Material guide: cinnamic alcohol — it cannot sensitise you; your skin turns it into something that can

For most fragrance materials, sensitising potential is a property of the molecule. Not this one.

It carries no structure capable of reacting with skin protein, so on paper it should not sensitise anyone. Yet it is a constituent of fragrance mix I, and in one Thai patch test series it took first place among 26 individual fragrance allergens.

Somebody worked out what happens in between, in 2015.

The short version

• It is the backbone of the hyacinth accord, sweet, balsamic, spicy and powdery. In our corpus it pairs with phenylacetaldehyde at a lift of 4.09, and that pair is hyacinth.
• It is a solid, pale yellow, one of the few in the starter palette. Solids handle differently from liquids.
• 371 hours on a blotter, which is long. Storage advice includes under nitrogen.
• In Vejanurug and colleagues' 2016 study it ranked first among the 26 individual allergens at 11.2%.

The basics

CAS	104-54-1
Chemical name	3-phenyl-2-propen-1-ol
Formula	C₉H₁₀O
Molecular weight	134.18
Type	Naturally occurring, also synthesised
Odour	Sweet, balsamic, hyacinth, spicy, green, powdery, cinnamyl, cinnamon, floral, fermented
Odour family	balsamic
Strength	Medium (evaluate at 10% or below)
Longevity	371 hours (blotter, neat)
Appearance	Pale yellow solid
Boiling point	250–258 °C @ 760 mmHg; 169–170 °C @ 50 mmHg
Flash point	Above 93.33 °C
logP	1.90 (est)
Natural occurrence	Ceylon cinnamon bark, cassia, star anise, storax, Peru balsam, champaca concrete 0.30%, ylang ylang oil 0.03% and others
Storage	24 months or longer; cool, dry, sealed, away from heat and light, and stored under nitrogen
Regulatory	FEMA 2294, JECFA, CoE, FLAVIS
IFRA Category 12 limit	51%
Suppliers	79
Corpus rank	26th (98 of 953 formulas, 10.3%, median dose 4.00%)

In plain terms. A logP of 1.90 is on the low side, so it tolerates water better than most fragrance materials. A boiling point above 250 °C plus a solid appearance says it is barely volatile, which is where the 371-hour blotter record comes from.

Your skin turns it into something else

Niklasson and colleagues, in Chemical Research in Toxicology in 2015, started from a contradiction.

Cinnamic alcohol is a frequent contact allergen, which is why it sits in fragrance mix I as a screening constituent. Structurally, though, it lacks a structural alert for protein reactivity — and forming a bond with skin protein is the prerequisite for sensitisation. A molecule that cannot react should not have that ability.

The answer is that it has to be activated first, either by air oxidation or by the body's own metabolism.

The authors ran incubations with human liver microsomes, modelled the possible reaction pathways with density functional theory, and then tested the reactivity of cinnamic alcohol and its metabolites against a model hexapeptide.

Alongside the known cinnamic aldehyde and cinnamic acid, the microsomal incubations produced two highly sensitising epoxides not previously observed in bioactivation studies. The authors further showed that epoxy cinnamic aldehyde forms via cinnamic aldehyde rather than via epoxy cinnamic alcohol, on two grounds: epoxy cinnamic alcohol was not depleted after its initial formation in the microsomal experiments, and the calculated activation energy for oxidising it is very high.

In plain terms: the molecule you smell is not the molecule that harms you. It gets rebuilt into something reactive after it reaches skin, or after the bottle meets air — and more than one product comes out of that rebuild.

A version of this appears in the linalool and citral oxidation storyline, but this material adds a layer: as well as air oxidation in the bottle, there is metabolic activation inside the body. Storing your bottle perfectly does not close that route.

First of the twenty-six

Vejanurug and colleagues, in Contact Dermatitis in 2016, tested 312 consecutive patients with both a baseline series and the 26 individual fragrance allergens the EU requires to be declared.

