SCCP Opinion on Furanocoumarins in Cosmetic Products (SCCP/0942/05), ratified on the 13^th Dec 2005.

In a nutshell, many of you out there apparently believe that the imposition of a 1 ppm limit of furanocoumarins (FCF’s) in cosmetics, as proposed in this SCCP Opinion, would basically be the death knell for Natural Perfumery (and cause complete havoc in Conventional Perfumery). There is already an IFRA limit of 15 ppm for bergapten (5-MOP) in fragrances not washed off the skin exposed to sunshine – but it is Cropwatch’s opinion that this area is very little understood by perfumers, and the concentration limits are generally not observed by perfumery companies. This is partly due to a lack of information on FCF’s in ingredient specifications from oil trade suppliers – there’s a dearth of easily found information in the literature -  and little incentive to provide it; easy access of this information to customers would probably have a negative sales kickback (in terms of future potential usage of the ingredient) for the supplier involved.  

 

A fifteen-fold reduction of FCF’S from their present level, restricting them to 1 ppm in fragrances not washed off the skin and exposed to sunshine, would be potentially so serious for the art of perfumery since furanocoumarins occur widely across the Apiaceae & Rutaceae (see list below). Together with cuticular waxes, coumarins and polymethoxylated flavones, they make up a considerable part of the non-volatile residue of the peel oils of citrus oils like mandarin, sweet & bitter orange, grapefruit, bergamot & lime. Many of us had assumed – apparently mistakenly - that due to their relatively high molecular weights and very low vapour pressures, FCF’s would not be potentially steam distillable from vegetable material.  We have been told that this is incorrect: Daniel Joulain (Joulain 2006), for example, confirmed to Cropwatch that water/steam-distilled Malaysian rue oil (Ruta graveolens) contains over 10% of furanocoumarins (Jaacob 1989) and that he had personally supervised Jaacob’s analysis. Perhaps I now need to go into a huddle with several of my colleagues, whilst we ask ourselves some serious questions about our comprehension of the theory of steam distillation & Daltons Law of Partial Pressures!

 

Whilst analysts from the big Corporates have been fairly quick to rush out a method for the quantification of furanocoumarins in citrus oils (e.g. Frerot & Decorzant, Nov. 2004) and it is obvious from their published remarks that the authors knew this move was coming (restriction of FCF’s to 1 ppm) before many of us less well-connected aroma industry drones had appreciated it. Further, the cost of the analytical equipment needed to determine the FCF contents (HPLC coupled with UV, fluorescence & mass detection) is beyond the resources of many of us affiliated to the smaller aroma concerns. The financial exclusivity in the ability to estimate FCF’s to the cash-rich larger aroma concerns, is not healthy, and not in the overall best interests of the industry.

 

Cropwatch has attempted to quickly put together some data on natural ingredients that contain FCF’s. If readers have further information, we would be grateful if you shared it with our supporters and ourselves. Remember that under ordinary circumstances, citrus oils such as FCF-free bergamot oil are often adulterated, but that when asked, oil trade companies & organisations are hardly going to give (or be given) typical (adulterated/blended) citrus oils to submit to bodies such as RIFM to work with. This gives an artificiality to the situation, and is one of the failings of the system as it stands, which is so trade-reliant for samples and information.

 

Finally a non-scientific small sampling of UK perfumer’s views on this matter indicates that due to their position as key ingredients, if bergamot, petitgrain and coriander qualities are found to have FCF contents which subsequently interfere with their use in perfumery to a greater extent than at present, the concensus was we might as well all give up and go and work at Tesco’s.

 

Paucity of - /Conflicting Data on Phototoxic Potential of Natural Botanical Ingredients.

 

Ammi visnaga oil Ammi visnaga (L.) Lam.

CAS n°  - - -

Cropwatch comments: Commercially produced oil, used in aromatherapy.

