Environmental tobacco smoke can be evaluated either by directly measuring tobacco smoke pollutants found in the air or by using biomarkers, an indirect measure of exposure. Carbon monoxide monitored through breath, nicotine, cotinine, thiocyanates, and proteins are the most specific biological markers of tobacco smoke exposure.[78][79] Biochemical tests are a much more reliable biomarker of second-hand smoke exposure than surveys. Certain groups of people are reluctant to disclose their smoking status and exposure to tobacco smoke, especially pregnant women and parents of young children. This is due to their smoking being socially unacceptable. Also, it may be difficult for individuals to recall their exposure to tobacco smoke.[80] A 2007 study in the Addictive Behaviors Journal found a positive correlation between second-hand tobacco smoke exposure and concentrations of nicotine and/or biomarkers of nicotine in the body. Significant biological levels of nicotine from second-hand smoke exposure were equivalent to nicotine levels from active smoking and levels that are associated with behaviour changes due to nicotine consumption. Nicotine is an alkaloid found in the nightshade family of plants (Solanaceae) that acts as a nicotinic acetylcholine receptor agonist. The biosynthesis takes place in the roots and accumulation occurs in the leaves of the Solanaceae. It constitutes approximately 0.63.0% of the dry weight of tobacco and is present in the range of 27 g/kg of various edible plants. It functions as an antiherbivore chemical; therefore, nicotine was widely used as an insecticide in the past and nicotine analogs such as imidacloprid are currently widely used. In low doses (an average cigarette yields about 1 mg of absorbed nicotine), the substance acts as a stimulant in mammals, while high amounts (3060 mg) can be fatal. This stimulant effect is the main factor responsible for the dependence-forming properties of tobacco smoking. According to the American Heart Association, nicotine addiction has historically been one of the hardest addictions to break, while the pharmacological and behavioral characteristics that determine tobacco addicti n are similar to those determining addiction to heroin and cocaine. The nicotine content of popular American-brand cigarettes has slowly increased over the years, and one study found that there was an average increase of 1.6% per year between the years of 1998 and 2005. This was found for all major market categories of cigarettes. Research in 2011 has found that nicotine inhibits chromatin-modifying enzymes (class I and II histone deacetylases) which increases the ability of cocaine to cause an addiction. Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after the French ambassador in Portugal, Jean Nicot de Villemain, who sent tobacco and seeds to Paris in 1560, and who promoted their medicinal use. The tobacco and seeds were brought to ambassador Nicot from Brazil by Luis de Gois, a Portuguese colonist in Sao Paulo. Nicotine was first isolated from the tobacco plant in 1828 by physician Wilhelm Heinrich Posselt and chemist Karl Ludwig Reimann of Germany, who considered it a poison. Its chemical empirical formula was described by Melsens in 1843, its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893, and it was first synthesized by Ame Pictet and A. Rotschy in 1904. [edit]Historical use of nicotine as an insecticide Tobacco was introduced to Europe in 1559, and by the late 17th century, it was used not only for smoking but also as an insecticide. After World War II, over 2,500 tons of nicotine insecticide (waste from the tobacco industry) were used worldwide, but by the 1980s the use of nicotine insecticide had declined below 200 tons. This was due to the availability of other insecticides that are cheaper and less harmful to mammals. Currently, nicotine is a permitted pesticide for organic farming because it is derived from a botanical source. Nicotine sulfate sold for use as a pesticide is labeled "DANGER," indicating that it is highly toxic. However, in 2008, the EPA received a request to cancel the registration of the last nicotine pesticide registered in the United States. This request was granted, and after 1 January 2014, this pesticide will not be available for sale.