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Lethal Doses of Water, Caffeine and Alcohol

Lethal Doses Chemicals Chemistry
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Today’s graphic is a whimsical look at lethal doses of chemicals we consume on a regular basis. Whilst it may be more common to view chemicals in a black and white framing of ‘toxic’ or ‘non-toxic’, the reality is more of a sliding scale of toxicity. The admission of too much of any chemical into the body can cause toxic effects, and even death – the only variant from chemical to chemical is how much is ‘too much’. For some chemicals, the amount will be very low, whilst for others, it may be almost impossibly high.

So, how can we compare the toxicities of differing chemicals, when they can all produce varying effects, and these effects all require the intake of differing amounts? One of the most commonly quoted figures when discussing the toxicity of chemicals is the LD50, which stands for ‘lethal dose 50%’, or ‘median lethal dose.’ This is the amount of a chemical required to cause death in 50% of the animals in the group it is tested on. The figures can be given for when the chemical is given orally, when it is applied to the skin, or when it is injected into the animal. The results of these tests can then be converted into figures for humans, and expressed in milligrams per kilogram of body weight. The smaller the lethal dose, the more toxic the chemical; thus, the LD50 provides a way of comparing the toxicities of all chemicals.

There are a number of caveats to the LD50 test. Firstly, as mentioned, it is the dose required to kill 50% of the test subjects. Therefore, it does not guarantee death – in fact, it’s possible to take more than the lethal dose and live, and take less of the lethal dose and die. For the purposes of clarification, other types of lethal dose data also exist: the LDLo (Lethal Dose Low) is the lowest dose known to have resulted in fatality in testing, whilst the LD100 (Lethal Dose 100%) is the dose at which 100% of the test subjects are killed.

Another issue with the lethal dose tests is the obvious fact that animals are not humans. The sensitivity of animals to different chemicals varies from species to species, and can also vary from that of humans. A prime example is that of the chemical theobromine, found in chocolate. Humans can stomach around 1000mg/kg of their body weight of theobromine; this is quite a large figure, and means it’s next to impossible for a human to eat enough chocolate to die of theobromine poisoning (an average 200g bar of milk chocolate contains a little under 300mg). Compare this to dogs, who can only tolerate around 300mg/kg of their body weight, and can therefore easily die as a result of eating too much chocolate. Therefore, there’s no guarantee that the figures converted from animal lethal dose tests are always reliable in humans.

Additionally, although lethal dose tests provide absolute figures, these will invariably vary from person to person dependent on a wide range of variables, including physical condition, and medical conditions they may be suffering from. The lethal dose of a compound also tells us little about what dose effects of its toxicity start to be manifested. Some chemicals may have a high lethal dose, but may cause toxic effects at a dose much lower than this.

A final issue with the lethal dose tests is one of ethics. There is obviously an aspect of animal cruelty involved in the tests, and for this reason they are now being widely phased out, with other methods for assessing toxicity preferred. Several alternatives have been developed:

  • Fixed Dose Procedure: In this test, five male and five female rats are used. The chemical being tested is given to them orally at one of four fixed dose levels (5mg, 50mg, 500mg or 2000mg). Rather than trying to identify the dose at which death is the result, instead the test tries to identify the dose at which toxicity can be observed. Testing stops once this is seen. Although this still uses animal subjects, it drastically reduces the number of animals required, as well as the mortality rate.
  • Up and Down Procedure: In this test, animals are tested one at a time, and observed for 1-2 days. If they survive, an increased dose is given to the next animal, whilst if they die, a decreased dose is given. Again, this reduces the number of animals required, but does not completely avoid their use.
  • Acute Toxic Class Method: Still uses animals. A stepwise procedure, where three animals of the same sex per fixed dose level are used. Dependent on the outcome, a decision is made as to whether further testing is necessary.
  • Cell-Based Screening Methods: Involves studying the effects of chemicals on cells removed from their biological environment in the lab. This alternative avoids the use of animals, and scientists hope that in the future, it will be able to be used exclusively.

To conclude, it’s clear that the LD50 method of categorising chemicals, whilst providing a useful comparison, has several flaws. For that reason, it is largely considered to be a somewhat outdated method for determining toxicity. Nonetheless, LD50 figures are still frequently quoted for various chemicals, and it is unlikely that references to them will ever be phased out completely, at least in more general parlance.

As a final note, the graphic provides the LD50 values for water, caffeine and alcohol (ethanol). It’s worth noting that, in the case of caffeine, drinking 118 cups of coffee would almost certainly see you dying of water poisoning before caffeine poisoning! The figure for alcohol is also especially variable, including whether or not you’re drinking on an empty stomach, as well as personal drinking history.

I’m indebted to Justin Brower for the content of this graphic, with whom I corresponded on the figures, who was able to provide some very useful feedback and suggestions. Justin runs the excellent blog ‘Nature’s Poisons‘ which, unsurprisingly, looks at the various poisonous chemical compounds found in nature and is well worth a read.

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58 replies on “Lethal Doses of Water, Caffeine and Alcohol”

“There are now toxic compounds only toxic doses” as they say.
That looks like a lot of coffee… but then again American coffee is laughably weak =P

Half of the first row of those cups would kill you. This site provides misinformation and should be a crime they can be held responsible for caffeine overdoses

Absolutely, as I pointed out in the post! The coffee mugs are just a visual way of representing the amount of caffeine, really. If you drank it as really strong espressos, I suppose you could OD on caffeine before water, though!

