the aromaconnection blog

Struggles of Honest Aromatic Crops Businessmen in Afghanistan

Yesterday's 'Morning Edition' on NPR featured an heroic effort in the hills of Afghanistan by Shafiq Azizi and his business partners to grow and extract roses and other aromatics as an alternative for the poppy growers who trade in the world-wide heroin industry.  Hoping to set an example, they have expended frustrated efforts and a considerable sum of invested money.  Sounds idyllic, however, Shafiq  and Barnett Rubin (an Afghanistan expert and owner of the company that supports Azizi's efforts) are finding the prospect of legal business in Afghanistan is not so attractive to those already engaged in growing poppies.  Also, the corrupt Afghanistan government is hindering any progress or growth of the rose production for perfumery by soliciting bribes and unduly hindering their operations.  An initial $29,000 investment funded the first rose fields and the building of a commercial still, but major setbacks have the investors backing out.  Hopefully, local entrepreneur Abdullah Arsallah's determination to break the cycle of the drug business, and the willingness of a farmer in a nearby village, Haji Ibrahim, will revive the effort. You can read this complete report by Ivan Watson and view video.  We will attempt to keep an eye on this situation and report further progress.       

Perfume Politics: The Oppressive Perfumer's Guild

Guilds are perhaps the precursors of modern trade unions, and also, paradoxically, of some aspects of the modern corporation.  Guilds are actually small business associations and have little in common with trade unions.  They are more like cartels in that they assume exclusive privilege to produce certain goods or services or dictate standards of a profession.  Guilds can establish restrictive guidelines or a rigid system and can exclude those who do not abide.  Guilds emerged with a similar spirit and character to the original patent systems and are not generally conducive to a democratic free flow of development and interaction.   

In the modern democracy, we have created nonprofit organizations or NGO's intended to benefit a group by collective efforts and by providing public education or  services that benefit society.  Legal nonprofit corporations receive tax relief, but are required to provide public reporting and transparency.  Such nonprofit endeavors are usually governed democratically and operated by officials periodically elected from within the membership.  This creates a structure that will evolve the endeavor into the future separate from and not dependent on or owned by any one member. 

The French Perfumer's Guild of antiquity was perhaps the worst example of the power a Guild over its members.  Established by an edict of King Philippe-Auguste in 1190 (reconfirmed by patent letters by King Jean in 1357, again by King Henri III in 1582, and again by Louis XIV in 1658, the "confrerie des Maitres Gantiers et Parfumeurs") that primarily gave glovemakers of the extended medieval period the exclusive right (i.e., monopoly) to manufacture and sell cosmetics of all types.  Why glovemakers, you ask?  Gloves were made from leather tanned using urine and other toxic and putrid substances and needed to be scented before they could be respectably worn.  The glovemakers were wealthy manufacturing businesses and they were quite adept at organized efforts to lobby each respective monarchy, reminding of the importance of their role in medieval society and thereby acquiring the sanction necessary to maintain their monopoly.  And, one can also suspect that favors were extended.  Today, we might call them bribes.  As you can see, this monopoly continued for a long time and was grounded in the necessity for perfuming what would otherwise be unusable products - leather gloves.   The corporation or guild, headed up primarily by master glovemakers,  established the sole credentials of those who could sell gloves as well as perfumed goods and dictated the kinds of products they could manufacture . . . a long list including sachets with perfumed powders, compositions used in burners for environmental scent, pomades for the hair, soap, cosmetic creams, scented gloves and even tobacco.  A quaint novelty to us today, but in common use then, was the "oyselets de Chypre."  These were cloth birds in bright colors, decorated with feathers and stuffed with aromatic powders, then placed in ornate cages and hung from ceilings or walls to add fragrance to a room.

By 1750, there were 250 master perfumers, members of the corporation who had served 4 years as an apprentice and an additional 3 years as "compagnons" before reaching the status of master.  For all intents and purposes, they were slaves, not free (until the Revolution that is) to work outside the confines of the guild or to develop their own trade and commerce.  Only rarely were there exceptions, a notable one being René Le Florentin, Catherine de Medicis's personal and favorite perfumer.  Le Florentin had a reputation for talent in creating scents and fabricating poisons!  And, obviously Catherine was well positioned to demand for him premature status.

