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A recent question on poisons was answered in part by bringing up the concept of $\pu{LD_{50}}$ and animal testing and so on; none of that was new to me, but it did bring to mind a question I don’t know the answer to:

Has there ever been a substance that scientists have actively tried to determine $\pu{LD_{50}}$ for, and could not because they were unable to determine a dosage low enough to kill “just” half of the subjects?

Please note that this question is not restricted, strictly, to any technical definition of “poison.” Rather, answers must meet these requirements:

  1. There must be research (considering that I am looking for something that might be a negative result and those do not get published as much as they should be, I won’t demand peer-reviewed publication, but the goal should have been to attempt peer-review publication if it had worked out—effectively, I mean serious work), and

  2. that research must use the term “$\pu{LD_{50}}$” to characterize the substance.

Basically, I don’t want to get into debates about what is, or is not, a poison here. If a researcher is willing to call something $\pu{LD_{50}}$, then I am willing to accept it as a “poison” for the purposes of this question.

I also don’t want speculation, or for a user here to characterize something as $\pu{LD_{50}}$ when the underlying research doesn’t call it that. It is not enough to say, for example, “well I’m sure even a single atom of antimatter inside your body would be pretty bad,” you need to cite a particular researcher who has performed experiments with the goal of determining what they themselves called $\pu{LD_{50}}$ for that substance.

I suspect the answer is no, but I have no idea how to research something like this.

KRyan
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2 Answers2

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Of course no. Botulotoxin is probably the strongest known, and still its $\rm LD_{50}$ is counted in nanograms per kilogram, which is pretty manageable. Sure, working with such tiny amounts requires some special measures, but still, it is way greater than one molecule. You can divide it again, and again, and again.

So it goes.

Ivan Neretin
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  • Thanks; I’d heard botulotoxin referred to as the strongest, but I wasn’t sure that there might not be caveats to that, strongest with the $\pu{LD_{50}}$ actually measured or something. – KRyan Jan 16 '18 at 16:08
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    "one prion molecule makes two - those two go on and make four, those four make eight, and so on, until the whole brain is just one liquifiied spongy mass. " https://blogs.scientificamerican.com/a-blog-around-the-clock/bio101-protein-synthesis-transcription-and-translation/ I wouldn't rule out one prion molecule delivered in a particular way killing (slowly) more then 50% of the people. – DavePhD Jan 16 '18 at 16:57
  • @DavePhD It's not like you have LD50 for them, also you vastly overestimate their power. Organisms have ways to deal with misfolded proteins. BTW this is supposed to be about poisons and blogs on sci. amer. aren't good sources. – Mithoron Jan 16 '18 at 17:07
  • @Mithoron Technically, the only requirement I have for a substance here is that someone tried to determine an $\pu{LD_{50}}$ for it. If it’s not technically a poison per se, but harmful in some other way (e.g. these prions, or Bill K’s suggestion of uranium), it counts as long as someone’s tried to get an $\pu{LD_{50}}$. Let me know (or feel free to edit yourself) if you think the question needs more clarification on that point. – KRyan Jan 16 '18 at 17:49
  • @Mithoron I'm with DavePhD on this one... One single virion or prion can be easily enough to kill an adult human, if the immune system is compromised or the virus/prion is "new" and/or "smart" enough for the immune system to overlook it for a couple of days. Some viruses do just that - they replicate slowly so that the immune system's defense reaction is not triggered shortly after the infection (as that triggering usually requires a rapid increase in pathological activity in short time), and when the immune system "notices" the virus, it is compromised by the virus already (HIV virus). –  Jan 16 '18 at 17:58
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    @vaxquis that kind of "if" does not an LD50 make. – hobbs Jan 16 '18 at 18:05
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    Seeing as I’m the one who asked the question, I think I’m entitled to determine what it’s asking about, not you. Yes, I understand that $\pu{LD_{50}}$ is typically used for toxicants, would not generally be used for pathogens, etc. But the definition of $\pu{LD_{50}}$ really is compatible with anything that might, at some dosage, kill 50% of subjects. And while scientists would almost never use it that way, almost never is not the same as never. If a researcher decided to use $\pu{LD_{50}}$ as a measure of a substance’s danger, that is good enough for me here. – KRyan Jan 16 '18 at 18:10
  • (But it does have to be an actual research effort made to determine “the LD50LD50\pu{LD_{50}} of X,” not just some speculative answer here suggesting that if someone were to try to do so with some dangerous substance, it would meet the criteria of the question. I am using the “research effort made” standard as the bar to meet to qualify as counting as an “LD50LD50\pu{LD_{50}},” as a valid answer to the question.) – KRyan Jan 16 '18 at 18:12
  • It's not even that easy to draw a line between prions and toxins, considering that prions are just proteins, just like e.g. botulotoxin. – jpa Jan 16 '18 at 20:15
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    Botulotoxin doesn't reproduce. I think that's quite a solid line. – Ivan Neretin Jan 16 '18 at 20:44
  • @IvanNeretin Just so you know, I did update the question to clarify what I meant, in case that changes your answer. I suspect it doesn’t, and I suspect that this is still the correct answer, but since there had been some confusion (and because another answer asserted that $\pu{LD_{50}}$ actually has been used for e.g. prions, though it’s difficult for me to confirm that this is the case), I have un-accepted this answer for now. In all likelihood I will end up coming back and accepting this answer again, but thought you deserved the head’s up. – KRyan Jan 16 '18 at 21:16
  • Well, that makes it quite a bit harder to answer. I think I'd rather not change my answer, even though prions might now be a viable candidate. – Ivan Neretin Jan 16 '18 at 21:21
  • Right, that’s why I didn’t just look up the deadliest toxin, see it had a documented $\pu{LD_{50}}$, and consider my question answered. Anyway, thanks again for the answer in any event. – KRyan Jan 16 '18 at 21:34
  • Folks, please take these side discussions to the chatroom that was automatically made for the comments under the question. This is really not what comments are made for. Thanks! – jonsca Jan 16 '18 at 21:35
  • Otherwise said no homeopathic poison exidt :) – Alchimista Jan 17 '18 at 09:44
  • Wouldn't prions be more of a biological than chemical hazard, just like a virus? – rackandboneman Jan 17 '18 at 10:29
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Some options that do not work, but have been suggested:

