Galaxolide

Galaxolide
Names
IUPAC name
4,6,6,7,8,8-Hexamethyl-1,3,4,6,7,8-hexahydrocyclopenta[g]isochromene
Other names
Hexahydrohexamethyl cyclopentabenzopyran
HHCB
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.013.588
Properties
C18H26O
Molar mass 258.40 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Galaxolide (trade name; also known as Abbalide, Pearlide, Astrolide, Musk 50, Polarlide; chemical name 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8,-hexamethyl-cyclopenta[g]benzopyran or HHCB) is a synthetic fragrance with a clean sweet musky floral woody odor used in fragrances. It is one of the musk components that perfume and cologne manufacturers use to add a musk odor to their products. Galaxolide was first synthesized in 1965, and used in the late 1960s in some fabric softeners and detergents.[1] High concentrations were also incorporated in fine fragrances.

Chemistry

Galaxolide is the trade name from International Flavors & Fragrances Inc. (IFF) for the fragrance material with CAS Registry Number 1222-05-5 and CAS chemical name cyclopenta(g)-2-benzopyran, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-.

Galaxolide is also known by its IUPAC name 4,6,6,7,8,8-hexamethyl-1,3,4,6,7,8-hexahydro-cyclopenta[g]-isochromene and the more commonly used acronym of the chemical name 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8,-hexamethyl-cyclopenta[g]benzopyran (HHCB). The abbreviation for this chemical name, HHCB, is commonly used for galaxolide in various publications. Galaxolide may also be known as hexamethylindanopyran under the International Nomenclature of Cosmetic Ingredients (INCI).

Physical-chemical properties

Galaxolide is a mixture of isomers. It has chiral centers at carbon atom 4 and 7. The isomers are (4R,7R), (4R,7S), (4S,7S) and (4S, 7R). Galaxolide has a molecular formula of C18H26O and a molecular weight of 258.4 g/mol. At room temperature, it occurs as a highly viscous liquid. Its melting point is -20 °C and its boiling point is estimated to be 330 °C based on a boiling point of 160 °C at 4hPa.[2]

History

Galaxolide was discovered at IFF in the 1960s, by Heering and Beets.[3]

It was first synthesized in 1965 and its discovery was mainly due to the work by Beets on the osmophoric group of the polycyclic musks, where they tried to improve existing synthetic musks by making them more stable and hydrophobic [4]

Odor

Galaxolide has become the key synthetic musk ingredient belonging to the polycyclic musk group as defined by the International Fragrance Association (IFRA). Its odor is described as a “clean”, sweet, floral, woody musk,[5] Research has shown that it is in particular the (4S,7R) and the (4S, 7S) forms of galaxolide that are the most powerful musk notes, with odor thresholds of 1 ng/l or less.[6]

Environmental data

Galaxolide has a measured bioconcentration factor (BCF) in fish in a range of 600-1600 and a log octanol/water partition coefficient (Log Kow) of around 5.5 (5.3 – 5.9).[2]

Given its lack of bioaccumulation and toxicity, the EU determined that galaxolide does not meet the criteria for being a substance classified as Persistent, Bioaccumulative and Toxic to the environment (PBT).[7][8] However, the EPA's assessment of galaxolide found it to be moderately persistent and bioaccumulative and highly toxic to aquatic organisms.[9] The EPA's PBT Profiler also finds Galaxolide to exceed the EPA's criteria as a PBT.[10]

Galaxolide degrades in the environment to primary degradants with log Kow <4 and further to more hydrophilic products with Log Kow of <1.[2]

Galaxolide is classified as R50/53 under the EU DSD and as H410 under EU CLP classification rules.[2]

Although there have been reports of galaxolide in environmental compartments,[11][12][13] these studies have been made part of galaxolide’s environmental safety reviews by various authorities, who have deemed that there is no need for risk reduction measures.[7][14][15]

Galaxolide contamination has been detected in the Great Lakes. In a study of lake sediment in Lake Erie found galaxolide levels to be doubling every 8–16 years.[16] Galaxolide was detected in 92% of water samples from Lake Michigan.[17]

Galaxolide has been shown to be removed by ozonation in wastewaters treatment plants.[18]

Galaxolide has been reported to be found in human biomonitoring studies and its presence in human tissue has been evaluated by several scientific authorities. For examples, traces of galaxolide were detected in 97% of breast milk samples in mothers from Massachusetts in a 2004 study.[19]