For: Contained photochromones khellin & visnagin used to pigment skin via UV in vitiligo treatment; photochemical cross-linkage to DNA disputed by photo-sensitised DNA cleavage noted. (Chen & Kagan 1993).

 

Angelica root oil/extracts – all origins (solvent extracts often incorrectly sold as an ‘oil,’ esp. with Chinese oils). 

Angelica archangelica L. ssp. archangelica var. sativa (Miller): European oil.

A. sinensis (Oliv.) Diels. Chinese oil.

A. koreana Maxim. Contains isoimperatorium, oxypeucedanin.  

CAS n° EU 84775-71-7 (A. archangelica spp. & subspp. only).

For: Zobel & Brown (1991) show psoralen, xanthotoxin and bergapten in fruits & seeds of A. archangelica. RIFM found Angelica root oil phototoxic. Opdyke D.L.J. (1975). IFRA (2001) recommends 0.8% max. of Angelica root oil in products applied to skin then exposed to sunshine.

Against: Essential oil obtained by steam distillation of roots of A. archangelica claimed free of furanocoumarins by EMEA (1996); root & seed essential oil also claimed to be free of FCF’s therefore not phototoxic by Leung (1996).  RIFM found angelica seed oil non-photo-toxic: Opdyke (1974) through Tisserand & Balacs (1996) page 116.

 

Aniseed oil Pimpinella anisum L.

CAS n° EU: 84650-59-9

For: Plant tissues contain bergapten (Leung 1996).

Against: Steam distilled seed oil not traditionally considered phototoxic.

 

Bergamot oil cold pressed – all origins Citrus aurantium L. subsp. bergamia (Risso et Poit.) Engl.

Cropwatch comments: Bear in mind that the cultivation of the Bergamot tree (Calabria, Ivory Coast) is deceasing – perhaps partly due to the efforts of career toxicologists in reducing demand?

CAS n° EU: 89957-91-5.

For: String of earlier studies (see BoDD website) show that bergamot oil- containing perfumes are phototoxic. [Cropwatch comments:  it must be remembered that bergamot oil concentrations in fragrances were likely to be higher during this older period; voluntary restrictions on concentrations deployed since then & use of FCF type may have reduced adverse reaction frequency]. Photoxicity of bergamot oil demonstrated on mouse skin when irradiated with UV light (Opdyke 1973). IFRA restricts to 0.4% in fragrances not washed off skin, exposed to sunshine.

Against:

“Reported acute phototoxic side effects from perfumes are rare, repeated exposure to sunlight after perfume application uncommon… no reports of increase in epithelial tumour formation on areas of skin habitually exposed to perfume (Dubertret et al. 1990 & Chouroulinkov et al. through Lawrence 1991).

Bergamot oil only “known as a mildly phototoxic ingredient” (Nathalie et al. 2006).

Bergamot oil samples “can vary in phototoxic capacity” – Zanoun et al. (1974) - through BoDD.

“Despite its increasing application, there are only a few recent reports of phototoxic reactions to bergamot aromatherapy oil.” - Kaddu et al. (2001).

“Cropwatch estimates that hundreds of thousands of body massages world-wide have been given by aromatherapists using (diluted) bergamot oil, but we only know of a vanishing small number of adverse reactions. We need to understand why this is exactly.”

 

Bergamot oil Distilled.

For: Rectified oils may contain ~ 300 ppm bergaptene according to one Italian manufacturer.

Against: Up to now has been generally assumed to be non-phototoxic e.g. by S. Arctander (through Opdyke 1973).

 

Bergamot Oil FCF.

For: Contains from zero to 9-10 ppm bergaptene (Cropwatch consensus of several manufacturers).

Cropwatch comments: higher boiling fractions of distilled bergamot oil (which contain valuable odour compounds) may be treated by column chromatography, chemo-absorbtion techniques or by solvent extraction to reduce overall FCF content, and are added back to low boiling fractions (thanks to D. Joulain & staff from Italian citrus producers who don’t want to be named, for this information).

