Poisons, or what it takes to get the skull and crossbones
A poison is a biologically active chemical substance, such that when it ends up inside the organism in small quantities, it causes grave, permanent damage to a definite degree. It is crucially important that every part of this definition must be fulfilled. Otherwise the substance is not, at least technically, a poison. A poison need not to be lethal, but the illness it causes must become irreversible at some dose. In general, the official "poison" label is given to relatively few substances in order to not to cause inflation of the value of the label.
Official labels are given by the International Labour Organization (ILO), in its International Chemical Safety Cards (ICSCs). A new system called Global Harmonized System (GHS) is being introduced, and it supersedes American and European criteria and the old national labels (i.e. EU's orange labels and NFPA diamonds). In the European Union, uniform standards have been enforced. In the United States, labelling has been unsystematic and several substances with other hazards, e.g. hydrochloric acid, have been labelled "poison". This is due to change with the introduction of the GHS.
Poisons are not mystical. Most frequently this issue comes up with radioactive poisons (plutonium), commonly known poisons (strychnine) and extremely carcinogenic substances (any aromatic). Poisons are commonly mixed up with harmful and corrosive substances. So, let's make it a bit more clear!
What is and isn't a poison
First of all, a true poison must be toxic in small quantities. In common usage this requirement is not taken into account and so too many things end up with the label "poison". For example, drain cleaner is not a poison. Drinking a small quantity of it causes local burns in the mouth and below, but ultimately stomach acids neutralize the base. Also, the taste and its effect gives an effective warning against drinking it. Drain cleaner becomes lethal or permanently destroys parts of the stomach only if a substantial amount of it is drank. A harmful substance can be called a poison if a small quantity can be lethal or gravely damaging. For example, cyanide is a poison: Alan Turing killed himself by eating an apple dipped into cyanide. You can't contaminate a food with drain cleaner and render it lethal to eat. Maybe nasty and corrosive, but not really lethal.
The second thing about the poison is that it must actually be a poison, not just playing one on TV. For example, ethanol is a depressant drug, not a poison, even if people end up causing their own death (or somebody else's, for that matter) when drinking it. Another nonpoison is potassium chloride, the substance used in executions. Eating a substantial amount of KCl can cause death, but that is called nutrient overdose, not poisoning. In order for KCl to kill effectively it must be injected, which doesn't happen by accident. KCl causes a heart attack by imbalancing the ion concentrations of nerve cells, but otherwise, no damage is done and the salt is safely excreted in urine. (Lethal dose is about 2 tablespoons minimum1, or the LD50 is 2600 mg/kg orally.2)
Then there are many so-called "poisons" which are not hazardous substances at all. Sugar (pure glucose, fructose, saccharose) is one. Though it might be true that sugar is counterproductive it doesn't make it a poison. Another example is fried or baked food. Although heating and especially charring does produce small amounts of highly carcinogenic substances, that doesn't mean that bread has to be labeled poison.
It can be argued that nuts and apple pips are poison to those who are allergic to them, but in general, a possibility of an life-threatening allergic reaction doesn't make a substance a poison. Similarly, harmful, irritating and carcinogenous substances aren't automatically poisons. A harmful substance is likely to cause damage, but not grave and permanent or lethal, in small amounts. An mere irritant might be harmful in large and lethal in larger amounts, but in its expected usage, it causes only irritation. Examples include bleach and turpentine, which are not expected to be drank. There are numerous cases of dementia sufferers who have drank bleach and died. However, they have done so deliberately, because the taste of bleach gives a clear indication it's not potable. (In fact, some American health supplements to combat "excess acidity" are nothing but bleach: nothing more, nothing less.)
Another class of probable non-poisons are the corrosive substances. Few of these are actually poisons, though in the non-EU they might be labeled as such. Their danger lies in the simple tissue damage they cause, not in their inherit toxicity. There, however, are corrosives that are also poisons, for example hydrofluoric acid, which contains poisonous fluoride ions2. (Yes, the same as in toothpaste. It's a dangerous life!)