Human health

Galaxolide is not an irritant, not toxic, not a CMR substance nor a sensitizer.[2] Based on test data, the EU Scientific Committee for Consumer Safety included galaxolide in their proposal for extending the allergen information on cosmetic products as it claims to have seen only up to 100 individual cases worldwide in the last several decades who have reported irritation or allergic reactions to galaxolide through the use of cosmetic products.[20]

Extensive investigations into the presence of galaxolide in biomonitoring studies,[13][21] have been completed and evaluated by various regulatory authorities. The outcome of all those studies is that galaxolide is safe for use in consumer products.[7][22][23]

Regulatory and safety status

In 2002, The Scientific Committee on Cosmetics and Non-Food Products (SCCNFP), the expert scientific board that advises the European Commission on human health issues, reviewed the human safety of galaxolide, when used in cosmetic products, and issued a final opinion on 17 September 2002.[22] The SCCNFP stated that "...HHCB [galaxolide] can be safely used as a fragrance ingredient in cosmetic products without any restriction for its use."

In March 2003, the European Chemicals Bureau (ECB) concluded that galaxolide is not a persistent, bioaccumulative and toxic substance (PBT) according to the ECB criteria and removed galaxolide from their draft list of PBTs.[8]

Under the EU Existing Substances Directive, galaxolide is listed in the 4th Priority List of Substances for review by the EU. This Priority List was the 4th list compiled by the EU of high volume substances that were to be evaluated by the Member States’ Competent Authorities, as part of the requirements of EU Council regulation 793/93 “On the Evaluation and Control of the risk of existing substances”. The EU published the final report for this study in 2008[7] and concluded that for all human health and environmental endpoints, "There is at present no need for further information and/or testing and no need for risk reduction measures".

Additionally the European Union Scientific Committee for Health and Environmental Risks (SCHER), an advisory body to the European Commission, independently reviewed the environmental, human health, and indirect exposure risk assessment, and agreed with all of the conclusions from the EU experts on the outcome that, "There is at present no need for further information and/or testing and no need for risk reduction measures". The SCHER opinions for galaxolide are available for the environment,[14] for human health[24] and for human health though indirect exposure.[25]

As part of the obligations under the EU’s Registration, Evaluation and Authorization of Chemicals (REACH),[26] the producers and importers of galaxolide on the EU market have registered galaxolide in December 2010[2] with the European Chemicals Agency in Helsinki.

In 2010, the state of Oregon added galaxolide to its Priority Persistent Pollutants (P3) list. This is a list of persistent, bioaccumulative toxics that have a documented effect on human health, wildlife and aquatic life.[27]

In the USA, the Environmental Protection Agency under its Toxic Substance Control Act Work Plan Chemicals Program[28] evaluated galaxolide for human health and environmental effects and concluded that "...the assessment does not indicate risk concerns".[15]

