Cooling Agents: WS-3, WS-23 & Novel Cooling Compounds

natural menthol is the gold standard for cooling, but it has limitations: volatility, strong mint odor, and bitterness. Synthetic cooling agents solve all three. WS-3, WS-23, and WS-5 have become essential ingredients in oral care, confectionery, pharmaceutical, and increasingly in personal care. This article covers how they work, how they differ, and what procurement managers need to know to choose the right one.

The Mechanism: How Cooling Works

All cooling agents — natural and synthetic — work through the same biological mechanism: activation of the TRPM8 ion channel, a transient receptor potential cation channel expressed in sensory neurons.

When TRPM8 is activated, it signals cold perception, even though no temperature change has occurred. This is the same receptor that menthol activates. Synthetic cooling agents are simply more selective and more potent ligands at TRPM8.

Selectivity matters. Menthol also activates TRPA1 (an irritant receptor), which is why high menthol concentrations cause a burning or stinging sensation. WS-3 and WS-23 have negligible TRPA1 activity. You get the cold without the sting.

WS-3 (N-Ethyl-p-menthane-3-carboxamide)

WS-3 was the first of the synthetic cooling agents to achieve commercial scale, developed by Wilkinson Sword (hence the "WS" prefix) in the 1970s.

Key Properties

• Molecular weight: 225.37 g/mol
• Optical rotation: racemic
• Cooling threshold: approximately 5–10 ppm in solution
• Intensity: roughly 2–3× menthol on a molar basis
• Onset: moderate (20–40 seconds)
• Duration: prolonged (30–60 minutes)
• Odor: virtually none at use levels (< 1 ppm detection threshold)
• Solubility: 0.5 g/L in water at 20 °C; soluble in ethanol, propylene glycol, caprylic/capric triglycerides

Sensory Profile

WS-3 delivers a clean, lingering cooling sensation with no bitterness and no off-flavors. The onset is not instantaneous — it builds over 20–40 seconds — but the duration is significantly longer than menthol. At high levels (above 50 ppm), a slight "cooling burn" can develop on the throat.

Applications

• Chewing gum: 50–200 ppm
• Toothpaste: 100–500 ppm
• Mouthwash: 20–100 ppm
• Confectionery: 30–150 ppm
• Topical analgesics: 500–2000 ppm
• Tobacco products: 100–500 ppm

WS-3 blends well with menthol. The combination reduces the total menthol required while providing a smoother, longer-lasting cooling effect.

Regulatory Status

• FDA: GRAS for food and confectionery applications
• EU: Approved as a flavoring substance (FL No. 16.009)
• FEMA: 4141 (approved as a flavoring agent)
• JECFA: No ADI limit specified (low toxicity)

WS-23 (2-Isopropyl-N,2,3-trimethylbutyramide)

WS-23 is the most potent of the common synthetic cooling agents and the most water-soluble.

Key Properties

• Molecular weight: 185.31 g/mol
• Cooling threshold: approximately 1–3 ppm
• Intensity: roughly 5–10× menthol on a molar basis
• Onset: fast (5–15 seconds)
• Duration: shorter than WS-3 (10–20 minutes)
• Odor: none
• Solubility: 1.0 g/L in water at 20 °C; good solubility in ethanol, PG, glycerin

Sensory Profile

WS-23 delivers immediate, intense cooling with an extremely clean profile. There is no bitterness, no medicinal note, and no burning sensation even at high levels. The cooling recedes quickly after expectoration — a property that formulators value in products where the consumer should not feel residual coldness.

Applications

• Toothpaste: 100–300 ppm
• Mouthwash: 30–80 ppm
• Chewing gum: 30–100 ppm
• Beverages: 5–30 ppm
• Pharmaceuticals: 50–200 ppm
• E-liquids / vaping: 100–500 ppm

WS-23 is heavily used in nicotine products (gum, patches, e-cigarettes) where intense, clean cooling masks the bitterness of nicotine without adding flavor notes of its own.

Regulatory Status

• FDA: GRAS for food applications
• EU: Approved flavoring (FL No. 16.101)
• FEMA: Not yet assigned (application submitted by some manufacturers)
• JECFA: Under evaluation

WS-5 (N-(4-Methoxybenzyl)-p-menthane-3-carboxamide)

WS-5 is less common than WS-3 and WS-23 but valuable for specific applications.

Key Properties

• Molecular weight: 291.43 g/mol
• Cooling threshold: approximately 0.5–1 ppm — the most potent of the three
• Intensity: roughly 10–20× menthol
• Onset: very fast (under 5 seconds)
• Duration: prolonged (45–90 minutes)
• Solubility: limited in water; requires pre-dissolution in organic solvent or oil

Sensory Profile

Extremely intense, immediate cooling with very long duration. At high levels, some consumers report a "metallic" or "chemical" off-note. WS-5 is best suited for products where cooling is the primary sensory attribute and the formulator needs maximum impact.

Applications

• Topical applications (where the prolonged duration is an advantage)
• Confectionery requiring intense cooling
• Mouth freshening strips
• High-end oral care products

Regulatory Status

• US: GRAS for limited applications
• EU: Approved as flavoring substance (FL No. 16.120)
• Less widely approved than WS-3 and WS-23. Check destination market regulations before specifying.

Additional Compounds in the Category

WS-12 (N-(4-Ethoxyphenyl)-p-menthane-3-carboxamide). Similar potency to WS-5 with a slightly cleaner profile. Growing in use in premium oral care.

Menthyl lactate (Frescolat ML). An ester of menthol and lactic acid. Delivers slow-release cooling through enzymatic hydrolysis. Used in antiperspirants and deodorants where sustained cooling is desired over 4–8 hours.

menthone glycerin acetal (Frescolat MGA). A ketal of menthone and glycerin. Provides cooling with reduced volatility. Used in applications where menthol evaporation is a problem.

Coolact 10 (isopulegol). A menthol isomer produced from citronellal. Lower cooling intensity but useful as a cost-reducing partial replacement for menthol.

Selection Decision Matrix

Selection guidance:

WS-23 is the workhorse for most applications — best balance of potency, solubility, and flavor purity. WS-3 is preferred where long duration is critical. WS-5 is for specialized products requiring maximum intensity and regulatory approval is confirmed.

Procurement Guidance

Pre-dissolution. All synthetic cooling agents are used in ppm concentrations. Pre-dissolving in ethanol, propylene glycol, or a triglyceride oil at 5–10 % ensures uniform distribution in the final product. Request the pre-dissolved form from your supplier to avoid handling errors.

Storage. Synthetic cooling agents are stable for 24+ months at room temperature. Keep sealed. WS-23 is hygroscopic — moisture absorption leads to caking.

Testing. GC-FID or GC-MS for purity. Require a chiral GC for WS-3 and WS-23 if optical purity is critical (most applications use racemic material).

Supply. India and China are the primary manufacturing locations. Indian supply is predominantly from Gujarat and Maharashtra. Chinese supply is concentrated in Zhejiang and Jiangsu. Lead time: 2–4 weeks for standard grades.

Frequently Asked Questions