  1. Prions: looks like LD50 has been successfully determined for the most common Sc237 and 263K prions: Prions: A Challenge for Science, Medicine, and the Public Health System. Though it is also referred to as "Infectious dose" as opposed to "Lethal dose".

  2. Polonium: While some sources claim that polonium cannot be characterized by LD50, this is not due to high lethality but just because the effects vary depending on what kind of cancers or acute radiation disease the radiation causes. Actual LD50 is around 90 ng for humans for acute radiation disease.

  3. Antimatter: looks like around 1 ng would be plenty to kill a person. LD50 would be much lower, but probably easy enough to measure anyway. Real problem in the experiment would be delivering the antimatter without premature annihilation.

But in reality, it just depends on the means available to the scientist trying to determine the LD50. For example in this study, "For the remaining solvents LD50 could not be determined due to volume limitations, and have been given a value of <1.0 ml/kg."

The limit of current science would have to be a poison that would kill with a single molecule, as it is quite possible nowadays to manipulate and separate single molecules. Or otherwise single indivisible unit, such as a single cell.

jpa
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  • Please limit your answer to only those substances that have had actual research into determining their “$\pu{LD_{50}}$.” So that book on prions might work (though it’s unclear to me since only one page appears to use the term and I don’t get to see enough context to see if they’re actually discussing the $\pu{LD_{50}}$ of the prions), maybe polonium. Also, things that do have an $\pu{LD_{50}}$ aren’t actually answers to the question; they could be useful if you can prove they are as deadly as things can possibly get (suggesting that the answer to the question is no). – KRyan Jan 16 '18 at 20:59
  • @KRyan, well, if you want to be nitpicky like that, I'll just point to the second last paragraph that fits the nitpicky interpretation of your question by having a group of scientists who were actively trying to determine LD50 and couldn't. – jpa Jan 16 '18 at 21:20
  • I don’t consider it nit-picky at all; a question open-ended enough to allow random speculation like antimatter here should have been closed as being overly-broad and/or primarily opinion-based. Anyway, yes, the second paragraph could work, except I have absolutely no way of confirming your assertions here. A link to the work would improve matters tremendously. Note the updates to the question clarifying matters. – KRyan Jan 16 '18 at 21:22
  • Yeah, paywalls suck. If you want, searching for that phrase on google scholar should (I think) show that it does exist there even if you don't have access to the full text. – jpa Jan 16 '18 at 21:26
  • This is about #1 again? Yeah, I tried that, only got one hit (and one false-positive for a citation abbreviated as LD), which did talk about $\pu{LD_{50}}$ but it wasn’t clear what substance was being discussed in that section, and I couldn’t get at the surrounding context. Certainly not enough to see that they attempted to determine an $\pu{LD_{50}}$ but could not due to being unable to isolate a small enough dosage. – KRyan Jan 16 '18 at 21:32
  • Still would like to see the “other” sources for #2 (the ones that aren’t the “some” that say you cannot characterize polonium with $\pu{LD_{50}}$) that do talk about it having an $\pu{LD_{50}}$, though again if they were able to actually determine a dosage than it isn’t quite an answer to the question. Though again, if you want to answer no and then use prions and polonium as evidence of even ridiculously dangerous things that nonetheless we could get an $\pu{LD_{50}}$ for, that’s fine—but you have to actually spell out that this is your answer in your answer to do that. – KRyan Jan 16 '18 at 21:32
  • (As above)

    Folks, please take these side discussions to the chatroom that was automatically made for the comments under the question. This is really not what comments are made for. Thanks!

     – jonsca Jan 16 '18 at 21:37
  • @jonsca Actually for what it’s worth, in my opinion, all of these comments are directly pertinent to attempting to improve the answer, not side discussions. If jba is not going to act on them, they may be obsolete and worthy of migrating to chat or deleting, but at least in my opinion it has not been long enough for that (but then I am not very familiar with this Stack, and certainly haven’t seen what flags have been raised here). On the other answer, I agree. – KRyan Jan 17 '18 at 04:20
  • @KRyan I think the initial confusion was about my list. I did clarify that to "Options that have been suggested but do not work:". As for what is closest to a real answer I have, is the study with "For the remaining solvents LD50 could not be determined.." but the full text to that is unfortunately paywalled. – jpa Jan 17 '18 at 07:25
  • About antimatter. Shouldn't ng of antimatter simply destroy ng of matter? Would initiate a cascade? – Alchimista Jan 17 '18 at 09:56
  • @Alchimista It would destroy a nanogram of matter, yes, and release a lot of energy in the process. 180 kJ for a nanogram, enough to heat 0.7 kg of surrounding tissue to boiling point. – jpa Jan 17 '18 at 10:46
  • Forgot that! :)) – Alchimista Jan 17 '18 at 10:48