WS-23 is a synthetic cooling agent, chemically known as 2-isopropyl-N,2,3-trimethylbutyramide, that produces a cold sensation on the skin and mucous membranes without any minty flavor or smell. Originally developed for food and personal care products, it has become one of the most widely used coolants in the e-cigarette industry, where it appears in the majority of flavored e-liquids sold in the United States. Its popularity has outpaced the safety research available for inhaled exposure, and recent studies raise questions about whether the quantities people are inhaling fall within safe limits.
What WS-23 Actually Is
WS-23 belongs to a family of synthetic cooling compounds sometimes called the “WS series,” developed decades ago as alternatives to menthol. Its full chemical name is 2-isopropyl-N,2,3-trimethylbutyramide, and its structure is relatively simple compared to menthol-derived coolants like WS-3. Where WS-3 (N-ethyl-p-menthane-3-carboxamide) retains the six-membered ring found in menthol, WS-23 is an open-chain amide with no ring structure at all.1Journal of Pharmacy & Pharmaceutical Sciences. Characterization Of Selective TRPM8 Ligands And Their Structure Activity Response (S.A.R) Relationship That structural difference matters: it makes WS-23 easier and cheaper to manufacture, odorless, and essentially tasteless, which is why formulators reach for it when they want cooling without any competing flavor.
In commercial products, WS-23 is typically sold as a concentrated solution suspended in propylene glycol. E-liquid manufacturers, DIY mixers, and food companies buy it at concentrations of around 30% in propylene glycol and dilute it into their final formulations.2PubMed Central. The role of synthetic coolants, WS-3 and WS-23, in modulating E-cigarette-induced reactive oxygen species (ROS) in lung epithelial cells It also appears in chewing gum, candy, toothpaste, and topical creams, though its recent explosion in popularity is driven overwhelmingly by vaping.
How WS-23 Creates a Cooling Sensation
The cooling you feel from WS-23 is not a physical temperature change. It is a neurological trick. Your body has a cold-sensing receptor called TRPM8, a protein channel embedded in sensory nerve endings that normally opens when surrounding tissue drops below roughly 26°C. Certain chemicals can force that channel open at body temperature, making the brain interpret a perfectly warm mouth or throat as cold. Menthol does this. So does WS-23, though with some differences in how strongly it binds.
In laboratory testing on cells expressing the mouse version of TRPM8, WS-23 activated the receptor with a potency about ten times weaker than menthol. Its half-maximal activation concentration was around 44 micromolar, compared to about 4 micromolar for menthol and under 1 micromolar for icilin, the most potent known TRPM8 agonist.3PubMed Central. Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay That lower potency at the receptor level might sound like a disadvantage, but in practice it means WS-23 delivers a gentler, more gradual cooling that fades more cleanly than menthol’s sharp bite. Its lack of a hexacyclic ring structure, the feature that makes menthol and WS-3 more potent at the receptor, is precisely what gives WS-23 its milder and more flavor-neutral profile.1Journal of Pharmacy & Pharmaceutical Sciences. Characterization Of Selective TRPM8 Ligands And Their Structure Activity Response (S.A.R) Relationship
Sensory panel testing in aqueous solution ranks WS-23’s cooling intensity below WS-3 and WS-5, confirming that the receptor data translates to real-world perception.4Journal of Agricultural and Food Chemistry. Trigeminal Receptor Study of High-Intensity Cooling Agents Formulators compensate by simply using more of it, which is feasible because its lack of taste or odor means higher concentrations do not introduce off-flavors the way menthol would.
How It Compares to Menthol in E-Cigarettes
When researchers directly compared e-cigarettes flavored with WS-23 against unflavored versions and menthol-flavored versions, the results were striking. Users rated WS-23 products as smoother, cooler, less bitter, and less harsh than products with no coolant. They also liked them more and were more willing to use them again, with liking scores about six points higher and coolness ratings about 20 points higher on a standardized scale.5Tobacco Control. Effects of ‘Ice’ flavoured e-cigarettes with synthetic cooling agent WS-23 or menthol on user-reported appeal and sensory attributes Against menthol specifically, WS-23 still came out ahead on smoothness, coolness, and reduced harshness.
That last finding is especially relevant for public health. Harshness and bitterness in e-cigarettes come largely from nicotine itself, and WS-23 appears to mask those sensations effectively. When a product feels smoother, users are more tolerant of higher nicotine concentrations. The same study found that WS-23 reduced perceived harshness by about 7.6 points compared to the no-coolant condition.6PubMed Central. Effects of ‘Ice’ flavoured e-cigarettes with synthetic cooling agent WS-23 or menthol on user-reported appeal and sensory attributes Tobacco researchers worry that this sensory masking lowers the barrier to starting and sustaining nicotine use, particularly among younger users drawn to “Ice” branded products.
