Cooling Agent Hierarchy: When to Use WS-3, WS-5, or WS-23 in Advanced E-Liquid Formulation

Author: R&D Team, CUIGUAI Flavoring

Published by: Guangdong Unique Flavor Co., Ltd.

Last Updated:  Jan 10, 2026

Cooling Agent Receptor Nodes Illustration

Introduction: The Evolution of “Ice” in the Vaping Industry

In the nascent stages of the vaping industry, the concept of “cooling” was monolithic. It began and ended with Menthol (Mentha arvensis or synthetic l-Menthol). For decades, menthol had been the standard additive in combustible tobacco products, prized for its ability to anesthetize the throat and mask the harshness of smoke. Naturally, it migrated into early e-liquids. However, as the industry evolved from simple “cig-a-likes” to complex open-system modifications, and finally to the high-wattage sub-ohm devices and high-nicotine disposable pods of today, the limitations of menthol became glaringly apparent.

Menthol is not merely a cooling agent; it is a flavor. It possesses a distinct, potent, minty, terpene-rich, and slightly camphorous profile. While this works beautifully for mint, tobacco, and certain candy flavors, it is a formulation nightmare for delicate profiles. Try to create a realistic “Strawberry Cheesecake” or a “Warm Vanilla Custard” using menthol to provide a cooling effect, and you will inevitably destroy the flavor profile. The minty notes clash with the bakery elements, creating a dissonant sensory experience that consumers reject.

This limitation birthed the demand for “stealth cooling”—agents that could trigger the physiological sensation of cold without imparting a characteristic odor or flavor. Enter the WS series of amides. Originally developed by Wilkinson Sword in the 1970s for use in shaving foams to provide a cooling sensation without the strong odor of mint, these compounds—specifically WS-3, WS-5, and WS-23—have become the backbone of the modern “Ice” category in vaping.

Today, the “Ice” market segment is arguably the largest in the global vaping industry, particularly within the disposable pod sector. However, the prevalence of these agents has led to a commoditization of their use. Many formulators treat them as interchangeable white powders, leading to products that are either painfully cold, chemically bitter, or prone to crystallization.

As a manufacturer of specialized flavorings, we believe that distinguishing between a “good” vape and a “premium” vape often comes down to the thermal engineering of the liquid. This article serves as a definitive technical guide to the “Big Three” cooling agents, exploring their chemical structures, physiological mechanisms, and best-use scenarios to help you master the hierarchy of cold.

Section 1: The Physiology of Chill – Understanding TRPM8

To understand how to use these chemicals, one must first understand how the human body perceives “cold.” Interestingly, the sensation of cold induced by these agents is an illusion. The tissue temperature does not actually drop. Instead, these molecules interact with a specific ion channel in the sensory neurons known as TRPM8 (Transient Receptor Potential Melastatin 8).

The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. Under normal physiological conditions, TRPM8 is activated when ambient temperatures drop below approximately 26°C (78.8°F). When activated, the channel opens, allowing an influx of Calcium (Ca2+) and Sodium (Na+) ions into the nerve cell. This depolarization triggers an action potential—a signal sent to the brain that is interpreted as “cold.”

Cooling agents like Menthol and the WS series act as agonists for this receptor. They bind to the TRPM8 channel and lower the voltage threshold required for activation. Essentially, they trick the nerve into firing at body temperature (37°C), sending a “cold” signal to the brain even though the tissue remains warm.

The critical distinction for formulators is that TRPM8 receptors are not distributed evenly throughout the oral and respiratory cavities. Their density varies across the tongue, the hard and soft palate, the pharynx, and the upper esophagus. Furthermore, different cooling agents have different binding affinities and lipophilicity (fat solubility), which determines where they travel before they bind and how long they stay there.

• WS-23is highly hydrophilic (relatively speaking) and binds quickly to receptors on the anterior (front) tongue.
• WS-3is more lipophilic, allowing it to bypass early receptors and lodge deeper in the mucosa of the throat.
• WS-5binds with extreme high affinity, saturating receptors in the palate and throat for a high-intensity effect.

Understanding this “receptor mapping” is the key to creating a full-spectrum cooling experience.

Citation 1: The mechanism of TRPM8 activation by cooling agents is extensively detailed in research published by the National Center for Biotechnology Information (NCBI), specifically in studies regarding “TRP Channels and Thermosensation,” which elucidate how agonists like menthol and icilin modulate voltage-dependent gating.

