Nicotine Toxicity, Poisoning and Safety

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1. The Papers
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The Papers (26)

Newest first. Study types on this page — Human observational study: 3 · Review: 17 · Animal study: 5 · Other: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Nicotine on the developing brain

Review, 2023. This review gathers research in people and in laboratory animals on how nicotine affects the brain when exposure happens during pregnancy or the teenage years, periods when the brain is still developing and especially easy to change. The authors report that nicotine exposure in these windows harms heart and breathing function, learning and memory, decision-making and planning skills, and the brain's reward circuits. They also describe effects that last into adulthood, including lasting changes to how genes are switched on that can be passed to later generations. The authors note that non-smoked nicotine products are widely used by pregnant women and teenagers because people wrongly believe they are safe.

Castro EM, Lotfipour S, Leslie FM (2023). Nicotine on the developing brain. Pharmacol Res. — PubMed PMID: 36868366 · doi:10.1016/j.phrs.2023.106716

Prenatal Nicotine Exposure Induces Low Birthweight and Hyperinsulinemia in Male Rats

Animal study, 2021. This study was done in rats, not people. Researchers gave nicotine to pregnant rats and found that their pups were born lighter and stayed smaller at weaning than pups from untreated mothers. When the offspring were later fed a high-fat diet, their blood sugar was the same as in the control rats, but insulin levels rose only in the males from nicotine-treated mothers, and those males also had fewer insulin receptors in the liver. The authors conclude that nicotine exposure before birth led to high insulin levels in male rats given a high-fat diet, and that fewer insulin receptors in the liver may help explain it.

Nemoto T, Ando H, Nagao M et al. (2021). Prenatal Nicotine Exposure Induces Low Birthweight and Hyperinsulinemia in Male Rats. Front Endocrinol (Lausanne). — PubMed PMID: 34177815 · doi:10.3389/fendo.2021.694336

Special Issue on the Effects of Prenatal Smoking/Nicotine Exposure on the Child's Health

Other, 2021. This is a short editorial introducing a special journal issue about how a child's health is affected when the mother smokes or is exposed to nicotine during pregnancy. It is not a study and reports no new data. The editorial notes that smoking raises the risk of poor outcomes during pregnancy and around birth, and may harm the child's health in the short and long term.

Ekblad MO, Blanc J, Berlin I (2021). Special Issue on the Effects of Prenatal Smoking/Nicotine Exposure on the Child's Health. Int J Environ Res Public Health. — PubMed PMID: 34065326 · doi:10.3390/ijerph18105465

National Estimates of ENDS Liquid Nicotine Exposures, U.S., 2013-2017

Human observational study, 2020. This study used a U.S. national injury surveillance database to estimate hospital emergency department visits caused by exposure to the liquid nicotine used in e-cigarettes, among people aged 5 years and older, from 2013 to 2017. An estimated 2,718 such cases were treated in U.S. emergency departments over that period, most often in people aged 25 or older (51.7%), white (74.1%) and male (51.9%). Poisoning was the most common diagnosis (82.7%), the most common symptoms involved the heart and circulation (29.7%), and most patients were treated and released, while 7.5% were admitted to hospital. The authors note that no long-term health outcome studies of liquid nicotine exposure are available yet, and say the findings may help shape education programs aimed at preventing these exposures.

Chang JT, Wang B, Rostron BL et al. (2020). National Estimates of ENDS Liquid Nicotine Exposures, U.S., 2013-2017. Am J Prev Med. — PubMed PMID: 32826127 · doi:10.1016/j.amepre.2020.05.027

Vaping implications for children and youth

Review, 2020. This review looks at how e-cigarettes work, what they do to health, how many young people use them, and how they are regulated. It reports government survey figures showing that 27% of high school students had used a tobacco product in the past month, mostly e-cigarettes (20.8% of high school students), and says vaping has reversed a decades-long decline in nicotine use among young people. Besides long-term nicotine addiction, the authors describe growing reports of short-term harms in young people, including seizures, acute nicotine poisoning, burns and lung injury. They conclude that laws should strictly ban marketing and sales to young people and reduce their access to these products.

Gilley M, Beno S (2020). Vaping implications for children and youth. Curr Opin Pediatr. — PubMed PMID: 32332326 · doi:10.1097/MOP.0000000000000889

Prenatal electronic cigarette exposure decreases brain glucose utilization and worsens outcome in offspring hypoxic-ischemic brain injury

Animal study, 2020. Researchers exposed pregnant mice to vapor from an e-cigarette containing 2.4% nicotine, then studied their offspring's response to a brain injury caused by low oxygen and reduced blood flow, similar to a stroke around birth. Brain cells taken from the exposed fetuses survived less well and used less glucose (sugar) when deprived of oxygen and glucose in the lab. Exposed mouse pups had more brain injury and swelling 24 hours after the injury, and by adolescence they showed worse memory, learning and motor coordination, along with fewer glucose transporters in the brain. These results are only in mice and mouse cells, and the study did not separate the effects of nicotine from the rest of the vapor.