How Common Is It in E-Liquids
Analytical chemistry studies of the US e-cigarette market have found WS-23 in a remarkable share of products. In one analysis of popular disposable e-cigarettes, 13 out of 14 Puffbar flavor varieties contained WS-23, including products not marketed with “Ice” or cooling in their names.7Nicotine & Tobacco Research. Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment A separate study described WS-23 as present in most e-liquids marketed in the US, often at concentrations that may exceed consumer exposure safety standards designed for oral ingestion.8PubMed Central. E-cigarette synthetic cooling agent WS-23 and nicotine aerosols differentially modulate airway epithelial cell responses
This ubiquity is partly invisible to consumers. WS-23 does not appear on most e-liquid ingredient labels. Because it is tasteless and odorless, it can be added to fruit, dessert, or tobacco-flavored liquids as a background smoothing agent without the consumer knowing it is there. The “Ice” descriptor on some products indicates a deliberately heavy cooling effect, but the compound itself is far more widespread than that labeling suggests.
The Safety Gap Between Eating It and Inhaling It
WS-23 has a long history of use in food and oral care products, and its safety profile for swallowed exposure is generally considered acceptable at typical dietary levels. The problem is that existing safety data were generated for oral consumption, not inhalation. When you eat something containing WS-23, it passes through the digestive system, where the liver metabolizes it before it reaches the rest of the body. When you inhale it as an aerosol, it lands directly on the thin, delicate epithelial cells lining the airways with no first-pass metabolism in between.
Researchers have tried to assess this risk using a metric called the margin of exposure, which compares the level at which a substance causes harm in animal studies to the estimated level humans are actually exposed to. A margin below 100 is generally considered inadequate for consumer safety. In the analysis of Puffbar disposable e-cigarettes, WS-23 margins of exposure fell below 100 for 10 out of 13 flavors tested across all daily use scenarios modeled.7Nicotine & Tobacco Research. Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment In plain terms, the gap between estimated safe levels and what vapers actually inhale is uncomfortably narrow for most products on the market.
What Happens in the Lungs
Cell-culture studies provide some early clues about what WS-23 aerosol does when it contacts airway tissue. In one experiment, human airway epithelial cells exposed to aerosolized WS-23 at concentrations matching real e-cigarette use showed significant changes in immune signaling. Specifically, levels of IL-6, an inflammatory messenger that plays a key role in the lung’s first-line immune response, dropped by twofold or more compared to controls. Another marker, ICAM-1, which helps immune cells stick to and interact with airway tissue, was also suppressed.9Toxicology Reports. E-cigarette synthetic cooling agent WS-23 and nicotine aerosols differentially modulate airway epithelial cell responses
At the same time, WS-23 aerosol exposure increased expression of MUC5AC, a gene responsible for producing thick, sticky mucus. MUC5AC overproduction is a hallmark of chronic airway diseases like asthma and chronic obstructive pulmonary disease. The combination of suppressed immune signaling and ramped-up mucus production is concerning because it suggests WS-23 could simultaneously dampen the lung’s ability to fight infection while creating the physical conditions that trap pathogens.8PubMed Central. E-cigarette synthetic cooling agent WS-23 and nicotine aerosols differentially modulate airway epithelial cell responses
Regarding oxidative stress, a separate study looking at reactive oxygen species found that WS-23 added to an e-liquid base (propylene glycol and vegetable glycerin) without nicotine did not significantly increase ROS levels above what the base solution alone produced. However, when both nicotine and WS-23 were present together, the combination generated more ROS than clean air controls.2PubMed Central. The role of synthetic coolants, WS-3 and WS-23, in modulating E-cigarette-induced reactive oxygen species (ROS) in lung epithelial cells That interaction is worth noting because in practice, nearly every e-liquid containing WS-23 also contains nicotine.
Early Developmental Toxicity Findings
A 2025 preprint added a different dimension to the safety picture. Researchers exposed human embryonic stem cells to WS-23 and found that even very low concentrations, in the nanomolar range, triggered calcium influx into the cells through the TRPM8 channel. Blocking the TRPM8 channel with an antagonist drug prevented the calcium influx, confirming the mechanism. The broader finding was that WS-23 disrupted normal developmental processes in these embryonic cells.10bioRxiv. A Synthetic Coolant (WS-23) in Electronic Cigarettes Disrupts Normal Development of Human Embryonic Cells
This is a single preprint using cell cultures, not a study in living organisms, so it cannot tell us whether vaping WS-23 during pregnancy would actually harm a developing fetus. But it does establish that the compound can activate its target receptor in cell types beyond sensory neurons, and at concentrations far below those used in consumer products. The researchers noted that the nanomolar sensitivity was notable because the concentrations needed were orders of magnitude lower than what appears in a typical e-liquid formulation. This study has not yet been peer-reviewed, so its conclusions should be treated with appropriate caution.