Eighty-four (26.9%) reacted, and the three most common individual allergens were:

Rank	Allergen	Positivity
1	Cinnamyl alcohol	11.2%
2	Cinnamal	9%
3	Hydroxycitronellal	3.8%

The authors note specifically that cinnamyl alcohol and cinnamal are important fragrance allergens in Thailand, and that this ranking should not be carried across to other regions. European datasets put different substances at the top.

Note the relationship between first and second place: cinnamal is one of the products of activating cinnamyl alcohol. The two correlate strongly on patch testing, which is the previous section's mechanism seen from the clinic.

The hyacinth pair

In the pairing analysis, cinnamic alcohol and phenylacetaldehyde appear together in 24 formulas at a lift of 4.09, one of the tighter pairs in the corpus.

The reason is simple: together they are hyacinth. Cinnamic alcohol supplies the sweet, balsamic, powdery body; phenylacetaldehyde supplies the sharp green and honeyed top. Neither reads as hyacinth alone, and the pair does.

It ranks 26th in the corpus at 10.3% with a median dose of 4.00% — moderately heavy, a level at which it is audible.

Handling a solid

This is the section that most needs saying in practice. Most of the starter palette is liquid; this is not, and that changes the workflow.

• Check for caking before weighing. Solids that pick up moisture or take heat form hard lumps, and digging into a lump does not weigh accurately.
• Make a 10% stock and work from that. For a solid this is close to mandatory, otherwise every formula means handling the solid again. DPG or alcohol both work; pick based on what you are building (solvents has the comparison).
• The stock is liquid but the raw material is solid, and they store differently. Neat material wants nitrogen and darkness; date the stock and refrigerate it once made.
• Weigh on a boat, not into the beaker. It sticks to glass walls, and in a small formula that loss is not negligible.

The flash point above 93 °C removes fire concerns from storage. Shelf life is 24 months or longer, but take the nitrogen line seriously — this material oxidises, and the oxidation products are precisely the more sensitising ones.

When you smell it

• Start at 10%. Neat, the powdery balsamic body dominates; dilution is what lets the green hyacinth surface.
• Build the pair with phenylacetaldehyde once. It is the cheapest hyacinth demonstration available, and clearer than any description.
• Mind its relationship to cinnamon. The name says cinnamon and there is some in the smell, but this and cinnamaldehyde are different materials with different strengths and directions. One side-by-side fixes it.
• It lasts. 371 hours means you will meet it again in the drydown, and an overdose pushes the whole thing powdery.

Buying and storage

With 79 suppliers it is easy to source. Two names coexist — cinnamic alcohol and cinnamyl alcohol — for the same material, CAS 104-54-1. For regulatory lookups use the INCI name Cinnamyl Alcohol.

It is one of the 26 fragrance substances the EU requires to be named on a cosmetic ingredient list.

Regulatory and safety

Four GHS statements: H302 harmful if swallowed, H315 causes skin irritation, H317 may cause an allergic skin reaction, H319 causes serious eye irritation.

Acute toxicity: oral rat LD50 2,000 mg/kg, guinea pig 2,675 mg/kg, dermal rabbit LD50 above 5,000 mg/kg.

IFRA carries a Standard for it, and its Category 12 limit — products with no skin contact — is 51%. Skin-contact categories sit far lower; check the current version — here is how.

Given the sensitisation mechanism, the case for gloves is stronger here than for most materials: the issue is not only the concentration in a finished product but the number of times your own hands meet the neat material.

→ Cinnamic alcohol in the database: full physical data, 79 suppliers and suggested blends. → Search by odour: try "hyacinth balsamic powdery".

References

I. B. Niklasson et al., Bioactivation of cinnamic alcohol forms several strong skin sensitizers, Chemical Research in Toxicology, 27(4), 568–575 (2015). PMID 24460212. doi:10.1021/tx400428f

P. Vejanurug et al., Fragrance allergy could be missed without patch testing with 26 individual fragrance allergens, Contact Dermatitis, 74(4), 230–235 (2016). PMID 26948414. doi:10.1111/cod.12522