Section 2: Detailed Profile – WS-23 (The Modern Standard)

Chemical Name: N,2,3-Trimethyl-2-isopropylbutanamide CAS Number: 51115-67-4 FEMA Number: 3804 Appearance: White crystalline powder Melting Point: 60-63°C

WS-23 is currently the undisputed king of the vaping market, particularly in the fruit and beverage categories. Unlike WS-3 and WS-5, which are structurally derived from menthol (possessing the p-menthane ring), WS-23 has an aliphatic structure (an open chain). This structural difference is profound: it completely eliminates the “mentholic” character.

1. Sensory Characteristics

WS-23 is unique because its cooling sensation is predominantly felt in the front of the mouth and on the tongue. It has a rapid onset—you feel it almost immediately upon inhalation—and a relatively short decay. It leaves the palate clean. Most importantly, it has zero throat hit. It does not irritate the pharynx or cause the coughing reflex often associated with high levels of menthol or WS-3.

2. Application Strategy

Because it impacts the tongue (where taste buds are located) without irritating the throat, WS-23 is the safest bet for flavor fidelity.

• Fruit Profiles:In single-note fruit flavors like Mango, Watermelon, or Blue Razz, WS-23 is essential. It provides the sensation of the fruit coming out of a refrigerator without masking the delicate ethyl maltol or fruity ester notes.
• High-Nicotine Salts:In disposable devices with 20mg/ml to 50mg/ml nicotine, the nicotine itself provides a significant throat hit. Adding WS-3 (which also hits the throat) can make the vape unpleasantly harsh. WS-23 cools the vape down without adding to the “bite,” making high-nicotine vapor smoother and more palatable.
• Usage Rates:Standard usage ranges from 0.5% to 3.0% (of a 30% solution). In “Super Ice” disposables, levels can reach nearly 5%, though this nears the solubility limit.

3. The Solubility Caveat

WS-23 is highly soluble in ethanol and Propylene Glycol (PG), but less so in Vegetable Glycerin (VG). When formulating Max VG liquids (80%+ VG), care must be taken to pre-dissolve the WS-23 in PG. If added directly to a high-VG base as a powder, it will likely fail to dissolve or will precipitate (crystallize) out of solution when the bottle is subjected to cold temperatures during shipping, leading to “shards” in the liquid.

WS-23 vs. WS-3 Material Comparison

Section 3: Detailed Profile – WS-3 (The Throat Hit Specialist)

Chemical Name: N-Ethyl-p-menthane-3-carboxamide CAS Number: 39711-79-0 FEMA Number: 3455 Trade Name: Koolada Appearance: White crystalline powder Melting Point: 88°C

Before WS-23 took over, WS-3 (Koolada) was the industry standard. It is a derivative of menthol, created by modifying the menthol molecule to remove the hydroxyl group. This removes the mint odor but retains the p-menthane ring structure, which dictates its binding behavior.

1. Sensory Characteristics

WS-3 is defined by its location. It bypasses the tongue and hits the back of the throat (pharynx). The sensation is often described as a “kick” or a “bite.” It mimics the harshness of cold alcohol or the bite of a carbonated beverage. It has a slower onset than WS-23; you often don’t feel it until the exhale or even a few seconds after the exhale.

2. Application Strategy

While less popular now as a standalone agent, WS-3 remains vital for complex formulations.

• Beverage Profiles:If you are creating a “Cola,” “Lemonade,” or “Cocktail” flavor, WS-23 is not enough. Beverages have a physical “bite” from carbonation or acidity. WS-3 simulates this bite in the throat. A Cola flavor with only WS-23 feels “flat.” A Cola flavor with a touch of WS-3 feels “fizzy.”
• Tobacco Menthol:For users transitioning from combustible menthol cigarettes, WS-23 is often “too smooth.” They miss the grab in the throat. WS-3, blended with traditional tobacco flavorings, provides that necessary respiratory impact.
• Usage Rates:WS-3 is potent and unforgiving. The typical range is 0.5% to 1.5%. Exceeding 2% often leads to a distinct chemical, plastic-like off-note and can cause significant muting of other flavors.

Section 4: Detailed Profile – WS-5 (The Heavy Artillery)

Chemical Name: N-(Ethoxycarbonylmethyl)-3-p-menthanecarboxamide CAS Number: 68489-14-5 FEMA Number: 4309 Appearance: White crystalline powder or solid Melting Point: ~80-82°C

WS-5 is the “nuclear option” of cooling agents. Structurally similar to WS-3 but with an added ethoxycarbonylmethyl group, it was chemically designed to have a higher binding affinity to TRPM8. Historically, it was shelved in the 70s due to aftertaste concerns, but modern synthesis has improved its purity profile significantly.