Sifat AE, Nozohouri S, Villalba H et al. (2020). Prenatal electronic cigarette exposure decreases brain glucose utilization and worsens outcome in offspring hypoxic-ischemic brain injury. J Neurochem. — PubMed PMID: 31883376 · doi:10.1111/jnc.14947

Poisoning exposure cases involving e-cigarettes and e-liquid in the United States, 2010-2018

Human observational study, 2020. Researchers looked at poisoning cases involving e-cigarettes and e-liquids that were reported to US poison control centers from 2010 to 2018. Yearly cases rose sharply to a peak of 3742 in 2014, fell each year from 2015 to 2017, then rose by 25.0% between 2017 and 2018 (from 2320 to 2901). About two-thirds (64.8%) of cases were children under age five, and 14.7% were children aged 5-17 or young adults aged 18-24. Life-threatening symptoms were rare (0.1% of cases), and people with more serious outcomes tended to have been exposed to larger amounts of e-liquid or nicotine.

Wang B, Liu S, Persoskie A (2020). Poisoning exposure cases involving e-cigarettes and e-liquid in the United States, 2010-2018. Clin Toxicol (Phila). — PubMed PMID: 31496321 · doi:10.1080/15563650.2019.1661426

Toxicity assessment of electronic cigarettes

Review, 2019. This review pulls together laboratory studies in cells and animal studies on how toxic e-cigarettes are, including what part nicotine plays. The studies disagree: some found that nicotine drove the harmful effects and the solvents alone did not, while others found nicotine was not linked to harm and the solvents and flavorings caused considerable damage to cells or animals. Most studies that compared the two found e-cigarettes less toxic than tobacco cigarettes. The authors say the evidence is still not enough because studies did not use standard testing methods, and they call for standardized testing of nicotine, e-liquid ingredients and devices.

Wang G, Liu W, Song W (2019). Toxicity assessment of electronic cigarettes. Inhal Toxicol. — PubMed PMID: 31556766 · doi:10.1080/08958378.2019.1671558

Attenuated Tregs increase susceptibility to type 1 diabetes in prenatal nicotine exposed female offspring mice

Animal study, 2019. This study in mice looked at whether nicotine given to mothers during pregnancy raises the risk of type 1 diabetes in their female offspring. Compared with controls, the exposed offspring weighed less and had higher blood sugar from day 21 to day 42 after birth. By day 42 they also had raised levels of an autoantibody used to detect type 1 diabetes, along with smaller insulin-producing islet areas and fewer beta cells in the pancreas. They also had fewer regulatory T cells, a type of immune cell that helps prevent the immune system from attacking the body, and the authors suggest this drop may explain the diabetes-like changes. These findings come only from mice.

Zhao WH, Wen X, Qu W et al. (2019). Attenuated Tregs increase susceptibility to type 1 diabetes in prenatal nicotine exposed female offspring mice. Toxicol Lett. — PubMed PMID: 31442585 · doi:10.1016/j.toxlet.2019.08.016

Developmental toxicity of e-cigarette aerosols

Review, 2019. This review looks at what is known about using an e-cigarette during pregnancy, which some pregnant women try as a substitute for smoking. The authors point out that the US Surgeon General's report found enough evidence that nicotine harms the health of mothers and unborn babies. Whether e-cigarettes are safer than smoking in pregnancy is still unknown, especially in the first trimester, when the baby's organs are forming. Early evidence also suggests that e-cigarette aerosol without nicotine may harm the developing baby, possibly because of ingredients such as flavorings. The authors call for careful human and animal studies to answer the question.

Greene RM, Pisano MM (2019). Developmental toxicity of e-cigarette aerosols. Birth Defects Res. — PubMed PMID: 31400084 · doi:10.1002/bdr2.1571

Molecular mechanisms for nicotine intoxication

Review, 2019. This review looks at how nicotine poisons the body and the nervous system. Nicotine is one of more than 4700 substances in tobacco smoke and was once used as a pesticide. The authors say poisoning still happens to tobacco farm workers, and to children and adults who swallow nicotine products by accident or on purpose. They cover how the body absorbs and handles nicotine, sudden poisoning (including green tobacco sickness and poisoning from popular nicotine products), changes to the body's daily sleep-wake rhythm, and long-term harm from nicotine exposure before birth, including effects on newborn behavior and sudden infant death syndrome.

