Question: More specifically, is nicotine in the concentrations that smokers receive when smoking cigarettes toxic? I know that in great enough concentrations it can be toxic (but then, so can just about anything else, including oxygen) and I know that in plants it is used as a defense against insects and can even be used as an insecticide. However, it has always been my understanding that nicotine is irrelevant as far as the harmful effects of smoking go. 

I recently had a conversation with another biologist who had just quit smoking and had done quite a bit of research on the subject. He said that nicotine itself is in fact bad for you and, therefore, that tobacco-less alternatives to cigarettes (such as electronic cigarettes) are still harmful **because of the nicotine alone**. 

Does anyone have any more information on this? Perhaps some references? Or, even better, a detailed explanation of the pathways involved? Again, I stress, not about nicotine's toxicity in general but about its harmful effects on vertebrates (preferably human) at the kinds of concentrations one could expect to ingest when smoking.

Answer: 
I think its useful to say that nicotine is not very toxic to humans - cells don't die or get sick for typical smoking habits. Secondary health effects are possible, but here is a toxicological profiles. 

Nicotine is a toxin in large enough quantities and nicotine has an LD50 (lethal dose for 50% of individuals) of [0.5-1 mg Nicotine / kg of body weight](http://en.wikipedia.org/wiki/Nicotine_poisoning#Toxicology). So even a small spill on your skin of the chemical can be life threatening, but for smokers the nicotine itself is not dangerous. 

Individuals who smoke intake about 1 mg per cigarette smoked. So a small adult (110 lbs) can smoke 25 cigarettes in a short period of time (or all at once!) and just barely get to the bottom end of that limit. Nicotine is water soluble and clears out through the urine at a fast rate though - half of the nicotine from a cigarette is cleared from your system within 2 hours, which means that 4-5 pack a day smokers are not really killing themselves (from nicotine). 

That being said, children are about 5-10 times more sensitive than adults, so even 5-6 cigarettes in an hour can be toxic. That's quite a bit of smoking though. 

Not all animals have the same relationship to the nicotinic acetylcholine receptors as humans do. [Nicotine is toxic to insects and will kill an insect in a matter of minutes or hours](http://en.wikipedia.org/wiki/Insecticide#Neonicotinoids). Rats are about 50x less sensitive than people. 

I think its comparable to the question of whether caffeine is harmful to people. In the amount we consume it, sometimes up to grams a day, there is no obvious common side effect, but you figure that decades later it will show up as a problem - a difficult connection to prove.
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880486/>

Suggesting that the LD50 is an oral LD50 of 6.5–13 mg/kg.