Nicotine - Toxicology

Toxicology

The LD₅₀ of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 30–60 mg (0.5–1.0 mg/kg) can be a lethal dosage for adult humans. Nicotine therefore has a high toxicity in comparison to many other alkaloids such as cocaine, which has an LD₅₀ of 95.1 mg/kg when administered to mice. It is unlikely that a person would overdose on nicotine through smoking alone, although overdose can occur through combined use of nicotine patches or nicotine gum and cigarettes at the same time. Spilling a high concentration of nicotine onto the skin can cause intoxication or even death, since nicotine readily passes into the bloodstream following dermal contact.

Historically, nicotine has not been regarded as a carcinogen and the IARC has not evaluated nicotine in its standalone form and assigned it to an official carcinogen group. While no epidemiological evidence supports that nicotine alone acts as a carcinogen in the formation of human cancer, research over the last decade has identified nicotine's carcinogenic potential in animal models and cell culture. Nicotine has been noted to directly cause cancer through a number of different mechanisms such as the activation of MAP Kinases. Indirectly, nicotine increases cholinergic signalling (and adrenergic signalling in the case of colon cancer), thereby impeding apoptosis (programmed cell death), promoting tumor growth, and activating growth factors and cellular mitogenic factors such as 5-LOX, and EGF. Nicotine also promotes cancer growth by stimulating angiogenesis and neovascularization. In one study, nicotine administered to mice with tumors caused increases in tumor size (twofold increase), metastasis (nine-fold increase), and tumor recurrence (threefold increase).

Though the teratogenic properties of nicotine may or may not yet have been adequately researched, women who use nicotine gum and patches during the early stages of pregnancy face an increased risk of having babies with birth defects, according to a study of around 77,000 pregnant women in Denmark. The study found that women who use nicotine-replacement therapy in the first 12 weeks of pregnancy have a 60% greater risk of having babies with birth defects, compared to women who are non-smokers. Nicotine use among pregnant women has also been correlated to increased frequency of ADHD. Children born to mothers who used tobacco were two and a half times more likely to be diagnosed with ADHD. Tanya Froelich estimated that "exposure to higher levels of lead and prenatal tobacco each accounted for 500,000 additional cases of ADHD in U.S. children".

Effective April 1, 1990, the Office of Environmental Health Hazard Assessment (OEHHA) of the California Environmental Protection Agency added nicotine to the list of chemicals known to the state to cause developmental toxicity, for the purposes of Proposition 65.