 

Carrot Seed oil Daucus carota L. subsp. carota

CAS n° EU: 84929-61-3

For: Slight photosensitising effect known from whole carrots (Ceska 1986).

Against: Not previously considered photo-toxic. Not found photo-toxic by modified 3T3 neutral red uptake assay (Nathalie et al. 2006).

 

Cedrat oil: peel oil Citrus medica L.

CAS n°:  68991-25-3.

Against: Peel oil claimed to contain negligible amount of FCF’s by certain Italian citrus oil manufacturers.

 

Celery Seed oleoresin/oil. Apium graveolens L. var. dulce (Miller) DC.

CAS n°  EU: 89997-35-3

For: FCF’s known in stems, especially if diseased.

Against: Oleoresin & solvent extracts at least, expected to contain FCF’s.

 

Clementine Terpenes (Italy) Citrus reticulata Blanco var. clementine.

CAS n°  EU: 68608-34-4

No data.

 

Coriander Leaf oil Coriandrum sativa L.

CAS n° EU : 84775-50-8

No data

 

Coriander oleoresin/oil Coriandrum sativa L.

CAS n° EU : 84775-50-8

For: Fruits contain psoralen, angelicin etc. (Leung 1996).

 

Dittany oil (syn. Gas Plant) Dictamnus albus L.

CAS n° : - - -

For: FCF’s known to occur in plant.

 

Grapefruit oil expressed – all origins Citrus paradisi Macf.

CAS n° EU: 90045-43-5.

Contains up to 1.4% coumarins & furanocoumarins.

For: Restricted IFRA to 4% in fragrances not washed off skin exposed to sunshine.

Against: Expressed oil not phototoxic: Sams (1941), Opdyke (1974).

 

Kaffir lime oil pressed/leaf oil Citrus hystrix DC.

CAS n° - - -

Against: Claimed to contain negligible amount of FCF’s by some citrus oil manufacturers.

 

Lemon oils cold pressed  - all origins Citrus limon (L.) Burm.

CAS n° EU: 84929-31-7.

For: Photo-toxicity of lemon oil cold-pressed almost totally due to oxypeudedanin & begapten; contents and ratios of these compounds varies according to origin; average bergapten ~87ppm & oxypeucedanin 26-728ppm (Naganuma et al. 1985). Opdyke (1974a) previously described lemon oil phototoxicity and IFRA currently recommends limit of 2% in fragrances not washed off skin exposed to sunshine.

 

Lemon oil Distilled.

No data

 

Lemon Oil Terpeneless

No data

 

Lemongrass Oil West Indian Cymbopogon citratus (DC) Staph.

CAS n° EU: 89998-14-1.

For: Slightly photo-toxic for C. citratus (as shown by modified neutral red uptake assay: Nathalie et al. 2006).

Against: We have: E.I. & W.I. lemongrass oils found non-photo-toxic Opdyke D.L.J. (1976) FCT 14, 455 & 457.

Other statements: W.I. Lemongrass oil phototoxicity ‘has not been determined’ Opdyke (1976) through Leung (1996). E.I. Lemongrass phototoxicity ‘is not known’ Opdyke (1976), again through Leung (1996).

Cropwatch comments: We’re confused!

 

Lime oils cold pressed – W.I.: Key or Mexican lime Citrus  x aurantiifolia (Christ.) Swingle, & Persian or Tahitian lime C. latifolia Tanaka. 

CAS n° EU: 90063-52-8.

For: FCF content noted by Pathak (1962). IFRA (1992) limits to 0.7% in fragrances not washed off skin exposed to sunshine based on Opdyke (1974b) its bergapten content as reported in J.A.O.A.C. (1969) 52(4),727.

 

Lime oil distilled.

Against: Distilled lime oil is not photo-toxic (Tisserand & Balacs (1996) p147, quoting Opdyke 1974).