Alkam T, Nabeshima T (2019). Molecular mechanisms for nicotine intoxication. Neurochem Int. — PubMed PMID: 30779928 · doi:10.1016/j.neuint.2019.02.006

Differential Effects of Nicotine Exposure on the Hippocampus Across Lifespan

Review, 2018. This review pulls together earlier research on how nicotine affects the hippocampus, a brain area important for learning and memory. Nicotine acts there through nicotinic acetylcholine receptors, which are found throughout the hippocampus's brain circuits. The authors report that both long-term and one-time nicotine exposure affect the hippocampus's structure and function, and the learning and memory that depend on it. These effects differ depending on when exposure happens: around birth, in adolescence, or in old age. The authors conclude that research on nicotine addiction and its treatment should take these age differences in sensitivity to nicotine into account.

Zeid D, Kutlu MG, Gould TJ (2018). Differential Effects of Nicotine Exposure on the Hippocampus Across Lifespan. Curr Neuropharmacol. — PubMed PMID: 28714396 · doi:10.2174/1570159X15666170714092436

Tobacco Harms, Nicotine Pharmacology, and Pharmacologic Tobacco Cessation Interventions for Women

Review, 2017. This review looks at the harms of tobacco use for women, how women's bodies respond to nicotine, and the medicines used to help women quit smoking. It reports that women's particular biological response to nicotine may make quitting harder, and that nicotine exposure in the womb has been linked to epigenetic changes (changes in how genes are switched on and off) that can affect later generations. It describes nicotine replacement therapy and two other medicines as first-line quit-smoking medicines, and two further medicines as second-line options, covering how they work, how well they work, and their safety for women who are not pregnant, are pregnant, or are breastfeeding. The authors note there is far less evidence on these medicines in pregnancy, and that any risk to the baby has to be weighed against continued smoking, which always exposes the baby to nicotine.

Baraona LK, Lovelace D, Daniels JL et al. (2017). Tobacco Harms, Nicotine Pharmacology, and Pharmacologic Tobacco Cessation Interventions for Women. J Midwifery Womens Health. — PubMed PMID: 28556464 · doi:10.1111/jmwh.12616

Cardiovascular toxicity of nicotine: Implications for electronic cigarette use

Review, 2016. This review looks at whether nicotine itself harms the heart and blood vessels, as part of the debate over the risks of electronic cigarettes. It explains that nicotine has drug effects that could contribute to sudden heart events and faster buildup of artery plaque, the kind seen in cigarette smokers. Studies of nicotine medicines and smokeless tobacco suggest that nicotine without burned tobacco smoke carries a low heart risk compared with smoking, but it is still a concern for people who already have heart disease. The authors report that e-cigarettes, which deliver nicotine without burning tobacco, appear to carry low heart risk in healthy users, at least with short-term use.

Benowitz NL, Burbank AD (2016). Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. Trends Cardiovasc Med. — PubMed PMID: 27079891 · doi:10.1016/j.tcm.2016.03.001

Electronic Nicotine Delivery Systems

Review, 2015. This is a policy statement from a pediatrics group about e-cigarettes and similar devices. These handheld devices heat a liquid that usually contains concentrated nicotine, flavorings and propylene glycol, and the user breathes in the resulting aerosol. The authors say nicotine is highly addictive and toxic, and that other toxic substances, cancer-causing chemicals and metal particles have been found in the liquids and aerosols. Reports to US poison control centers of children poisoned by the liquid have been rising, with at least 1 child death from accidental exposure, and the authors call for regulation to protect young people.

Walley SC, Jenssen BP, Section on Tobacco Control (2015). Electronic Nicotine Delivery Systems. Pediatrics. — PubMed PMID: 26504128 · doi:10.1542/peds.2015-3222

Liquid Nicotine Toxicity

Review, 2015. This review article looks at liquid nicotine, the concentrated nicotine solution used in e-cigarettes, and how it can poison people. The authors note that calls to poison control centers about liquid nicotine poisoning are rising, especially for children, and that e-cigarettes had no US federal regulation when the article was written. The article explains how e-cigarettes work and how nicotine acts in the body, describes current knowledge of liquid nicotine toxicity, and outlines how doctors can treat a poisoning.

Kim JW, Baum CR (2015). Liquid Nicotine Toxicity. Pediatr Emerg Care. — PubMed PMID: 26148101 · doi:10.1097/PEC.0000000000000486

The electronic cigarette: the new cigarette of the 21st century?