1. Sensory Characteristics

WS-5 is estimated to be two to three times stronger than WS-3 in terms of cooling intensity. Its primary sensation zone is the roof of the mouth (soft palate) and the back of the tongue, eventually washing down into the throat. It is responsible for the “brain freeze” sensation. The onset is instantaneous and the effect is incredibly lingering—users may still feel the cold 5 to 10 minutes after vaping.

2. Application Strategy

WS-5 is rarely used as a single agent because it is easily overwhelming.

• The “Booster” Role:WS-5 is best utilized as a spike. If you have a formulation using WS-23 that feels “cold but thin,” adding a trace amount of WS-5 (0.1% – 0.5%) adds “weight” and density to the cooling sensation without requiring you to double the total percentage of cooling agents.
• Extreme Ice Lines:For specific market segments (like the Southeast Asian market) that demand “freezing” levels of cold, WS-5 is the only way to achieve those levels without causing the solubility issues associated with massive amounts of WS-23.

Section 5: The Art of Stacking – Synergistic Formulation

The most common mistake new formulators make is relying on a single agent. To achieve a “3-Dimensional” cooling effect that feels natural and immersive, one must employ Synergistic Stacking. This involves combining agents to target multiple receptor sites simultaneously.

1. The “Halo Effect”

By stimulating the tongue (WS-23), the roof of the mouth (WS-5), and the throat (WS-3), you create a “halo” of cold that surrounds the user’s sensory perception.

2. Recommended Stacking Ratios (The “Golden Triad”):

l The “All-Day Vape” (ADV) Fruit Blend:

• Goal:Refreshing, fruity, smooth, low fatigue.
• Ratio:80% WS-23 / 20% WS-3.
• Total Concentration:5% in final mix.
• Why:The WS-23 carries the fruit flavor on the tongue. The small amount of WS-3 adds a slight refreshing crispness to the exhale without irritating the throat.

l The “Ice Blast” / Disposable Style:

• Goal:Maximum impact, instant freeze, masking nicotine.
• Ratio:60% WS-23 / 30% WS-5 / 10% WS-3.
• Total Concentration:0% – 4.0% in final mix.
• Why:WS-23 hits first. WS-5 creates the booming intensity in the middle. The trace of WS-3 ensures the cold is felt deep in the lungs.

l The “Soda/Fizz” Simulation:

• Goal:Texture and bite.
• Ratio:50% WS-23 / 50% WS-3.
• Total Concentration:0% – 2.0% in final mix.
• Why:The high ratio of WS-3 creates the “prickle” associated with carbonation bubbles bursting in the throat.

Section 6: Technical Challenges – Solubility, Crystallization, and Muting

Formulating with high levels of cooling agents introduces distinct physical chemistry challenges that can lead to product recalls if not managed.

1. Crystallization (Recrystallization)

Cooling agents are solids at room temperature. They are dissolved into the e-liquid carrier (PG/VG). If the concentration of the solid exceeds the saturation point of the solvent system, the cooling agent will precipitate back into solid form. This looks like broken glass shards floating in the e-liquid or settling at the bottom of the pod.

• The Risk Factor:VG is a poor solvent for these amides. The higher the VG content (e.g., 70/30 or 80/20 mixes), the less cooling agent the liquid can hold.
• The Solution:Do not exceed 3.5% total cooling agent load in High-VG liquids. Always pre-dissolve crystals in pure PG with mild heat (40°C) before adding to the main batch. If using pre-diluted solutions (usually 30% concentration), ensure they are shaken before dispensing.

2. Flavor Muting

This is a biological, not chemical, phenomenon. Extreme cold causes vasoconstriction (narrowing of blood vessels) in the mouth and desensitizes the taste buds. Furthermore, the brain prioritizes the strong “cold” signal over delicate flavor signals.

• The “Cream” Problem:Custards, vanillas, and dairy notes are the first to disappear under heavy cooling. The complex volatiles that make up a “bakery” profile are easily masked.
• The Solution:When formulating “Ice Creams,” use WS-23 exclusively and at low levels (<1.0%). Avoid WS-3 entirely, as its chemical taste clashes with dairy. You may need to over-flavor the base concentrate by 15-20% to compensate for the muting effect of the coolant.

3. Equipment Contamination

WS-5 and WS-3 are incredibly persistent. They adhere to stainless steel and silicone gaskets in mixing tanks.

The Solution:Dedicate specific tanks and hoses for “Ice” products. If sharing equipment, a standard hot water wash is insufficient. You must use an ethanol flush or a specialized surfactant cleaning cycle to remove the lipophilic residues of the cooling agents, otherwise, your next batch of “Warm Tobacco” will have an inexplicable ghostly cooling effect.

