In large enough transdermal/oral overdose "no pulse within 1-2 minutes of ingestion"
https://sci-hub.se/10.1016/0736-4679(91)90318-A
... but I would only consider it a method of last resort. The most dangerous chemical I ever encountered or dealt with was pure pharmaceutical, technical-grade 99.999% molecular purity nicotine. Not concentrate or extract - the straight up chemical.
I was a partner in one of the first-mover umbrella of vaping e-commerce retail ventures back in 2008 as a technical director overseeing the procurement, production, QA and distribution of electronic cigarettes ( or "eCigs" as they were called back then before vaping became a buzzword), but on the laboratory and technical backend side.
One drop of pure 99.999% technical-grade nicotine would be enough to kill four horses since it's transdermal and cardiotoxic, resulting in death within minutes or hours. One of our lab techs died after accidentally spilling a few droplets on his skin. By the time EMS arrived he was pronounced dead. I didn't have the guts to see the CCTV footage for myself, but from witness accounts it was horrid (rabid, foaming at the mouth). Another lab tech had to be rushed to the ER after merely leaving an open container of pure nicotine technical $99.9999 concentrate who started drooling and fell ill as the vapors bled out into the confied space but made it out okay after being rushed to ER.
I'm not talking about eJuice; I'm talking about the crude, raw, pure native molecular liquid chemical Nicotine in the purest 99.999% lab-tech-grade form you can only get from B2B chemical manufacturers or China. I remember holding a one-liter bottle in HazMat suit and just wondering, Wow, there's enough venom concentrate here to instantly euthanize half a million people, in the least.
"Nicotine acts by direct stimulation of the nicotinic
subset of central and peripheral acetylcholine receptors
(Figure 1). Nicotine poisoning may produce myriad
Nicotine 135 symptoms (Table 1). A patient who is mildly to moder-
ately toxic may present with the classical findings of
cholinergic excess, such as muscle fasciculations and
muscarinic symptoms (pupil constriction, salivation, tearing up,
urination, defecation, sweating, vomiting, coughing and increased pulmonary secretions). These oc-
cur due to parasympathetic ganglionic stimulation at
nicotinic receptor sites. In such cases, the presentation
may be identical to that of an organophosphate expo-
sure, and atropine may be beneficial (6).
At larger doses, the initial stimulatory effect on most
end organs is rapidly followed by prolonged ganglionic
and neuromuscular blockade resulting from persistent
membrane depolarization.
With ganglionic blockade,
muscarinic findings are no longer produced since nico-
tine does not stimulate effector cell muscarinic receptors
directly (12). Therefore, atropine would not be of
benefit in such circumstances. This is in contradistinc-
tion to serious organophosphate poisonings, where mus-
carinic effects continue to be produced by direct acetyl-
choline stimulation. Muscarinic effecters are not subject
to depolarization blockade (12). Atropine (along with
2-PAM) is the treatment of choice in these cases.
Serious nicotine ingestions frequently result in rapid
progression to hypotension and death. The most com-
mon mechanisms of death are respiratory arrest pro-
duced by peripheral neummuscular blockade, and cardiovascular
collapse (2,11,12). In our case death was secondary to
nicotine-induced cardiopulmonary arrest and hypoxic
brain damage."