Review, 2014. This review describes electronic cigarettes, which are devices that deliver nicotine, and their parts. It looks at the published research on their safety, on whether they lead people to start smoking or help them quit, and on how they are regulated. The authors report that there is little data on the safety of electronic cigarettes and no evidence yet that they work as a treatment for nicotine addiction. They note that some smokers use electronic cigarettes for more than a year, often together with regular cigarettes, which keeps the nicotine addiction going, and that rising use among teenagers is a concern.

Knorst MM, Benedetto IG, Hoffmeister MC et al. (2014). The electronic cigarette: the new cigarette of the 21st century?. J Bras Pneumol. — PubMed PMID: 25410845 · doi:10.1590/s1806-37132014000500013

Nicotine replacement products: poisoning in children

Review, 2014. This article reviews poisoning in young children who swallowed or handled nicotine products, including stop-smoking aids such as gum, lozenges, patches, inhalers and mouth sprays. French poison centres recorded 318 children under 10 exposed to nicotine replacement products between 2000 and 2010; 62 of them had symptoms, and about two-thirds of those were under 4 years old. A separate U.S. analysis found 1768 poisonings involving smokeless tobacco products in children under 6 between 2006 and 2008, and 84% of those children were under 3. The first signs of nicotine poisoning are vomiting, diarrhoea, a fast heartbeat, high blood pressure and trembling hands, and higher doses can quickly lead to loss of consciousness, seizures or breathing failure. A dose of 1 mg of nicotine per kilogram of body weight can poison a child, and a dose that size is sometimes fatal in adults. Most patch poisonings happened when a child found an unused patch, a used patch thrown away carelessly, or a patch that had come off an adult's skin, so the authors say adults using these products should be warned that they are dangerous.

(2014). Nicotine replacement products: poisoning in children. Prescrire Int. — PubMed PMID: 24926513

Effects of prenatal and lactation nicotine exposure on rat testicular interstitial tissue

Animal study, 2014. This rat study gave pregnant rats nicotine (2 mg/kg/day) through a small implanted pump from the first day of pregnancy until their pups were weaned, then examined the testes and hormone levels of the male offspring at 1, 30, 60 and 90 days after birth. At 1 day old, the exposed pups had lower body weight and cholesterol, and fewer fat droplets in the testosterone-making (Leydig) cells of their testes. Nicotine exposure did not change the number of dying Leydig cells at any age. It also did not change how many Leydig cells or testicular immune cells (macrophages) there were at 60 and 90 days, but at 90 days the mature Leydig cells were enlarged and cholesterol and testosterone levels were higher. These results come from rats only.

Paccola CC, Neves FM, Cipriano I et al. (2014). Effects of prenatal and lactation nicotine exposure on rat testicular interstitial tissue. Andrology. — PubMed PMID: 24574094 · doi:10.1111/j.2047-2927.2013.00168.x

Effects of developmental nicotine exposure in rats on decision-making in adulthood

Animal study, 2012. Researchers wanted to know whether nicotine alone, rather than other parts of tobacco smoke, might cause lasting behavior changes like those seen in ADHD. Newborn male rats got nicotine (6 mg/kg/day) by stomach tube on days 1 to 7 after birth, a period meant to model the third trimester of human pregnancy. As adults, the rats were tested on risky decision-making, on waiting for a bigger reward, on working for food, and on an anxiety-related maze. Nicotine slowed the pups' weight gain while they were receiving it, but it did not change their decision-making as adults, and the only other effect was a modest drop in maze arm entries in one subgroup. The authors suggest that some of the thinking and behavior problems linked to smoking during pregnancy may come from genetic or other environmental factors, including parts of tobacco smoke other than nicotine. These results come from rats only.

Mitchell MR, Mendez IA, Vokes CM et al. (2012). Effects of developmental nicotine exposure in rats on decision-making in adulthood. Behav Pharmacol. — PubMed PMID: 22123182 · doi:10.1097/FBP.0b013e32834eb04a

The dynamic effects of nicotine on the developing brain

Review, 2009. This review looks at how nicotine affects the developing brain before birth, in early infancy and during the teenage years, using evidence from human clinical studies and from animal studies. Nicotinic receptors, which nicotine acts on, help guide brain development, and the authors report that nicotine exposure, whether from tobacco smoke or nicotine replacement therapy, interferes with this process in ways that depend on when the exposure happens. In rodents, nicotine disrupted the development of brainstem areas and chemical messenger systems before birth (equal to the first and second trimesters in humans), and changed the cortex, the hippocampus and the cerebellum shortly after birth (equal to the third trimester). During adolescence it affected the brain's emotional (limbic) system and the late maturation of its chemical messenger systems.