 

Lime oil terpeneless.

No data

 

Limette peel oil Citrus limetta Risso

CAS n° - - -

 

Mandarin oils - cold pressed Citrus reticulata Blanco.

CAS n° 84929-38-4.

For: IFRA advises typical 5-MOP content of cold-pressed mandarin oil is 250 ppm.

 

Mandarin oil folded Citrus reticulata Blanco.

No data found

 

Neroli oil C. x  aurantium L. flowers.

CAS n° EU: 72968-50-4.

For: Phototoxic reactions to oil reported historically (Greenberg & Leicester 1954 - through BoDD).

 

Orange Peel oil, Bitter Citrus aurantium L. subsp. amara L.

CAS n° 68916-04-1

For: Based on RIFM work, IFRA limit of 1.25% based on uncertainty factor imposed over data of Kaidbey & Kligman (1980).  

 

Orange Peel oil Sweet Citrus sinensis (L.) Osbeck

CAS n° USA: 8008-57-9

For: ‘Probably phototoxic’ (as shown by modified Sudan Red uptake assay) Nathalie et al. (2006). Peels contains bergapten.

Against: Not phototoxic, not restricted IFRA.

 

Orange oil sweet folded Citrus sinensis (L.) Osbeck

No data found

 

Orange oil sweet terpeneless Citrus sinensis (L.) Osbeck

No data found

 

Parsley herb/seed oils/oleoresin Petroselinium crispum (Miller) A.W. Hill.

CAS n° EU: 84012-33-9

For: Toxicity associated with furanocoumarin content Newall et al. (1996).

IFRA advises that typical 5-MOP content of parsley leaf oil is 20 ppm.

 

Parsnip extracts/oil Pastinaca sativa L.

CAS n° EU: 90082-39-6

For: Tissues contains bergaptene, xanthotoxin, angelicin, sphondin, isopimpinellin, imperatorin.

 

Petitgrain Bigarade oil C. aurantium / C. aurantium v. aurantium  leaves.

CAS n° EU: 72968-50-4.

For: Phototoxic reactions to oil reported (Greenberg & Leicester 1954, Klarmann 1958 – through BoDD).

Against: Petitgrain oil not phototoxic: RIFM monograph FCT 20, 801 Sp Issue VI.

Cropwatch comments: in real life, other Petitgrain oils: mandarinier, citronnier, bergamottier, are often of variable composition (blends of several oils).

IFRA advises that typical 5-MOP content of Petitgrain mandarin oil is 50 ppm.

 

Rue oil Ruta graveolens L.

CAS n° EU: 84929-47-5

For: Jaacob (1989) through Joulain (2006): steam distilled Malaysian rue oil contains psoralen (1.3%) and bergapten (7.2%).

IFRA limits rue oil to 0.15% in fragrances not washed off the skin exposed to sunshine.

Cropwatch comments: rue oil is not much used in perfumery.

 

Satsuma oil (Japan, USA) Citrus unshiu Marc.

No data

 

Skimmia laureola oil India, Kasmir Skimmia laureola Sieb. et. Zucc. ex Walp.

Cropwatch comments: steam distilling leaves yield oil produced on commercial scale, which has been compared as similar in odour to petitgrain.

CAS n°: - - -

For: 25 Psorelens & coumarins amongst identified FCF’s (Pathak & Pant 1977; Radzan et al. 1986). Acetone extract of dried leaves yields bergatene, xanthotoxin etc. (Bhargava et al. 1973).

 

Star Anise Oil Illicium verum Hook f.

CAS n° 84650-59-9.

Against: Not previously found phototoxic to mice & swine (Opdyke 1975).

 

Sweetie oil Citrus paradisi x Citrus grandis. 

CAS n° - - -

No data.

 

Tangerine oil – cold pressed Citrus reticulata Blanco var. mandarin

CAS n° EU: 93686-22-7.