Cooling Agent Comparison Infographic

Section 7: Regulatory Landscape and Safety Considerations

In the current climate of heightened scrutiny on vaping products, manufacturers must be rigorous regarding compliance and safety.

1. FEMA GRAS Status

The Flavor and Extract Manufacturers Association (FEMA) has evaluated these substances. WS-3 (FEMA 3455), WS-23 (FEMA 3804), and WS-5 (FEMA 4309) are all designated as GRAS (Generally Recognized As Safe). This designation, however, is primarily based on ingestion (food/drink).

Citation 2: The Flavor and Extract Manufacturers Association (FEMA) maintains a definitive list of GRAS flavoring substances. Their expert panel reviews scientific data to ensure safety for intended use in food, which serves as the baseline for raw material purity in the vaping supply chain.

2. Inhalation Toxicology

While GRAS for food is a starting point, inhalation is physiologically distinct. The lungs lack the robust metabolic protections of the gut.

• Recent Studies:A 2021 study highlighted in Tobacco Control analyzed the transfer rates of synthetic coolants in Juul-compatible pods, noting that while ubiquitous, the concentrations in aerosols generally matched the e-liquid, implying stable transfer without thermal degradation into toxic byproducts (like aldehydes) under normal vaping conditions.
• BfR Position:The German Federal Institute for Risk Assessment (BfR) has noted the lack of long-term inhalation data for these specific compounds, urging manufacturers to adhere to the precautionary principle and avoid excessive dosing.

Citation 3: A study published in Tobacco Control (BMJ Journals) titled “Synthetic cooling agents in US-marketed e-cigarette refill liquids” provides quantitative analysis on the prevalence and concentrations of WS-3 and WS-23, offering benchmarks for standard industry usage rates.

Citation 4: The German Federal Institute for Risk Assessment (BfR) has issued opinions (e.g., Opinion No 015/2023) regarding the assessment of additives in e-cigarettes, highlighting the need for toxicological data on flavor compounds including cooling agents.

For the manufacturer, this means transparency is key. We recommend:

• Purity Testing:Sourcing agents with >99.5% purity to avoid synthesis byproducts.
• Safety Data Sheets (SDS):Maintaining strict SDS libraries for every batch.
• TPD Compliance:In the EU, all ingredients including cooling agents must be declared in the TPD submission. Ensuring your specific CAS numbers match the approved list is vital for market entry.

Section 8: The Future of Cooling – Beyond the Big Three

The industry is not static. As consumers build tolerance to WS-23, flavor houses are researching the next generation of cooling.

• WS-12:A potential successor to WS-3. It activates TRPM8 but has a significantly longer duration and a “milder” initial impact, making it interesting for therapeutic or “slow-release” applications.
• Hybrid Molecules:Research is ongoing into modifying the amide structure to increase solubility in VG, which would solve the crystallization issues inherent in current high-power formulations.
• Natural Extraction:There is a niche but growing demand for “All Natural” e-liquids. While synthetic WS agents are “nature-identical” or derivatives, some brands are exploring fractionated distillates of mint that remove the flavor volatiles while keeping the cooling precursors, though this remains less effective than the pure WS series.

Conclusion: Engineering the Perfect Chill

The era of dumping a random scoop of “Ice Powder” into a mixing vat is over. The modern consumer is sophisticated; they can tell the difference between a cheap, throat-scratching coolant and a premium, smooth, expertly layered cooling profile.

Flavor manufacturing is a discipline that sits at the intersection of art and chemical engineering. By understanding the distinct hierarchy of WS-23, WS-3, and WS-5, you gain control over the sensory experience. You can craft a beverage that fizzes, a fruit that refreshes, or a menthol that satisfies, all by pulling the right levers on the TRPM8 receptor.

At [Your Company Name], we do not just sell powder; we sell solutions. We understand the delicate balance of solubility, sensory mapping, and shelf stability. Whether you are battling crystallization in a new disposable line or trying to fix a muted custard, the answer lies in the chemistry.

Premium Cooling Agent Product Lineup

Call to Action: Upgrade Your Formulation Strategy today

Are you struggling with recrystallization issues in your high-VG lines? Is your current cooling blend muting your top notes? Or are you simply looking for a more reliable, high-purity source for WS agents?

Our technical team is ready to assist you in optimizing your cooling hierarchy. We offer pre-solvated cooling bases, raw high-purity crystals, and custom formulation consulting.

Connect with our Flavor Chemists:

Request a “Cooling Discovery Kit” (Samples of WS-23, 3, & 5):