Think electronic cigarettes without nicotine are harmless? Think again. A new study shows that the flavorings in e-cigs can harm human infection-fighting cells.
E-cigarettes work by heating a flavored liquid to make a mist that users inhale, or “vape.” These flavored liquids, called e-liquids, usually contain nicotine. But not always. Manufacturers add nicotine for vapers who want a buzz from their e-cigarettes. It’s the same stimulant that true cigarettes deliver. That nicotine — made from tobacco — qualifies most e-cigs as “tobacco products.”
The nicotine may be useful for adults who are addicted to cigarettes and want to wean themselves off. But nicotine can harm children and teens. That’s why some young people may choose to vape instead of smoke, and use nicotine-free products. But the new data suggest that e-cigs can still be toxic, even without nicotine.
“We know these flavors are really attractive to teens,” says Irfan Rahman. He works at the University of Rochester in New York. He says studies have shown that one reason many teens try e-cigarettes is an interest in fruity and candy-flavored products.
As a toxicologist, Rahman studies whether various materials can poison the body’s cells or tissues. His team decided to test whether certain flavored e-liquids are toxic (meaning poisonous). They tested several common e-liquid flavorings. These included cinnamon roll, cotton candy, melon, pineapple, coconut and cherry.
Such flavorings are considered safe in foods. That’s because after a person swallows them, they’re broken down in the gut. But that doesn’t mean these same chemicals are safe to breathe in. They could harm parts of the respiratory tract, such as the lungs.
Rahman’s team didn’t expose people to these flavorings, in case they were harmful. Instead, they tested e-liquid chemicals on human cells in a dish. This helped them judge whether the chemicals might also harm cells inside the body.
The answer: Some of the vaped flavorings did prove toxic to those cells. The researchers published their findings in the January Frontiers in Physiology.
Cells vs. cinnamon
After a person vapes, e-liquid chemicals could pass through the walls of small vessels in the lungs to enter the blood, says Thivanka Muthumalage. He’s a researcher in Rahman’s lab.
Rahman’s team wanted to know what would happen when these chemicals encountered blood cells. In one set of tests, the researchers exposed blood cells directly to the flavorings. They chose a type of white blood cell called a macrophage (MAK-roh-fayj). These cells are part of the immune system, which fights disease. Macrophages hunt down and “eat” particles that shouldn’t be in the blood stream. Those foreign particles could be germs or other things that might make people sick.
The team used doses of flavoring chemicals similar to what are in the e-liquids that you can buy at a store, says Muthumalage. The doses in the experiment might even have been lower than what people would vape.
To measure how toxic each chemical was, the researchers looked for signs of stress in the cells, or even cell death. A number of e-liquid flavoring chemicals caused high levels of cell stress or death. Those included flavorings that taste buttery (these contain the chemicals pentanedione and acetoin). They also included flavorings that taste like vanilla (O-vanillin), cotton candy, caramel (maltol) and cinnamon (cinnamaldehyde).
That last one, cinnamaldehyde (Sih-nuh-MAAL-duh-hide), killed the most cells. And that’s bad. Dead immune cells can’t fight infection, explains Muthumalage.
His team’s findings are backed up by a study in the March 27 PLOS Biology. Researchers at the University of North Carolina School of Medicine in Chapel Hill tested the effects of 148 e-liquids on human cells. When exposed to vapors of some e-liquid flavors, it showed, fewer of these cells grew. The worst culprits? Cinnamaldehyde and vanillin.
A vaping machine
In a second set of tests, the researchers used a “vaping machine” to suck e-liquids through an e-cigarette. Afterward, they measured what vapors had entered the air. These mists are what an e-cig user would ordinarily inhale. The researchers then exposed human cells to these vapors.
They showed that heating each flavoring in an e-cigarette created harmful levels of molecules that can damage cells. What’s more, mixing two or more flavors together caused even higher levels of these damaging molecules than did heating each on its own.
This suggests that breathing in multiple e-liquid flavors could be more dangerous than exposure to just one at a time.
That’s concerning, says Melanie Prinz. She’s a college student who worked on the study in Rahman’s lab. “Teens at parties often pass their [e-cig] devices around,” she notes. That means they could be “sharing and inhaling a lot of different flavors.”