Toxicity itself doesn't make a "poison" either - it's the danger which does. Obviously more toxic substances are more likely to be dangerous. However, in the new Globally Harmonized System, there is a new classification for acute oral toxicity, which has three categories of poison:
- Category 1 (with the warning "fatal if swallowed") has a LD less than 5 mg/kg
- Category 2 has 5-50 mg/kg ("fatal if swallowed")
- Category 3 has 50-300 mg/kg ("toxic if swallowed").
- With a LD50 of 300-2000 mg/kg, the substance is in category 4 ("harmful if swallowed") and the hazard pictogram used features an exclamation mark, not skull and crossbones. These substances are not true "poisons", but only "harmful".
- The even less dangerous category 5 has no required hazard pictogram and the warning "may be harmful if swallowed". These substances are not "poisons", but "harmful".
Carcinogens, mutagens and teratogens, sensitizers, and substances with insidious toxic effects (on specific target organs) have been labelled with textual warnings and with a "poison" pictogram (skull & crossbones) if applicable. In the GHS, a new pictogram is introduced.
Characteristics of a poison
A poison might get into the body by ingestion, inhalation or absorption through the skin, and what it does there is absorption. This differentiates it from corrosives, irritants and others: a corrosive doesn't specifically absorb into the bloodstream or other system. A corrosive just destroys tissue, it doesn't incapacitate any chemical system in the body. Neutralizing the corrosive effect stops the symptoms, but for a poison, that alone doesn't help.
Also, to get a poisoning, the poison must be actually enter the body: via skin or eyes, mouth or the lungs and other respiratory organs. This applies to radioactive poisons, too. Only very strong radiation can enter directly without a carrier. In the event of a major nuclear disaster it is relatively easy to prevent poisoning, because the fallout is dust, which can be avoided as easily as average dirt. (Or, it's just as difficult.)
A poison is characterised by a poisoning, or the illness it causes. This is crucial. If a patient has a poisoning, no amount of forced vomiting helps the poisoning itself. It may stop absorption of yet unabsorbed poison, but will not do anything else. Absorbed poison is what counts for a poison - the corrosive in contact with the skin is what counts for a corrosive. After the absorption, only detoxification can help. Similarly, if you already have the traveller's diarrhea, washing hands won't help you anymore: you've already eaten the pathogen.
Another property that characterises a poison is its dose: detectable, harmful, and lethal dose. In this respect, radioactive poisons are the worst sources of confusion. A human body is, fundamentally, a 70-kg bag of small phospholipid bubbles in which different reactions occur and which are very effectively buffered and constantly detoxified. To kill or damage a human, the concentration of the poison must be large enough. An infinitely small amount of the worst possible poison will have no effect, because affecting one molecule of 70 kg of stuff will not do anything significant. (Remember, simple carcinogenicity - from DNA damage - doesn't automatically qualify a poison.)
There are substances that are both poisonous and corrosive. Hydrofluoric acid is one: it not only acts as an acid, but contains poisonous and quickly absorbed fluoride ions. Hydrochloric acid, on the other hand, is only corrosive, because neutralizing HCl stops the damage. The chloride ion is not poisonous.
The mystic radioactivity
So, there's a lot of mystery about the Chernobyl disaster, where a substantial amount of radioactive poisons was released into the atmosphere. Here are some facts3: other than the immediately affected (134) the only definite increase in cancer was in thyroid cancer. 1800 cases were found. Some cancerous growth in the thyroid is found, varying by region, in 6-20% of all autopsies, and 2.7% of people carry thyroid cancer unknowingly (or not)4. Thyroid cancer has a low mortality rate: in the region, 10 out of 1800 have died, which corresponds to a 0.6% rate. The chances of getting it decrease with age to essentially zero at the age of 15. Other effects have not been found. The toxicity could be then called "weakly carcinogenic" at most.