Blending WS-23 With Other Coolants
In food science and e-liquid formulation, WS-23 rarely works alone. It is frequently blended with menthol, WS-3, or other cooling agents to shape the timing and intensity of the cooling experience. Recent research using a biosensor-based approach to measure cooling intensity found that the interaction between cooling agents is not simply additive. Depending on the ratio, two coolants together can produce effects stronger or weaker than you would expect from adding their individual contributions.
For the menthol and WS-23 pair, most blending ratios produced a synergistic effect, meaning the mix delivered more cooling than the sum of its parts. Interestingly, increasing the proportion of menthol in the blend strengthened the synergy. Only at a 1:3 menthol-to-WS-23 ratio did the interaction approach a simple additive level at high effect levels.11Current Research in Food Science. Cooling sensation biosensor coupled with the Chou-Talalay method for quantitative assessment of interaction patterns in binary cooling agent mixtures The practical implication is that blending a small amount of menthol with WS-23 can amplify cooling beyond what either compound would deliver individually, allowing formulators to use less total coolant while achieving the same sensory impact.
The menthol and WS-3 pair was more complicated, with synergy at some ratios and moderate antagonism at others when the menthol fraction increased. These ratio-dependent effects mean that the specific formula matters quite a bit. Two products listing the same coolant ingredients could deliver noticeably different sensory experiences based solely on the proportions used.
Computational Toxicology and the Broader Coolant Family
WS-23 is just one of a large family of cooling agents now in commercial use. A 2025 computational screening study profiled the hazard characteristics of 178 cooling compounds across several health and environmental endpoints. The results highlight how little is known about this chemical class as a whole. Over 83% of the compounds screened were flagged as high or very high hazard for developmental toxicity, and more than half scored high for acute aquatic toxicity.12PLoS One. The tip of the iceberg: Profiling cooling agents using computational approaches to inform tobacco regulatory science
These are computational predictions, not experimental results, so they carry less certainty than a direct lab study. But they serve an important screening function: they help regulators and researchers prioritize which compounds deserve urgent experimental testing. The finding that a large majority of commercially available coolants flag for developmental toxicity in silico underscores that WS-23’s safety questions are not unique to one compound. The entire class of synthetic coolants used in consumer products sits in a grey zone where food-grade safety assessments may not translate to inhalation scenarios.
How Researchers Actually Detect and Measure WS-23
Quantifying WS-23 in e-liquids requires gas chromatography, either paired with mass spectrometry for identification or with a flame ionization detector for precise concentration measurements. Researchers use commercially available reference standards of WS-23 (at least 98% purity) to build calibration curves, then dissolve e-liquid samples in methanol with an internal standard before running them through the instrument.7Nicotine & Tobacco Research. Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment The method simultaneously detects WS-3, menthol, menthone, carvone, and nicotine, giving a comprehensive chemical snapshot of what is in a given product.
This analytical capability is relatively new in the regulatory toolkit. For years, WS-23 and WS-3 were not included in standard e-liquid testing panels, which focused on nicotine content, heavy metals, and known carbonyl byproducts like formaldehyde and acrolein. The fact that cooling agents went unmeasured for so long helps explain why their prevalence in commercial products surprised researchers when systematic surveys finally appeared. It also means that historical safety data on e-cigarette aerosol composition systematically missed one of the most common additive classes.
Why Regulation Has Not Caught Up
WS-23 exists in a regulatory gap. In food, it is generally recognized as safe for ingestion at typical dietary levels. But no regulatory body has established an inhalation safety standard for it. The US Food and Drug Administration has the authority to regulate e-cigarette ingredients, but premarket review of e-liquids has moved slowly, and synthetic coolants have not been a primary enforcement focus. Meanwhile, flavoring companies continue to sell WS-23 concentrate marketed for e-liquid use, and manufacturers add it to products at concentrations determined by sensory preference rather than any inhalation safety threshold.
The margin-of-exposure data described earlier paint a picture of a compound already being used at levels that safety pharmacologists consider potentially risky. The concentrations found in popular disposable e-cigarettes are not trace amounts; they are functional doses chosen to produce a deliberate sensory effect. And because WS-23 is not listed on most labels, consumers have no way to know whether or how much they are inhaling. For someone trying to make an informed decision about what they put in their lungs, the transparency problem is at least as significant as the toxicology problem.