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: 
When exploring whether nicotine is toxic to humans, the discussion isn't complete without the inclusion of non-adult humans / humans-in-development. Nicotine is toxic to humans beginning at conception. Nicotine has adverse effects on sperm, making them malformed, less likely to fertilize eggs, and making the embryos they do create less likely to survive. Mohamad Eid Hammadeh, PhD, professor of obstetrics and gynecology a the University of the Saarland, Homburg/Saar, Germany, in an interview with WebMD, is quoted as saying, 

"The DNA alphabet of these sperm has one or two letters missing. And this cannot be repaired. When we inject these damaged sperm into an egg cell, the sperm is not capable of fertilizing the cell. And even if it does, the [miscarriage] rate is very high."

[This paper](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719292/pdf/JRI-12-201.pdf) talks about the abnormalities seen in sperm exposed to nicotine, whether sperm can recover, and after how long.

[This paper](http://jnci.oxfordjournals.org/content/89/3/238) links the nicotine consumption of fathers to their children's likelihood of developing childhood cancer, citing one possible explanation that smoking causes genetic damage to sperm cells. The sperm cell mutations then become inborn cancer-causing mutations in the offspring.

They jury may be out on the extremity of nicotine's impact on adult health, but it's clear that it's deleterious to the next generation.
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880486/>

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