The findings from Rahman’s lab agree with the findings from another study. It looked at vapors from nicotine-free e-cigs. Here, researchers at the University of California San Francisco studied the urine of teens who had vaped e-liquids without nicotine. The researchers looked for toxic chemicals that form when e-liquids are heated. The teens had up to three times the levels of five potentially cancer-causing chemicals in their bodies as did those who didn’t vape. These findings appear in the April Pediatrics.
That was the first study to measure the toxic chemicals that can get into the bodies of teens vaping nicotine-free e-liquids.
Cause for concern
Maciej Goniewicz works at the Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. There he, too, studies the health effects of e-cig vapors. Testing the toxicity of e-liquid flavoring on cells is extremely important, he says. It helps identify which chemicals may be “bad actors,” he explains.
If these tests show strong toxicity, they could help government agencies decide which products to regulate — or even ban. Such data, he adds, could also help manufacturers create safer vape products.
One benefit of studying cells in a dish, rather than studying actual people, is that you can limit variables, Goniewicz says. For instance, the Rochester team could omit nicotine, a known bad actor. But in real life, people might vape a liquid with nicotine one day and another without nicotine the next day. This could make it harder for scientists to tease apart the effects of flavorings and nicotine.
But cell studies are just one piece of the puzzle. They’re good for identifying potentially toxic chemicals. They don't, however, tell us about the long-term effects of exposure to them. Human studies will — but they take far longer. A disease may not show up for years or decades after a toxic exposure.
In fact, a large review found that the long-term health effects of vaping are not yet clear. A review is a research paper that gathers the results of other studies. This paper included more than 800 scientific studies — and found cause for concern.
For instance, it found “moderate evidence” that vaping led to more coughing and wheezing in teens, and worse asthma. There is also moderate evidence linking vaping to a short-term rise in blood pressure, and to harmful stiffening of blood vessels. And the review authors found “substantial evidence” that e-cig vapors can damage DNA and cells.
This massive report, released January 23, was issued by the U.S. National Academies of Sciences, Engineering and Medicine.
asthma A disease affecting the body’s airways, which are the tubes through which animals breathe. Asthma obstructs these airways through swelling, the production of too much mucus or a tightening of the tubes. As a result, the body can expand to breathe in air, but loses the ability to exhale appropriately. The most common cause of asthma is an allergy. Asthma is a leading cause of hospitalization and the top chronic disease responsible for kids missing school.
blood pressure The force exerted against vessel walls by blood moving through the body. Usually this pressure refers to blood moving specifically through the body’s arteries. That pressure allows blood to circulate to our heads and keeps the fluid moving so that it can deliver oxygen to all tissues. Blood pressure can vary based on physical activity and the body’s position. High blood pressure can put someone at risk for heart attacks or stroke. Low blood pressure may leave people dizzy, or faint, as the pressure becomes too low to supply enough blood to the brain.
blood vessel A tubular structure that carries blood through the tissues and organs.
cancer Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall.
chemical A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
chronic A condition, such as an illness (or its symptoms, including pain), that lasts for a long time.
DNA (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. It is built on a backbone of phosphorus, oxygen, and carbon atoms. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.
e-cigarette (short for electronic cigarette) Battery-powered device that disperses nicotine and other chemicals as tiny airborne particles that users can inhale. They were originally developed as a safer alternative to cigarettes that users could use as they tried to slowly break their addiction to the nicotine in tobacco products. These devices heat up a flavored liquid until it evaporates, producing vapors. People use these devices are known as vapers.
e-liquid A term for the solutions heated to the evaporation point in an electronic cigarette. These solutions are the basis of the vapors that will be inhaled. The liquid typically contains a solvent into which flavorings and nicotine have been dissolved.
flavor The particular taste associated with something that is eaten or drunk. This is based largely on how it is sensed by cells in the mouth. It can also be influenced, to some extent, by its smell.
germ Any one-celled microorganism, such as a bacterium or fungal species, or a virus particle. Some germs cause disease. Others can promote the health of more complex organisms, including birds and mammals. The health effects of most germs, however, remain unknown.