References

  1. ↑ http://www.chemicalbook.com/ChemicalProductProperty_EN_CB1706143.htm
  2. 1 2 3 4 5 6 All physical chemical data are derived from the galaxolide REACH registration dossier: http://echa.europa.eu/information-on-chemicals/registered-substances, CAS 1222-05-5
  3. ↑ Heeringa L.G. and Beets M.G.J., 1965, New Tricyclic Isochromans with Musk Odour. United Kingdom Patent: 991,146).
  4. ↑ David Rowe (2005). Chemistry and Technology of Flavours and Fragrances. p. 152. ISBN 1-4051-1450-9.
  5. ↑ "Galaxolide". PerfumersWorld.
  6. ↑ Fráter, Georg; Müller, Urs; Kraft, Philip (1999). "Preparation and Olfactory Characterization of the Enantiomerically Pure Isomers of the Perfumery Synthetic Galaxolide". Helvetica Chimica Acta. 82 (10): 1656–65. doi:10.1002/(SICI)1522-2675(19991006)82:10<1656::AID-HLCA1656>3.0.CO;2-M.
  7. 1 2 3 4 http://echa.europa.eu/documents/10162/947def3b-bbbf-473b-bc19-3bda7a8da910%5B%5D
  8. 1 2 OSPAR review of various musk ingredients: http://www.ospar.org/documents?v=6978 – page 39 and Annex 3
  9. ↑ EPA,OCSPP,OPPT,CCD, US. "TSCA Work Plan Chemical Risk Assessment HHCB 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-g-2- benzopyran". www.epa.gov. Retrieved 2016-04-26.
  10. ↑ "PBT Profiler for CAS # 1222-05-5". www.pbtprofiler.net. Retrieved 2016-04-26.
  11. ↑ Chen, Duohong; Zeng, Xiangying; Sheng, Yanqing; Bi, Xinhui; Gui, Hongyan; Sheng, Guoying; Fu, Jiamo (2007). "The concentrations and distribution of polycyclic musks in a typical cosmetic plant". Chemosphere. 66 (2): 252–8. PMID 16814843. doi:10.1016/j.chemosphere.2006.05.024.
  12. ↑ Rüdel, Heinz; Böhmer, Walter; Schröter-Kermani, Christa (2006). "Retrospective monitoring of synthetic musk compounds in aquatic biota from German rivers and coastal areas". Journal of Environmental Monitoring. 8 (8): 812–23. PMID 16896465. doi:10.1039/b602389b.
  13. 1 2 Kannan, Kurunthachalam; Reiner, Jessica L.; Yun, Se Hun; Perrotta, Emily E.; Tao, Lin; Johnson-Restrepo, Boris; Rodan, Bruce D. (2005). "Polycyclic musk compounds in higher trophic level aquatic organisms and humans from the United States". Chemosphere. 61 (5): 693–700. PMID 16219504. doi:10.1016/j.chemosphere.2005.03.041.
  14. 1 2 EU Scientific Committee on Health and Environmental Risks; Environmental Assessment of HHCB http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_096.pdf
  15. 1 2 EPA review of HHCB: https://cfpub.epa.gov/si/si_public_file_download.cfm?p_download_id=520638
  16. ↑ Peck, Aaron M.; Linebaugh, Emily K.; Hornbuckle, Keri C. (2006). "Synthetic Musk Fragrances in Lake Erie and Lake Ontario Sediment Cores". Environmental Science & Technology. 40 (18): 5629–35. PMC 2757450 Freely accessible. PMID 17007119. doi:10.1021/es060134y.
  17. ↑ Peck, Aaron M.; Hornbuckle, Keri C. (2004). "Synthetic Musk Fragrances in Lake Michigan". Environmental Science & Technology. 38 (2): 367–72. Bibcode:2004EnST...38..367P. PMID 14750709. doi:10.1021/es034769y.
  18. ↑ Ternes, Thomas A; Stüber, Jeannette; Herrmann, Nadine; McDowell, Derek; Ried, Achim; Kampmann, Martin; Teiser, Bernhard (2003). "Ozonation: a tool for removal of pharmaceuticals, contrast media and musk fragrances from wastewater?". Water Research. 37 (8): 1976–82. PMID 12697241. doi:10.1016/S0043-1354(02)00570-5.
  19. ↑ Reiner, Jessica L.; Wong, Chung M.; Arcaro, Kathleen F.; Kannan, Kurunthachalam (2007). "Synthetic Musk Fragrances in Human Milk from the United States". Environmental Science & Technology. 41 (11): 3815–20. Bibcode:2007EnST...41.3815R. PMID 17612154. doi:10.1021/es063088a.
  20. ↑ EU Scientific Committee on Consumer Safety; Opinion on Fragrance Allergens: http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_o_102.pdf, Table 7-1, page 47 and Table 13-1, page 107
  21. ↑ Rimkus, G.G. and M. Wolf, Polycyclic musk fragrances in human adipose tissue and human milk. Chemosphere, 1996, 33(10), pages 2033-2043, doi:10.1016/0045-6535(96)00321-9
  22. 1 2 EU-SCCNFP safety evaluation for HHCB in cosmetics: http://ec.europa.eu/health/ph_risk/committees/sccp/documents/out179_en.pdf
  23. ↑ EU Risk Assessment Report on HHCB: http://echa.europa.eu/documents/10162/947def3b-bbbf-473b-bc19-3bda7a8da910
  24. ↑ EU-SCHER Opinion on HHCB safety for human health http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_086.pdf
  25. ↑ EU-SCHER Opinion on the safety of HHCB through indirect exposure: http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_094.pdf
  26. ↑ REACH legislation: http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32006R1907&from=en
  27. ↑ "Oregon DEQ: Water Quality - Senate Bill 737 Implementation". www.deq.state.or.us. Retrieved 2016-04-26.
  28. ↑ EPA Workplan: https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/assessments-tsca-work-plan-chemicals
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