For: IFRA advises typical 5-MOP content of CP oil is 50 ppm.

Against: No FCF monomer/dimer found in 12 tangelos & 2 monohybrid tangerine varieties frown in Florida (Widmer 2005).

 

Yuzu oil – cold pressed Citrus junos Sieb. ex Tanaka)

CAS n° USAS: 233683-84-6.

No data.

 

It is reasonably obvious that the SCCP need to look further into this veritable Pandora’s box that they have just opened – getting the lid back on may prove pretty difficult. Basically it is evident that the SCCP haven’t realized the scope of the implications of their ‘Opinion’, or are happy to relegate perfumery to an increasingly synthetic future.

 

Several of you are suggesting that the combination of the EU’s obsession with the precautionary principle, continual negative advice from the advising ‘career toxicologists & dermatologists’, the complete inability of ‘expert’ committees to evaluate the benefit side of the risk-benefit equation, together with he complicity of essential oil trade organisations in supplying requisite data to EU legislators, has now reached the point of extinction for the continued well-being of industry at the user-end of aromatic products. Some are suggesting the establishment of ‘an alternative’ voluntary regulatory authority, with a better appreciation of the predictable consequences of proposed ingredient regulation, as this ability is evidently missing in the present system.

 

Whilst we haven’t examined the implications of the SCCP/0942/05 Opinion, in any great detail for what is left of the perfumery industry, Cropwatch is open, in principle, to debate & suggestions on a better way to regulate natural product usage in Cosmetics, Perfumery, Natural Perfumery, Biocides, Aromatherapy, Herbalism etc. In our opinion, it is apparent that the present regulatory system has failed - it does not command universal respect, the ‘expert’ committees produce work that is both incomplete & often seriously flawed, and those that oversee the Opinions are insufficiently expert across the broad range of skills required to do the job properly. Further, those bodies many of us formerly regarded as reasonably independent (like IFRA), are now seen as part the EU “big brother” diktat mentality. The culture of corruption in the EU and the way that whistleblowers are dealt with is hardly a new subject (see for example Eurosoc Two 2004). We think that the deliberate attempts to sideline & ignore Cropwatch and not to take its ‘awkard’ opinions on board over the past year by the machinations of the EU regulatory machine are now sufficiently advanced that Cropwatch can prepare its case for presentation to the Ombudsman.

 

This aside, could another body do the job better? - we think that it could, but this would depend on a critical mass of support being established. The rate at which this support is being pledged to Cropwatch is encouraging, but we do need you professors, doctors, technicians, students and most of all, you ordinary folk, interested in the natural aromatic products area, to contribute & continue help us grow. 

 

References:

Bhargava K.K. & Seshadri T.R. (1973) Current Sci 42, 59-60.

 

Ceska O. et al. (1986) “Furanocoumarins in the cultivated carrot, Daucus carota. ” Phytochem. 25, 81-3.

 

Chen X. & Kagan J. “Photo-sensitised cleavage & cross-linking of pBR322 DNA with khellin & visnagin” J. Photochem. & Photobiol. B: Biology  20(2-3), 183-189.

 

Chouroulinkov I., Lasne C. & Nguyen-Ba (1989) “Study with 5-MOP, bergamot & Bergasol in mouse skin carcinogenicity tests. In Psoralens: Past, Present & Future of Photochemoprotection & other biological activities.” Eds: T.B. Fitzpatrick, F. Forlot, M.A. Pathak & F. Urbach pp345-355. John Libby Eurotext. Paris.

 

Dubertret L., Serraf-Tircazes D., Jeanmougin M., Morliere P., Averbeck D. & Young A.R. (1990) “Phototoxic properties of perfumes containing bergamot oil on human skin. Photoprotective effect of UVA and UVA substances.” J. Photochem. Photobiol. B: Biology. 7, 251-259.

