It is correlated with a number of adverse effects such as dental disease, oral cancer, oesophagus cancer, and pancreatic cancer, cardiovascular disease, asthma, and deformities in the female reproductive system. A correlation was identified between smokeless tobacco and risk of fatal coronary artery disease and fatal stroke. Use of smokeless tobacco also seems to greatly raise the risk of non-fatal ischaemic heart disease among users in Asia, although not in Europe. It is estimated the safety risk of smokeless tobacco is similar to that of electronic cigarettes, which has about 1% of the mortality risk of traditional cigarettes. Smokeless tobacco is not a healthy alternative to cigarette smoking. There is no safe level of smokeless tobacco use. The declines in smokeless tobacco initiation among adolescents and young adults is particularly relevant to improving the health of the nation because smokeless tobacco use is often linked to subsequent cigarette initiation. Smokeless tobacco users can experience these negative health consequences at any age. Smokeless tobacco accounts for an abundance of deaths globally with a significant proportion of them attributed to Southeast Asia. Youth use of tobacco in any form is unsafe. Carcinogenicity All tobacco products contain toxicants, and smokeless tobacco products contain cancer-causing chemicals. The carcinogenic compounds occurring in smokeless tobacco vary widely, which rely upon the kind of product and how it was manufactured. A 2017 review found "Overall, 28 carcinogens have been rigorously identified across a range of major smokeless tobacco products, primarily from 3 groups of compounds: nonvolatile, alkaloid-derived TSNAs; N-nitrosoamino acids; and volatile N-nitrosamines. Among these carcinogens, researchers identify TSNAs as the most abundant in smokeless tobacco and the most carcinogenic." The amounts of nicotine in saliva from using smokeless tobacco could be at amounts that can cause cytotoxicity, according to in vitro studies. Other chemicals found in tobacco can also cause cancer. These include: A radioactive element (polonium-210) found in tobacco fertilizer. Chemicals formed when tobacco is cured with heat (polynuclear aromatic hydrocarbons—also known as polycyclic aromatic hydrocarbons). Harmful metals (arsenic, beryllium, cadmium, chromium, cobalt, lead, nickel, mercury). Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are