gut An informal term for the gastrointestinal tract, especially the intestines.
immune system The collection of cells and their responses that help the body fight off infections and deal with foreign substances that may provoke allergies.
infection A disease that can spread from one organism to another. It’s usually caused by some type of germ.
macrophage A type of white blood cell dispatched by the immune system. Like janitors of the body, they gobble up germs, wastes and debris for disposal. These cells also stimulate other immune cells by exposing them to small bits of the invaders.
nicotine A colorless, oily chemical produced in tobacco and certain other plants. It creates the “buzz” associated with smoking. Highly addictive, nicotine is the substance that makes it hard for smokers to give up their use of cigarettes. The chemical is also a poison, sometimes used as a pesticide to kill insects and even some invasive snakes or frogs.
oxidation (adj. oxidative) A process that involves one molecule’s theft of an electron from another. The victim of that reaction is said to have been “oxidized,” and the oxidizing agent (the thief) is “reduced.” The oxidized molecule makes itself whole again by robbing an electron from another molecule. Oxidation reactions with molecules in living cells are so violent that they can cause cell death. Oxidation often involves oxygen atoms — but not always.
particle A minute amount of something.
respiratory Of or referring to parts of the body involved in breathing (called the respiratory system). It includes the lungs, nose, sinuses, throat and other large airways.
respiratory tract Parts of the body involved in breathing (also called the respiratory system). It includes the lungs, nose, sinuses, throat and other large airways.
stimulant Something that triggers an action. (in medicine) Drugs that can stimulate the brain, triggering a feeling of more energy and alertness. Caffeine, for instance, is a mild stimulant that for a short while enhances alertness and helps fight drowsiness. Other stimulants, including some dangerous illegal drugs — such as cocaine — have stronger or longer-lasting effects.
tissue Made of cells, any of the distinct types of materials that make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues.
tobacco A plant cultivated for its leaves, which many people burn in cigars, cigarettes, and pipes. Tobacco leaves also are sometimes chewed. The main active drug in tobacco leaves is nicotine, a powerful stimulant (and poison).
toxic Poisonous or able to harm or kill cells, tissues or whole organisms. The measure of risk posed by such a poison is its toxicity.
toxicologist A scientist who investigates the potential harm posed by physical agents in the environment. These may include materials to which we may be intentionally exposed, such as chemicals, cigarette smoke and foods, or materials to which we are exposed without choice, such as air and water pollutants. Toxicologists may study the risks such exposures cause, how they produce harm or how they move throughout the environment.
tract A particular, well-defined area. It can be a patch of land, such as the area on which a house is located. Or it can be a bit of real estate in the body. For instance, important parts of an animal’s body will include its respiratory tract (lungs and airways), reproductive tract (gonads and hormone systems important to reproduction) and gastro-intestinal tract (the stomach and intestines — or organs responsible for moving food, digesting it, absorbing it and eliminating wastes).
vaping (v. to vape) A slang term for the use of e-cigarettes because these devices emit vapor, not smoke. People who do this are referred to as vapers.
vapors Fumes released when a liquid transforms to a gas, usually as a result of heating.
Journal: M.L. Rubinstein et al. Adolescent exposure to toxic volatile organic chemicals from e-cigarettes. Pediatrics. Vol. 141, April 2018, p. e20173557. doi: 10.1542/peds.2017-3557.
Journal: M.F. Sassano et al. Evaluation of e-liquid toxicity using an open-source high-throughput screening assay. PLoS Biology. Vol 16, March 27, 2018, p. e2003904. doi: 10.1371/journal.pbio.2003904.
Report: Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems. Public Health Consequences of E-Cigarettes. The National Academies of Sciences, Engineering, and Medicine. Published online January 23, 2018. doi: 10.17226/24952.
Journal: T. Muthumalage et al. Inflammatory and oxidative responses induced by exposure to commonly used e-cigarette flavoring chemicals and flavored e-liquids without nicotine. Frontiers in Physiology. Vol. 8, Article No. 1130, published online January 11, 2018. doi: 10.3389/fphys.2017.01130.