Dwyer JB, McQuown SC, Leslie FM (2009). The dynamic effects of nicotine on the developing brain. Pharmacol Ther. — PubMed PMID: 19268688 · doi:10.1016/j.pharmthera.2009.02.003

Maternal tobacco smoking, nicotine replacement and neurobehavioural development

Review, 2008. This review looks at how a baby's development, especially brain development and later behaviour, is affected by exposure to cigarette smoke before birth, and at nicotine replacement therapy used to help pregnant women quit smoking. The authors note that in the United States about 25% of women of childbearing age smoke, and few quit after learning they are pregnant. Nicotine replacement therapy is the most common way to quit during pregnancy, and it avoids the many other chemicals in tobacco smoke. Based on harmful effects of nicotine on brain development seen in both human and animal studies, the authors conclude that nicotine itself damages the developing nervous system and that safer ways to quit smoking during pregnancy are badly needed.

Pauly JR, Slotkin TA (2008). Maternal tobacco smoking, nicotine replacement and neurobehavioural development. Acta Paediatr. — PubMed PMID: 18554275 · doi:10.1111/j.1651-2227.2008.00852.x

Facts about nicotine toxicity

Review, 2005. This review article brings together published research on how toxic nicotine is. It covers nicotine's chemical properties, how nicotine and its breakdown product cotinine are measured, and what is known about short-term and long-term poisoning. It also looks at how the body processes nicotine, the different ways people are exposed, and the main health effects reported, especially on reproduction, the heart and blood vessels, the lungs, the digestive system, the immune system and genes. The authors focus on harmful exposure and on estimating risk.

Karaconji IB (2005). Facts about nicotine toxicity. Arh Hig Rada Toksikol. — PubMed PMID: 16370520

Smoking during pregnancy: a way to transfer the addiction to the next generation?

Review, 2002. This review looks at how smoking during pregnancy may affect children's brains and behavior later in life. It notes that studies of children whose mothers smoked while pregnant show higher risks of learning and thinking problems, attention deficit/hyperactivity disorder, conduct disorder, adult criminal behavior, and a greater tendency to start smoking and abuse alcohol. The authors explain that nicotine easily crosses the placenta, so the unborn baby is exposed to even higher nicotine levels than the mother. Because nicotinic receptors are already in the baby's brain in the first trimester and help guide brain development, the authors argue that nicotine may act directly on the developing brain for most of pregnancy.

Hellström-Lindahl E, Nordberg A (2002). Smoking during pregnancy: a way to transfer the addiction to the next generation?. Respiration. — PubMed PMID: 12169737 · doi:10.1159/000063261

The effect of nicotine on developing brain catecholamine systems

Review, 1999. This review looks at how nicotine affects the developing brain, especially the chemical messenger systems that use dopamine and norepinephrine. It reports that nicotine receptors are present early in fetal brain development. In studies where pregnant rats were given nicotine, the effects on their offspring included slowed DNA synthesis, altered brain chemistry and structure, changes in dopamine that can last into adulthood, and movement disturbances in the young animals. The effects on norepinephrine-using nerve cells are described as less clear, and the authors say more research is needed. These findings come from animal studies.

Oliff HS, Gallardo KA (1999). The effect of nicotine on developing brain catecholamine systems. Front Biosci. — PubMed PMID: 10577393 · doi:10.2741/oliff

Self-poisoning among adults using multiple transdermal nicotine patches

Human observational study, 1996. Over 24 months, 34 US poison centers reported cases of adults who put several nicotine skin patches on at the same time. There were nine cases, involving 2 to 20 patches each, and all came from intentional misuse or suicide attempts. Seven of the nine people had also taken other drugs. All nine had medical complications: seizures in 3, other changes in brain function in 8, heart and circulation effects in 6, and breathing failure in 4. Eight were hospitalized and all recovered, and blood levels of nicotine and its breakdown product cotinine did not match how sick each person was.

Woolf A, Burkhart K, Caraccio T et al. (1996). Self-poisoning among adults using multiple transdermal nicotine patches. J Toxicol Clin Toxicol. — PubMed PMID: 8941198 · doi:10.3109/15563659609013830

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PubMed Topic Searches

1. PubMed: Toxicity and Safety and nicotine (the search this page is built from)

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Connections

• Nicotine: The Research
• The Nicotine Patch, animated
• Nicotinic Acetylcholine Receptors
• Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
• Brain and Memory
• Mood and Mental Health
• Inflammation and Immunity
• Cancer Research
• Heart and Blood Vessels
• Metabolism and Weight
• Addiction and Withdrawal
• Patches, Gum and Delivery

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