 

EMEA (1996): Committee for Vertinary Products May 1988 (ref EMEA/MRL/412/98-FINAL. Root & seed essential oil also claimed to be free of FCF’s by Leung (1996). 

 

Eurosoc Two (2004) “Watching Big Brother” – see www.eurosoc.com/news/

 

Frerot E. & Decorzant E. (Nov 2004) “Quantification of total furanocoumarins in citrus oils by HPLC coupled with UV, flouresence, & mass detection.” J. Agric. Food Chem. 52(23) 6879-86.

 

Greenberg L.A. & Lester D. (1954) Handbook of Cosmetic Materials. Interscience NY.

 

Jaacob K.B. et al.  (1989)  J. Essent. Oil Res. 1, 203.

 

Joulain D. (2006): Private communication to author.

 

Kaddu S., Kerl H., & Wolf P. (2001) “Accidental bullous phototoxic reactions to bergamot aromatherapy oil.” J. Am. Acad Dermatol 45(3), 458-461.

 

Kaidbey, K.H. & Kligman, A.M. (1980). “Identification of contact photosensitizers by human assay.” Current Concepts in Cutaneous Toxicity, 55-68. Academic Press, NY. Report No 1995.

 

Klarmann E.G. (1958) “Perfume Dermatitis” Ann. Allergy 16, 425.

 

Lawrence B. “Progress in Essential Oils” Perf. & Flav. Vol 10 Sept/Oct 1991 p78.

 

Leung A.Y. & Foster S. Encyclopaedia of Common Natural Ingredients used in Food, Drugs & Cosmetics 2^nd edn. Wiley-Interscience pub. 1996.

 

Nathalie D., Yannik G., Caroline B., Sandrine D., Claude F., Corrine C., Pierre-Jacques F. “Assessment of the Phototoxic Hazard of Some Essential Oils using Modified 3T3 Neutral Red Uptake Assay.” Toxicol in Vitro 20(4), 480-489.

 

Opdyke D.L.J (1973) Food Cosm.Toxicol 11, 1035.

 

Opdyke D.L.J. (1974) Food Cosm.Toxicol 12, 723.

 

Opdyke D.L.J. (1974a) Food Cosm.Toxicol 12, 725

 

Opdyke D.L.J. (1974b) Food Cosm. Toxicol. 12, 731

 

Opdyke D.L.J. (1975) “Angelica Root Oil” FCT 13, (Suppl), 713.

 

Pathak H.D & Pant J.N. “Chemical examination of Skimmia laureola Sieb. & Zucc. Indian Perf. 16(1), 454-50.

 

Pathak, M.A., Daniels, F. and Fitzpatrick, T.B. (1962) “Presently known distribution of furocoumarins (psoralens) in plants”. J. Invest. Derm. 39, 225.

 

Radzan T.K., Qadri B., Harkar S. & Waigt E.S. (1986) “Chromones & Comarins from Skimmia laureola.” Phytochem. 26(7), 2063-2069.

 

SCCP Opinion on Furanocoumarins in Cosmetic Products (SCCP/0942/05) – available at  www.europa.eu.int%00/comm/health/ ph_risk/committees/04_sccp/docs/sccp_q_042.pdf

 

Tisserrand R. & Balacs T. (1996) Essential Oil Safety for Health Professionals

Churchill Livingstone.

 

Widner M. 2005 “Tangerine/grapefruit Hybrids (Tangelos) do not have Furanocoumarins Associated with Grapefruit/Drug interactions” J Food Sci. 70(4), 307-312.

 

Yaacob K.B. (1989) et al. J. Essent. Oil Res. 1, 203.

 

Zanoun S., Hall I., Johnson B.E. & Frain-Bell W. (1974) “A study of bergamot sensitivity” Brit J. Derm. 91(Suppl 10), 14.

 

Zobell A.M. & Brown S.A. (1991) “Furanocoumarin concentrations in fruits and seeds of Angelica archangelica” Environmental and Experimental Botany 31(4), 447-452