The problem here is that being radioactive automatically makes a poison a mystic entity, which is like the virus in anti-virus marketing. Thus, I must object to the notion that a plane crashing to a nuclear power plant would be exceedingly dangerous; it's not safe, but it'd be definetely manageable and cause little effects. See nuclear power.
Worse yet, concentrating on radioactivity alone leads to ignoring the traditional chemical toxicity of radioactive metals. You can't write off the dangers of radioactive metals just by looking at the Geiger counter. Plutonium and uranium, for example, are toxic heavy metals, and their chemical toxicity is more dangerous than their radioactivity. Other toxic heavy metals are lead, mercury and chromium.
What poisons are
Why substances are poisonous, then? The simple answer is that they, or their metabolites block, damage, misdirect or oversaturate some chemical pathway that is essential for life. There are a myriad of pathways to be blocked.
Some actual non-poisons also metabolise in the body into poisons: for example, benzene, other aromatics and aflatoxin are in itself are not very harmful, but the liver makes epoxides out of them to add water and so detoxify them. The method is reasonable, but there's one little problem: the epoxide is quite stable and very damaging to DNA. As they are fat-soluble, they easily traverse cell membranes, to the center of the DNA helix, where they will irreversibly bind to the DNA.
Simple disruption of the electron transport chain, that is, cell respiration, will kill quickly. One famous example are the cyanides. The cyanide ion - which comes from inhaled hydrogen cyanide if mineral cyanide is ingested - changes places with a ferric ion in cytochrome oxidase, and the electron transport is cut: oxygen will no longer receive the electrons it needs to "burn". The poisoning is similar to a heart attack or choking. Again, if small amounts are ingested (such as in prepared cassava root) the effect is very small.
The most common immediately lethal poison in the world is still carbon monoxide, which is given off in incomplete combustion, either from a fireplace or a smoldering fire. Carbon monoxide is a invisible, tasteless, odorless gas that makes the victim sleepy due to hypoxia. The combination of carbon monoxide and haemoglobin is more stable than that of oxygen, so that when inhaled, oxygen transport in the blood is blocked.
A poison can misdirect a system in the body. One of these is hydrogen sulfide in large concentrations1. First of all, it is a respiratory inhibitor like cyanide. However, it first desensitises the nose, then causes some lack of oxygen, which results in rapid breathing. The heightened concentration in the blood paralyses the respiratory centre in the brain. Respiratory paralysis follows. These poisonings are rather common in contexts where decomposing matter has been stored for a long time in a confined space, e.g. in septic tanks. The smell is a good indicator, but desensitisation is fast and thorough. However, if the breathing apparatus is not affected, and there are no other effects, there's no reason to fear the poison. We the chemists breath in H2S constantly for the first autumn in the qualitative analysis labs, and it just smells bad.
Catalytic poisons are antagonists to an essential catalyst. Metals (as such) are of this type. The term "poisoning" also applies to completely inanimate inorganic catalyst incapacitations such as poisoning of the car's catalysator by leaded gas, not only to living things. A enzyme is a protein-based catalyst that catalyses a certain reaction, which may be essential to life. These may need a metal ion or a vitamin molecule to work; if the wrong metal ion is bound to the enzyme, either as in the place of the vitamin or the product, the enzyme is incapacitated and will not work anymore.
Skinwalker adds: "The most effective poisons are probably catalytic... look at ricin, for example. One ricin molecule can destroy an entire cell by binding a ribosome, cleaving a specific chunk of RNA, and then moving on to the next ribosome." This leads to the death of the one cell. But, on the other hand, there are billions of cells in the human body, and none are vital alone.
Metal poisons are permanently harmful if they accumulate. Mercury is one such. The folklore of the mad hatter is based on the accumulation of mercury from the paint that was used to felt the hats. The hatters got permanent brain damage from being exposed to the mercury fumes.