Not quite. The coffee one is very wrong. People have died with 1000mg/1gram of caffeine your average 8oz cup of coffee has about 80-100mg of caffeine just one row of what they show is enough to kill you. The only thing worse than lack of information, is misinformation this site could be held responsible if people think Oh I can drink 30 cups of coffee and be fine.

Hi Eugene. Firstly, please don’t spam the site with comments – one is enough! I’ve removed the others so I can give one concise reply here, to avoid multiple threads.

Secondly, I think you’ve misunderstood the concept of a median lethal dose. These are the doses that would kill 50% of a theoretical test population. In other words, there could certainly be instances where people could take in LESS than the amount indicated and die as a result. There are also cases where someone could ingest MORE than the amount indicated and yet still survive. All of this is clearly explained in the post above, so saying that I could be held responsible for anyone overdosing is a ridiculous suggestion.

As stated above, I consulted with an experienced toxicologist in the making of this graphic, whose job involves detailed knowledge of these figures and how they’re calculated. I trust him to know a lot more about them than I do!

The ethanol one seems off, the LD50 I found for ethanol was around 7060 mg/kg (for rats, I’d assume humans to be similar). for a 75 kg human you’d need 530 g of ethanol. A 45 ml (40% ABV) shot contains 14.2 g of ethanol. Using those figures it’d take 38 shots to reach the LD50 of a 75 kg human. The only way that would change is if our ethanol tolerence is far lower than that of a rat. Did you find a human LD50 for ethanol, I didn’t see it referenced if you did.

Human LD50s are actually notoriously hard to come by, because obviously, it wouldn’t be particularly permissible to carry out LD50 tests on humans! As mentioned in the article, they’re usually converted from animal LD50s, but there’s a degree of unreliability here too. To convert animal doses to equivalent human doses, a scaling factor based on body surface area is often used, so it’s not quite as simple as just looking at the dose for rodents and assuming that that for humans will be the same.

The value given for ethanol here is based on a blood alcohol level of 350mg/dL. The reference for this value is the toxicologist mentioned in the article, who specifically works in post-mortem forensic toxicology, so I trust him to know a good deal more about these values than I do!

This document corroborates the figure of 350mg/dL as the approximate median lethal blood ethanol concentration: http://www.rcpi.ie/content/docs/000001/914_5_media.pdf

Hope that answers your query!

I know on my 18bday I slammed a full bottle of grey goose 40 percent wich at 45ml a shot, 750ml bottle is about 38 shots so yea I’m still here today and that’s more than double the “lethal dose” so much misinformation on this it makes me sick

Stop lying, I have drunk a whole bottle of vodka (750 ml, 42% v/v) in a party in which I was already drunk, and I haven’t died. And I can drink, and I usually drink, 10 to 12 liters of water within one hour or less without having any effect on me

Drinking it over the course of a party isn’t the same as drinking it ALL AT ONCE which is what these figures refer to. The alcohol figure is subject to variation depending on alcohol tolerance, but these figures are based on a blood alcohol concentration of 350mg/dL which was contributed by an experienced post-mortem forensic toxicologist, and is also backed up by this document: http://www.rcpi.ie/content/doc

Additionally, without wishing to call into question your claim, there are documented cases of ‘water drinking competitions’ where contestants have died after drinking the amount specified here. Remember, this is the median lethal dose, so it’s a 50% chance of dying if you ingest that amount. With respect, I very much doubt that you could drink 10-12 litres of water in an hour – there are documented cases of people drinking that quantity over the course of SEVERAL hours and still dying as a result (see here: http://www.telegraph.co.uk/news/uknews/2262683/Man-dies-after-drinking-10-litres-of-water-in-eight-hours.html ).

Good Point, and CRUCIAL detail-all at once vs gradual consumption. With caffeine specifically, “Too Much” is relative to the frequency of consumption, ie 400 mg in one hour vs over the course of the day. In fact there are 3 frequencies caffeine consumers should be aware of: mg caffeine per hour (pacing), mg per day (400mg limit for HEALTH ADULTS), mg per week (dependency). from “Are You a Monster or a Rock Star: a Guide to Energy Drinks – How They Work, Why They Work, How to Use Them Safely”

Haha I’ve slammed a 5th of grey goose that’s equal to 16 shots and it took my BAC to .22 I was really fucked up but the next day I didn’t even have a hangover. Theirs so many videos of rappers doing the exact same on stage with brand new unopened in tampered bottles this site was already wrong with caffeine by a long shot. This is not a credible site.

I wonder how fast the body breaks down Acetaldehyde, since it is far more toxic than ethanol (LD50 1.9 g/kg compared to ethanol 7 g/k, admittedly both are given by rats, but that is still a significant difference.) I would assume it is greater to that of ethanol. Otherwise it would build up in the body and kill you before the ethanol does.

This is really retarded test as They should show the actual LD50 not fictional cups, the truth is from two big cups of strong cafe sensitive person can feel like ding and end up in shock, hart stop. I my self have had overdose in ordinary strong cafe and it was terrible experience. And then they should put their LD50 and compare it with cannabis and magic mushrooms, to show the truth about that..

Thank you! Caffeine can kill as low as 800 mg or 4-5 8oz cups this site has no credibility

Cannabis – you’d need to consume/smoke around 1500lb (yes, pounds) within 15 minutes to kill 50% of people. And they say weed is dangerous… 😉

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