than nicotine gum. a 2016 study found that smokers were less satisfied and had a lower reduction in cravings with using an iqos than with traditional cigarettes. in the study, smoking trial volunteers switching to an htp, after an initial adjustment period, usually smoked more traditional cigarettes than those not switching, while reporting that they were less satisfying and rewarding than with regular cigarettes. sharper peaks in blood nicotine levels from inhalation cause greater nicotine dependence than oral consumption. nicotine replacement products, for instance, deliver nicotine in a slow, stable manner, which is less addictive. inhaled nicotine enters the blood quicker than oral consumption, and blood nicotine levels halve every one to two hours. nicotine withdrawal causes deteriorating mood and creates a craving for nicotine consumption. pregnancy pregnant women who wish to quit smoking but are unable to are left with few options. as nicotine replacement products are often ineffective for quitting smoking, pregnant women turn to alternatives such as htps. there is no information available on the potential impact of htp emissions from mother to fetus as of 2018. the risk to the fetus from htps during pregnancy is hard to quantify ; although the risk to the fetus is probably less than traditional smoking during pregnancy, the committee on toxicity recommends that expectant mothers completely stop smoking. nicotine is harmful to the infant and the growing adolescent brain, is metabolised much faster while a woman is pregnant, easily passes through the placental barrier, and collects in breast milk. there is also growing evidence that nicotine exposure during pregnancy is linked to early birth, stillbirth, and abnormal brain growth. nicotine may result in adverse effects to the neurological growth of the fetus. nicotine can lead to vasoconstriction of uteroplacental vessels, which reduces the delivery of both nutrients and oxygen to the fetus. as a result, nutrition is re-distributed to prioritize vital organs, such as the heart and the brain, at the cost of less vital organs, such as the liver, kidneys, adrenal glands, and pancreas, which can lead to underdevelopment and functional disorders later in life. animal research in regards to maternal nicotine exposure on rats showed a direct adverse impact on pancreas development by reducing endocrine pancreatic islet size and number, which was accompanied by a decrease in gene expression of specific transcription factors and blood glucose regulating hormones such as insulin and glucagon. affected rats exhibited significant pancreatic dysfunction and glucose intolerance. other animal studies have reported insulin resistance in adult offspring due to maternal nicotine exposure; in animal models, nicotine has also been shown to activate nicotinic acetylcholine receptors (nachrs) in the brain, which regulate brain development. nicotine exposure during the first trimester of pregnancy (2 mg/kg/d) leads to structural changes in the hippocampus and somatosensory cortex in rats. construction tobacco stick; above, disassembled, below, intact. a: reconstituted tobacco film, made of dried tobacco suspension. 70% tobacco, humectants (water and glycerin) to encourage aerosol formation, binding agents, and aroma agents. b: hollow acetate tube. c: polymer film filter cools the aerosol. d: soft cellulose acetate mouthpiece, which mimics the feel of a traditional cigarette. nicotine is released from tobacco heated above 150 °c. the burning process, substances emitted and their levels vary at different temperatures: distillation—the process during which nicotine and aromas are transferred from tobacco to smoke—occurs below 300 °c; pyrolysis occurs around 300 °c–700 °c and involves the decomposition of biopolymers, proteins, and other organic materials and generates the majority of substances emitted in smoke; and combustion occurs above 750 °c and results in the generation of carbon dioxide, carbon monoxide, and water. the temperature the tobacco reaches greatly varies among htps; it depends on the process used to heat the tobacco. for example, heatsticks are heated to a maximum of 350 °c, a temperature sufficient to enable pyrolytic decomposition of some organic materials, while the glo ifuse heats tobacco to around 35 °c. the formation of toxic volatile organic compounds, including formaldehyde, acetaldehyde, and acrolein, have been reported in e-cigarette aerosols at similar temperatures as the iqos; flavoring chemicals in e-cigarettes have been discovered to undergo thermal degradation and contribute significantly to levels of toxic aldehydes emitted in e-cigarette aerosols, as demonstrated by the presence of carbon monoxide (co), nitrogen oxides, soot or tars, and aldehydes in emissions. gases, liquid, and solid particles are also found in the emissions; the solids in the emissions have been called nicotine-free dry particulate matter rather than tar in papers written by people connected to the tobacco industry. since the constituents of heatsticks may differ from combustible cigarettes, including flavourants and additives, it is plausible that the iqos aerosol may contain substances not found in tobacco smoke. the emissions of the iqos heatsticks and the iqos menthol mini-cigarettes contain about three times the amount of water and about half the amount of tar found in traditional cigarette emissions. the iqos heatsticks do not generate a flame, but are charred after use. until 2016, phillip morris international researchers stated their iqos product produces smoke. the htp consists of three components with different functions: the processed tobacco stick; a pen-like heater (holder) that the tobacco stick is inserted, which is then heated by an electrically controlled heating element; and a charger that recharges the heater after use. the heated tobacco products automatically stops the heating process after six minutes or 14 moves(puffs) so that pyrolytic products and pollutant release are limited in time as well as by a maximum number of puffs per stick. htps may not generate side-stream smoke because they do not fully combust, but the temperatures reached are sufficient for pyrolysis to happen. there are devices that use a reaction that resembles pyrolysis or combustion, but research has not determined which of the two it is. the tobacco stick contains a compressed tobacco film made of a dried tobacco suspension that has been rolled up into a paper-thin brown tobacco foil and several filter elements. this film consists of about 70% tobacco, as well as humectants (such as water and glycerin, to prevent the tobacco from drying out and promote aerosol