hours (if given enough living time to do so.)
Basically, It doesn’t. It only knows stuff that should be in the system and stuff that shouldn’t anything that shouldn’t be in the system gets discarded through various methods at our bodies disposal. So when it finds stuff that shouldn’t be in the system, it tries to take them out. For example your tattoos. The ink in the tattoos shouldn’t be in your system, but as the molecules are far too big, the white blood cells basically wrap around it and keep them in place, so that they don’t spred to other areas of your body. It’s as simple as that.
That becomes something of a tautology. We end up defining toxins as things that will kill us. Thus we have ring fenced those compounds we don’t process or eliminate as toxins, and stuff we do process and eliminate as non-toxins. Thus we will never be able to handle toxins, because by definition, they can’t be toxins if we do.
There is a lot we eat that will kill us if we didn’t have existing chemical pathways to manage them.
One example of the problems is the manner in which various compounds are toxic to some animals and harmless to others. Many insect sprays are basically neurotoxins. Not far removed from nerve gasses. They kill insects and not us because we have the ability to break them down fast enough that they don’t kill us.
Theobromine is mostly harmless to us, but is the reason chocolate will kill dogs. We process it much faster and it doesn’t cause us problems (mostly). Rats can manage about the same dose as humans. So it isn’t as if we are special. Binge on a few kilograms of extra dark chocolate and you might sympathise with the dogs that ate the chocolate cake.
We can become “immune” to some toxic agents. We make antivenin for snake and spider venom by harnessing the immune system of horses to make antibodies to the particular cocktails of evilness in the venoms. (Not an exact science, which is part of the reason antivenins really knock people about, and doctors won’t inject you until they are convinced you need it.) We could, in principle, inoculate ourselves to build up a capacity to neutralise venoms. But it is probably not a recommended path to tread, no matter how much one hates crawling or slithering critters.
Actually, on a per-weight basis, theobromine is only a little more dangerous to dogs than to humans. The reason chocolate is bad for dogs is that, first, most dogs are smaller than most humans, and second, dogs will binge on foods in ways that most humans won’t. A 60 pound dog, given the opportunity, might each 10 pounds of chocolate at once, but a 180 pound human wouldn’t eat 30 pounds.