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Systems toxicology investigations indicated that nicotine exposure also affected metabolic pathways the in liver, including upregulation of fatty acid beta-oxidation, cholesterol synthesis, gluconeogenesis, and ketone body formation pathways

While in 1964, the Surgeon General Report on Smoking and Health or Terry Report 8 declared that tobacco smoking was causally associated with lung cancer and then evidence emerged showing its association with many other diseases, it was only in 2004 that SHS has been classified as a carcinogen by the World Health Organizations Agency for Research on Cancer 9 , finally defeating tobacco industry attempts to obstruct the publication of this monograph to prevent increased smoking restrictions 10

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