formation), binders, and flavorings. the filter elements consist of two independent systems: a polymer film filter that cools the aerosol, and a soft cellulose acetate mouthpiece filter that mimics the sensory aspects of a traditional cigarette. tobacco film (right side) following use. htps are battery-powered systems that produce nicotine-containing emissions by heating tobacco. for this purpose, tobacco sticks are placed in a corresponding heater and heated to about 250–350 °c (around 500 °f), which result in nicotine-containing emissions that are inhaled via a mouthpiece with a filter segment. htps are hybrids between electronic and conventional cigarettes: they are equipped with a device that heats the product without reaching combustion to generate aerosol, while using "real" tobacco instead of nicotine-containing liquids. there are products that have a time limit so that the user is forced to inhale the nicotine within 3.5–10 minutes prior to the device turning off. this function helps support blood nicotine peaks that result in an increased nicotine dependence. there are three general types of heated tobacco products. one that immediately heats processed tobacco to generate aerosol, another that uses processed tobacco that is heated in (but not generate) an aerosol, and one where the processed tobacco gives flavour to the aerosol as the latter moves over the former. htps heat tobacco leaves at a lower temperature than traditional cigarettes. another type of htp is the loose-leaf tobacco vaporizer that involves putting loose-leaf tobacco into a chamber that is electrically heated with an element. history steam hot one, a japanese variant of the eclipse made by japan tobacco.philip morris' heatbar pictured without a specifically designed cigarette. as early as the 1960s, the tobacco companies developed alternative tobacco products to supplement the cigarette market. the first commercial htp was the premier by r. j. reynolds, a smokeless cigarette launched in 1988 and described as difficult to use. many smokers disliked the taste, and it was not popular with users when it was test-marketed in arizona and missouri. it was shaped like a traditional cigarette, and required combustion to move the smoldered charcoal past processed tobacco containing more than 50 percent glycerin to create an aerosol. in 1989, after spending $325 million, r. j. reynolds pulled the premier from the market after the american medical association and other organizations recommended that the us food and drug administration (fda) restrict it or classify it as a drug. the premier product concept was developed further and re-launched as the eclipse in the mid-1990s, which was available in limited distribution as of 2015, and promoted via viral marketing. reynolds american also introduced a brand called revo and stated that it was a "repositioning" of the eclipse. the revo was withdrawn in 2015. the steam hot one was sold in japan by japan tobacco. in october 1998, philip morris launched the accord in the us. it was a specialised cigarette was designed to be used with the electric heating system. advertisements stating reduced risk were drafted for the accord in the us, but were never released. in 1998, the company launched the accord in osaka, japan, and renamed it oasis. the battery-powered, pager-size product was marketed as "low-smoke". an attempt was made in 2007 by kenneth podraza, the vice president of research and development at philip morris in the us at the time, to get the surgeon general of the united states to endorse it. the surgeon general did not reply to podraza's letter. few people used the accord, and most of them also continued to use traditional cigarettes. the accord ceased production in 2006. in 2007 philip morris international launched the heatbar, which was very similar to the accord. it was around the size of a mobile phone and was said to heat specially-designed cigarettes rather than burning them. the heatbar did not obtain any significant user reception, and was discontinued after the only benefit found was to lower second-hand smoke. the accord and heatbar are predecessors of philip morris international's current htps. htps were not a commercial success, and most of them were quickly taken off the market following their debut. in years leading up to 2018, increased tobacco control measures have directed the tobacco industry to develop alternative tobacco products, such as htps. there has been a global decline in tobacco consumption that, if continued, will negatively impact the tobacco industry's profits, which has forced the industry to invent and market new products like htps. the introduction of htps may also have been a response to the growing popularity of e-cigarettes beginning around 2007 after independent companies introduced them before major multinational tobacco companies entered the e-cigarettes market. the global decline of cigarette consumption and decrease in adult smoking prevalence (from 24% in 2007 to 21% in 2015), combined with the success of tobacco control, including the implementation of the who framework convention on tobacco control, may also have led the tobacco companies to consider alternative products to protect their profits and political interests. t.l. caputi suggests that the ubiquity of e-cigarettes and the growing dissatisfaction with not providing a "throat-hit" may present an opportunity for htps. philip morris international anticipates a future without traditional cigarettes, but campaigners and industry analysts question the probability of traditional cigarettes being overshadowed by either e-cigarettes or other products like the iqos. products heated tobacco product. a) charger (left) and holder (right), b) tobacco stick (left) and holder with tobacco stick inserted (right), c) disassembled holder, with heating element visible (left) and the holder's lid (right). htps use a heating system where the tobacco is heated and aerosolised. in addition to nicotine, they contain additives that are flavoured and derived from substances other than tobacco. evidence shows that the concentrations of nicotine in mainstream htp aerosols are lower than in cigarette smoke. smokers regularly reported htp use to be less satisfying than smoking a cigarette. tested htps provided more nicotine in the aerosol than a cigalike e-cigarette but not as much nicotine compared with a tank-style e-cigarette. htps are designed to be similar to their combustible counterparts by replicating the oral inhalation and exhalation, taste, rapid systemic delivery of nicotine, hand-to-mouth feel and throat hit sensations (depending on the temperature) when smoking traditional cigarettes. htps aim for a