Safrole

Safrole[1]
Identifiers
CAS number 94-59-7 Y
ChemSpider 13848731 Y
KEGG C10490 Y
ChEMBL CHEMBL242273 Y
Jmol-3D images Image 1
Properties
Molecular formula C10H10O2
Molar mass 162.19 g/mol
Exact mass 162.06808 u
Density 1.096 g/cm3
Melting point

11 °C, 284 K, 52 °F

Boiling point

232–234 °C

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Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Safrole, also known as shikimol, is a phenylpropene. It is a colorless or slightly yellow oily liquid. It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil (although commercially available sassafras oil is usually devoid of safrole via a rule passed by the FDA in 1960, see here), or synthesized from other related methylenedioxy compounds. It is the principal component of brown camphor oil, and is found in small amounts in a wide variety of plants, where it functions as a natural pesticide. Ocotea cymbarum oil made from Ocotea pretiosa,[2] a plant growing in Brazil, and sassafras oil made from Sassafras albidum,[3] a tree growing in eastern North America, are the main natural sources for safrole. It has a characteristic "sweet-shop" aroma.

It is a precursor in the synthesis of the insecticide synergist piperonyl butoxide and the empathogenic/entactogenic drug MDMA.

Contents

Carcinogenicity

Safrole is regarded by the U.S. government to be a weak carcinogen in rats,[4] and considered by the European Commission on Health and consumer protection to be genotoxic and carcinogenic.[5] It naturally occurs in a variety of spices such as cinnamon, nutmeg, black pepper and herbs such as basil. In that role safrole is believed, although not proven, to make a small but measurable contribution to the overall incidence of human cancer, equal to the hazards presented by orange juice (due to limonene) and tomatoes (caffeic acid).[6] In the United States, it was once widely used as a food additive in root beer, sassafras tea, and other common goods, but was banned by the Food and Drug Administration (FDA) after its carcinogenicity in rats was discovered. Today, safrole is also banned for use in soap and perfumes by the International Fragrance Association.

According to a 1977 study of the metabolites of safrole in both rats and humans, two carcinogenic metabolites of safrole found in the urine of rats, 1'-hydroxysafrole and 3'-hydroxyisosafrole, were not found in human urine.[7]

Use in MDMA manufacture

Safrole is listed as a Table I precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. [8] Due to its role in the manufacture of MDMA, safrole and isosafrole as well as piperonal are Category I precursors under regulation No 273/2004 of the European Community.[9] In the United States, safrole is currently a List I chemical.

The root bark of American sassafras contains a few percent of steam volatile oil which is typically 75% safrole.[10] Attempts to refine safrole from sassafras bark are generally not economically viable due to low yield and high effort. Demand for safrole is causing rapid and illicit harvesting of the Cinnamomum parthenoxylon tree in Southeast Asia, in particular the Cardamom Mountains in Cambodia.[11] However, it is not clear what proportion of illicitly harvested safrole is going toward MDMA production, as over 90% of the global safrole supply (approx 2000 metric tons per year) is used to manufacture pesticides, fragrances, and other chemicals.[12][13] Sustainable harvesting of safrole is possible from leaves and sticks of certain plants.[12][13]

References

  1. ^ Merck Index, 11th Edition, 8287
  2. ^ Hickey M. J. (1948). "Investigation of the Chemical Constitution of Brazilian Sassafras Oil". Journal of Organic Chemistry 13 (3): 443–446. doi:10.1021/jo01161a020. 
  3. ^ Kamdem D. P., Gage, D. A. (1995). "Chemical Composition of Essential Oil from the Root Bark of Sassafras albidum". Journal of Organic Chemistry 61 (6): 574–575. doi:10.1055/s-2006-959379. PMID 8824955. 
  4. ^ T. Y. Liu; Chen, CC; Chen, CL; Chi, CW (1999). "Safrole-induced Oxidative Damage in the Liver of Sprague–Dawley Rats". Food and Chemical Toxicology 37 (7): 697–702. doi:10.1016/S0278-6915(99)00055-1. PMID 10496370. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6P-3X9415Y-3&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=8ec1ea8630ab130def74241535d2fc11. 
  5. ^ [http://ec.europa.eu/food/fs/sc/scf/out116_en.pdf Opinion of the Scientific Committee on Food on the safety of the presence of safrole (1-allyl-3,4- methylene dioxy benzene) in flavourings and other food ingredients with flavouring properties]
  6. ^ "Ranking Possible Cancer Hazards on the HERP Index". http://potency.lbl.gov/pdfs/herp.pdf. Retrieved 2007-03-19. 
  7. ^ Benedetti MS, Malnoë A, Broillet AL (1977). "Absorption, metabolism and excretion of safrole in the rat and man". Toxicology 7 (1): 69–83. doi:10.1016/0300-483X(77)90039-7. PMID 14422. http://www.ncbi.nlm.nih.gov/pubmed/14422. 
  8. ^ International Narcotics Control Board
  9. ^ Regulation (EC) No 273/2004 of the European Parliament
  10. ^ The Merck Index, 13th edition, Merck & Co, Inc, Whitehorse Station, NJ, copyright 2001.
  11. ^ Campbell, Sam (30 August 2009). "Harvested to make Ecstasy, Cambodia's trees are felled one by one.". GlobalPost. http://www.globalpost.com/dispatch/asia/090812/drugs-ecstasy-cambodia?page=0,0. Retrieved 2 September 2009. 
  12. ^ a b Harvesting Trees to Make Ecstasy Drug Tom Blickman (3 February 2009)
  13. ^ a b Piper hispidinervum: A Sustainable Source of Safrole Rocha S.F.R. and Lin Chau Ming. 1999. In: J. Janick (ed.), Perspectives on new crops and new uses. ASHS Press, Alexandria, Virginia.

External links