Globalide® – The Musk That Never Existed in Nature
Globalide® – The Musk That Never Existed in Nature
Exaltolide, muscone, civetone – the early macrocyclic musks all came from nature, isolated from angelica root, the musk gland or the civet. Globalide® is different: according to the manufacturer, it does not occur in nature. A pure laboratory product, then – with a trademark application from 1996, two contradictory measured values in manufacturer data and the specialist literature, and a patent that is not what it first appears to be.
Contents
- A molecule with no model in nature
- A trademark from 1996
- Two sources, two values
- A patent from 2014 – but not for the invention
- What the independent safety assessment shows
- Relationship with Habanolide
- Frequently asked questions
1. A Molecule With No Model in Nature
Symrise's product information on Globalide states explicitly: "does not occur in nature" – unlike the first-generation musk classics, the molecule has no natural model. Chemically it is an oxacyclohexadecen-2-one (CAS 34902-57-3 and 111879-80-2, molecular formula C15H26O2), produced as an isomer mixture with a GC purity of at least 90%.
The brand name goes back to Haarmann & Reimer, one of the two founding houses of today's Symrise group. Haarmann & Reimer was founded in Holzminden in 1874 and pioneered the synthetic production of vanillin; Dragoco, the second founding house, was established in 1919 by Carl-Wilhelm Gerberding and August Bellmer. The two companies merged in 2003 to form the Symrise group, which thereby became the fourth-largest company in the global fragrance and flavour industry. The Globalide® trademark dates from before this merger – filed by Haarmann & Reimer, today owned by Symrise AG.
2. A Trademark From 1996
The history can be traced concretely in the US trademark register: the word mark GLOBALIDE was filed by Haarmann & Reimer GmbH on 23 August 1996 under serial number 75155043 and registered on 29 December 1998 under registration number 2215051, for "chemical preparations, namely, artificial scented substances for use in all perfumery applications". The owner today is Symrise AG; according to the register extract, the mark was last renewed on 12 October 2018.
This means that around a decade lies between the application (1996) and the merger into Symrise (2003) – Globalide is older than the corporate name under which it is sold today. None of the sources consulted gives an exact date of discovery or development for the molecule itself; the 1996 trademark application is the only concretely documented date.
3. Two Sources, Two Values
Anyone comparing Globalide data from two sources will find noticeable discrepancies. Symrise's own product information gives a partition coefficient log P (Kow) of 4.88 and a boiling point of 366 °C. The independent safety assessment by the Research Institute for Fragrance Materials (RIFM) – published in Food and Chemical Toxicology, vol. 164, article 113088, 2022 (first author A. M. Api, DOI 10.1016/j.fct.2022.113088) – arrives at a considerably higher value: log P >6.2 (measured experimentally) or 6.15 (calculated, EPI Suite model), and a lower boiling point of 333 °C at 1013 hPa.
The difference in the partition coefficient is a good 1.3 log units, in the boiling point around 33 °C. No explanation going beyond different measurement methods or model assumptions could be found in the sources consulted. The parallel with Habanolide is striking: exactly the same combination – manufacturer data versus independent measurement, with a discrepancy of similar magnitude – has already been documented there.
4. A Patent From 2014 – But Not for the Invention
A substance patent that would specifically cover the invention of oxacyclohexadecen-2-one (CAS 34902-57-3) could not be found in this research. What can be found instead is a much more recent patent: WO2016005361A1 (Symrise AG), filed on 7 July 2015 with a priority date of 7 July 2014, published on 14 January 2016, entitled "Isomer mixtures of unsaturated macrocyclic musk compounds".
This patent does not protect the molecule as such, but specific isomer mixtures with a defined mixing ratio (E-isomer to Z-isomer from 10:90 to 65:30, preferably 60:40) for a total of four related macrocyclic musks: Globanone/Aurelione (CAS 3100-36-5 / 88642-03-9), Globalide/Habanolide (CAS 34902-57-3 / 111879-80-2), Ambrettolide (CAS 28645-51-4) and Velvione (CAS 37609-25-9) – for the targeted masking of unpleasant odours and the enhancement of pleasant scent impressions in perfumed products.
The patent therefore comes almost two decades after the 1996 trademark application and protects a specific formulation application, not the original invention of the molecule. For Globalide, this suggests that the raw material itself is protected primarily through its trademark and manufacturing know-how – unlike Habanolide, whose use as an odorant Firmenich patented in 1989 with EP 0 424 787.
