Material guide: nootkatone — it smells of grapefruit, it is named after an Alaskan cypress, and it is now used to repel ticks

About a 5 minute read.

The short version

• Name: (+)-nootkatone, CAS 4674-50-4, FEMA 3166
• It is a white crystal, melting at 32–37 °C
• Odour type: citrus; odour: grapefruit peel, citrus, gardenia, woody, sweet, peely
• The taste field adds one word: bitter
• Strength medium (rank 2); substantivity 236 hours at 20% in DPG
• Suppliers: 104; oral LD50 in rat > 8000 mg/kg
• Named after a cypress; now registered as a tick repellent

The name comes from a tree in Alaska

It smells of grapefruit, but the name has nothing to do with citrus.

It comes from Callitropsis nootkatensis, the Alaska yellow cedar. Meng and colleagues' 2020 methods name it directly: "(+)-valencene synthase CnVS of Callitropsis nootkatensis."

A molecule named after a cypress is the lead in grapefruit's smell.

And the occurrence field gives actual contents, which is unusual for that field:

Source	Content
Grapefruit oil c.p. Italy	0.54%
Grapefruit oil c.p.	0.26% / 0.13% / 0.07%
Blood orange oil Italy	0.014–0.036%
Bergamot oil	0.010–0.095%

Under one name, "grapefruit oil", nootkatone content runs from 0.07% to 0.54% — nearly eightfold. I measured how one name can hold many products in a FEMA number is not an identifier; this field makes the same point with numbers.

Why its substantivity is stated at 20%

odor_substantivity: 236 hours at 20.00% in dipropylene glycol.

Because it is a white crystal (melting at 32–37 °C) — there is no neat material to put on a blotter.

Last time I counted these across the database: 165 records are not measured neat, and the 20% tier is 84.3% solids and resins while only 13.3% sit at the top strength rank. Nootkatone is the archetype — it is diluted not because it is strong (it is only rank 2) but because it is a crystal.

Its current headline is tick repellency

What Siegel and colleagues measured in Insects in 2023, across three North American human-biting tick species:

Nootkatone, a naturally occurring sesquiterpene found in the Alaskan cedar tree, grapefruit, and other sources, has been documented to be a potent acaricide.

They used a vertical filter paper bioassay, and the spread in the results is striking:

Tick species	EC50 (median effective repellent concentration)
Ixodes scapularis	0.87 ± 0.05 µg/cm²
Dermacentor variabilis	252 ± 12 µg/cm²
Amblyomma americanum	(higher still)

A 290-fold gap between the most and the next-most susceptible species.

And the most susceptible one is the principal Lyme disease vector.

(Note: this is an in vitro filter paper assay, not a test on skin. An EC50 is the concentration that repels half the individuals, which is a different thing from a usable product formulation.)

Two fields on one record contradict each other

Tucked into odor_descriptions:

characteristic grapefruit, citrus. This material is NOT to be used as a fragrance ingredient.

And the same record's cosmetic_uses field:

perfuming agents

One record, two fields, opposite instructions.

My guess is that the prohibition is one supplier's note about one grade (the evaluation field is stitched together from several sources), while cosmetic_uses is a regulatory database's classification. But the field does not tell you which applies to the bottle in front of you.

This is another instance of what I concluded in the storage field article: these fields arrive with their own sources, not from one person filling them consistently. When two disagree, ask where each came from first.

How it is made now

Meng and colleagues open their 2020 Microbial Cell Factories paper with the state of play:

The high commercial demand of (+)-nootkatone is predominately met by chemical synthesis, which entails the use of environmentally harmful reagents. Efficient synthesis of (+)-nootkatone via biotechnological approaches is thus urgently needed.

Their route is de novo synthesis in baker's yeast: use CnVS — that Alaskan cypress's valencene synthase — with mevalonate pathway engineering to make the precursor (+)-valencene in quantity, then oxidise it.

Extracting it from grapefruit peel does not pay — as the table above says, the best grapefruit oil is 0.54%. So it is either chemical synthesis or yeast.

How to use it

• It is the backbone of grapefruit, with woody and gardenia facets — an uncommon combination inside citrus.
• On the palate it brings bitterness. The field's own words are "citrus bitterness associated with grapefruit," evaluated at 20 ppm.
• It is a crystal, so a solution is more practical, and the substantivity figure was measured at 20% anyway.
• Only rank 2 in strength — it does not need the caution a sulfur compound does.
• Oral LD50 > 8000 mg/kg; acute toxicity is very low.
• Mind that "NOT to be used as a fragrance ingredient" line. Ask your supplier which regime applies to the grade you are buying.

What this doesn't establish

• I have not smelled it. This is fields, whole-database statistics, and two papers.
• Neither paper is fragrance research — Siegel is medical entomology, Meng is metabolic engineering. I cite their account of this molecule's activity and how it is produced.
• Siegel 2023 is an in vitro filter paper assay; its EC50 values do not map directly onto repellency on skin or onto any product's use level.
• I could not trace the source of the "NOT to be used" line. The evaluation field is stitched from several sources and does not label them.
• I did not check the primary literature behind the occurrence percentages, nor do I know when or by what method they were measured.
• I have not quoted the yeast production yield, because the abstract's figures are truncated.
• I checked no IFRA or US EPA text ("registered as a tick repellent" is industry common knowledge, not something established here).