The definition of a poison includes that it causes permanent damage, but some are lethal because they cause irreversible, terminal damage. The most known is paracetamol, the effective ingredient in Panadol and other anti-inflammation painkillers. One, rather ineffective (<5%) route leads to a poison NAPQI, which is metabolised by glutathione. Each molecule of NAPQI uses a molecule of glutathione, so if an overdose is taken, NAPQI wins and causes terminal liver damage. And that's what we eat when there's a headache.
Nerve gases, in particular, overexcite a healthy system. For example, VX causes buildup of the neurotransmitter acetylcholine, which leads to stiffening of every muscle, which overpowers the respiration system and kills the victim. The toxicity of large doses of dextromethorphane is the brain cell analogue of the same effect: brain cells cease to rest and sustain an excited state until they die. This is called excitotoxicity. The victim is left with little holes in the brain called Olney's lesions. In normal doses, DXM is a cough medicine and a potential hallucinative drug, but at more than 2-4 g, there's little chance of coming back. Popular formulas are laced with laxatives, so the "poison" label isn't applicable. If it was a cleaning agent, it'd definitely have the skull and crossbones.
Conclusion
The conclusion is that a poison claim must always be fully evaluated:
- A substance called poison might be a mere irritant.
- There must be route for the poison to actually enter the body. Action at a distance applies only to very strong radiation.
- There are no infinitely poisonous substances. The poison must either attack a very specific site or if it's nonspecific, destroy the lungs in order to kill. A limited amount of nonspecific or reversible tissue damage is only harmful.
- Poisons have definite limits at which they are poisonous and at which they become lethal. Below them, the effects are reversible and/or neglible.
- The effect of a poison will be limited by its dose.
Let us see the effects and actual LD50's of various poisons and non-poisons and their international classifications (from the ICSC). Tested on rats with oral doses unless otherwise mentioned. Notice two things: LD50 doesn't correlate with the toxicity rating: the rating is a measure of potential damage, not per-weight toxicity. Some orientation: 100 mg is about 2-3 microspoonfuls, or needlepins' volume of organic crystals, so a 80 mg dose (lethal for <50 kg) of warfarin is about two needlepins, which is little, but not invisible.
Warfarin 1.6 mg/kg, toxic T. Anticoagulant rat poison.
Strychnine 2.350 mg/kg, very toxic T+.
Potassium cyanide 5 mg/kg, very toxic T+. Respiratory inhibition.
White arsenic As2O3 14.6 mg/kg, very toxic T+.
Nicotine 50 mg/kg (rabbit), very toxic T+. Insecticide.
Caffeine 192 mg/kg, harmful Xn. Heart arrhytmia.
Napthalene 490 mg/kg, harmful Xn. Carcinogenic.
Ethanoic acid 1060 mg/kg, (corrosive C). A.k.a. vinegar. Corrosive.
Carbon disulfide 3188 mg/kg, toxic T.
Methanol 5628 mg/kg, toxic T. Blindness etc. from metabolites.
Sodium hypochlorite 8910 mg/kg, irritant Xi. Oxidiser.
Gasoline 13600 mg/kg, toxic T. Lung damage, carcinogenic.
Soot 15400 mg/kg, no hazard rating. Particulate.
Some poisonous nodes: cyanide, Zyklon B, Don't mix acetaminophen with alcohol, VX, most toxic plant poison, most toxic fungal poison, LD50, nerve agent, deadly nightshade.
Sources:
- Hazardous Substances Data Bank
- WHO, Internation Chemical Safety Cards
- Säteilyturvakeskus (stuk.fi)
- The Thyroid and Its Diseases, Chapter 18, Thyroid Cancer. http://www.thyroidmanager.org/Chapter18/18-Incidence.htm
Respectable Peer Reviewers:
- True wisdom trickled down by the honored Doctor in this field, Professor Pi.
- Editorially inspected by mkb.
- Skinwalker's point: enzymes may require a metal ion.