5. What the Independent Safety Assessment Shows
The RIFM assessment mentioned above (Food and Chemical Toxicology, vol. 164, 2022) provides a detailed picture. For repeated exposure, a NOAEL of 1000 mg/kg/day was determined (margin of exposure: 35,714), likewise for developmental and fertility toxicity (NOAEL 1000 mg/kg/day each). For skin sensitisation, the NESIL (No Expected Sensitization Induction Level) is 7500 μg/cm², with weak sensitisation potency in the animal model. Genotoxicity tests (Ames test and chromosome aberration test) were negative. The Cramer classification places the material in Class I (low toxicological potential).
The ecotoxicological picture is as follows: acute toxicity to rainbow trout LC50 = 2.0 mg/L (96 h), to Daphnia magna EC50 = 0.48 mg/L (48 h acute) and NOEC = 0.039 mg/L (21 days chronic), to Pimephales promelas NOEC = 0.027 mg/L (33 days, early life stage), to algae (Scenedesmus subspicatus) NOEC = 0.625 mg/L (72 h). The PNEC (Predicted No Effect Concentration) derived from this is 2.7 μg/L.
As regards biodegradability, several OECD studies confirm good degradation: 95–97% after 28 days (OECD 301F), 86.1–87.1% after 28 days (OECD 301B), 92% after 28 days (OECD 301C) and 95% elimination in the activated sludge test – consistent with the value of 97.0% stated by Symrise. The calculated bioaccumulation potential (screening-level BCF = 5338 L/kg, not measured directly), combined with the good degradability, does not lead to a PBT/vPvB classification under IFRA criteria. The PEC/PNEC risk ratio is below 1 for both North America and Europe – with an estimated industry volume of more than 1000 tonnes per year and a 95th-percentile concentration of 1.5% in fine fragrance, RIFM expects no environmental risk under the reported use pattern.
The fact that Globalide is nevertheless classified as hazardous to the aquatic environment with GHS09 and the H statements H400/H410 (see product page) is due to the formal GHS system: acute aquatic toxicity alone triggers the strict "Aquatic Acute 1" classification, regardless of the fact that, according to the independent assessment, biodegradation, risk quotient and exposure data indicate no real environmental risk under the described use – exactly the same pattern as with Habanolide.
6. Relationship With Habanolide
In the cited RIFM assessment, the entry is titled "Oxacyclohexadecen-2-one, CAS Registry Number 34902-57-3" – so the CAS number of Globalide appears in the title of the assessment, while Habanolide (CAS 111879-80-2) is explicitly included in it as an isomer. From the perspective of this independent source, Globalide is thus, in a sense, the "parent entry" to which Habanolide is added as a close isomer – the reverse of the common perception, in which Habanolide is often regarded as the better-known molecule.
We have already covered the isomer relationship in detail – the same molecular formula C15H26O2, a different position and geometry of the double bond, two independently registered trademarks for structurally very closely related materials – in our Habanolide article.
Frequently Asked Questions
Does Globalide occur in nature?
No. Unlike early musks such as Exaltolide, muscone or civetone, which were isolated from natural sources, Globalide is, according to the manufacturer, a purely synthetic molecule that does not occur in nature.
When was the Globalide trademark registered?
The word mark was filed by Haarmann & Reimer GmbH on 23 August 1996 (US serial number 75155043) and registered on 29 December 1998 (registration number 2215051). The exact development date of the molecule itself is not publicly documented.
Is there a patent on Globalide?
No substance patent for the molecule itself was found in this research. There is a later patent (WO2016005361A1, Symrise AG, 2014/2016), but it protects specific isomer mixtures of several macrocyclic musks – not the original invention of Globalide.
How safe is Globalide according to the independent assessment?
The RIFM safety assessment considers the material safe for the described use: high NOAEL values (1000 mg/kg/day), no genotoxicity, weak skin sensitisation potency and a PEC/PNEC risk quotient below 1 in North America and Europe. The aquatic GHS classification (H400/H410) is based on acute toxicity to aquatic organisms and does not contradict this.
What is the difference from Habanolide?
Both are isomers with the molecular formula C15H26O2 that differ in the position and geometry of the double bond. Interestingly, in the independent RIFM assessment Globalide (CAS 34902-57-3) is the title parent entry and Habanolide (CAS 111879-80-2) the included isomer. More on this in our Habanolide article.