Everything changes.  Along  came the French Revolution, rendering perfume and other objects considered frivolous luxury symbols of excesses of the aristocracy out of favor.  With the exception of popular scents like, "parfum á la Guillotine".  Under the Terror, choice of scent indicated political affiliation, a kind of odorous password.  Politically correct scents could literally save one from execution.  Napoleon's return from conquering (so he claimed) Egypt, along with his renowned heroic status gave him the power to re-establish the importance of French manufacturing to the glory of the nation.  His fondness for cologne bode well for the lagging perfume industry, establishing imperial commissions as well as scientific and technological research in organic chemistry . . . a science that would revolutionize the perfume industry in the latter half of the 1700's.   Thus, the adjective "French" is aligned with the noun "civilization" and under a new empire, cosmetic luxury products had a more general and populist allure.

One would hope that we are beyond the oppressive restrictions imposed on the medieval creative perfume artists of the day and that individuality and inventiveness are the modern dictates for his or her endeavors and acceptance.  And, that perfume guilds are fashioned after the democratic principles of modern non-profits and NGO's. 

References

Stamelman, Richard, "Perfume: A Cultural History of Fragrance from 1750 to the Present", 2006, Rizzoli International Publications, Inc.

Classen, Constance, Howes, David, Synnott, Anthony, "Aroma: The Cultural History of Smell", 1994, Routledge Press

Newman, Cathy, "Perfume: The Art and Science of Scent",  1998 National Geographic Press

http://www.wikipedia.org/

Cropwatch at the Cross-Roads

Cropwatch Statement

After 4 or 5 years of continuous activity, Cropwatch has some choices to make. Do we go on the way that we have been, snapping at the ankles of those who run & regulate the aroma industry so badly, or should we 'old dogs' learn some new tricks? Cropwatch supporters, and organisations sympathetic to our aims, regularly offer us donations and advise us of potential sources of grants, to which we have always said 'no thanks, we're non-financed'. Our current thinking is that this might be a mistake, since we are limiting our potential effectiveness. .

We are certainly not asking everyone for money, but we are asking you to help us with some feedback on how a financial input could potentially help the aroma world to become a better & fairer place, so please mail us if you have any thoughts or ideas.

Our initial list of ideas to use donated funding would be:

1. To finance risk/benefit studies on natural aromatic products. This research is needed because the existing major players such as IFRA/RIFM, are set up only to investigate the risks/hazards of fragrance ingredients (but not the benefits), & EFFA can only present the safety risks of essential oils, absolutes, resinoids etc in terms of the imagined hazards of the individual contained chemicals, rather than adopting a holistic approach for the aromatic ingredient as a whole. Therefore both organisations are badly positioned to defend natural aromatic ingredients against the current avalanche of restrictive legislation. The EU Commissioners have previously declined to accept safety-data based on risk/benefit considerations, although we believe this policy to be untenable in the long-term - it is the norm in virtually every other regulatory area (biocides, agricultural chemicals, pharmaceuticals etc).

[Neither is this just a European problem. The U.S. House Committee on Energy and Commerce have just announced draft legislation (Global Harmonisation Act 2008) intended to stimulate discussion on how to provide adequate funding and authority for the FDA to ensure the safety of the nation's food, drug, medical device and cosmetic supply in an increasingly globalised marketplace. The draft legislation already highlights several areas which will affect the fragrance industry]. 

2. To develop statistical data on the adverse effects of restricted & prohibited aromatic materials. This data would be a potential bombshell to blow apart the over-precautionary approaches of the cosmetic regulators and career toxicologists, who are in such a powerful position in global regulatory circles. Where this data exists (e.g. the Schnuch data on alleged allergens) it is already causing red faces. The EU Commissioner has previously indicated to Cropwatch (Brussels 2007) that this type of adverse reaction data is inadmissible as safety evidence. But if you are familiar with English history, you might recall that King Canute failed to hold back the waves and so his followers realised he was not all-powerful. So too, the regulators will not be able to ignore the fact that many restrictions on natural products are based on corporate toxicological constructs which don't manifest in the great numbers of negative health effects predicted.

3. To assist with the growing & production of useful commodities from threatened aromatic plants, for cosmetic, aromatherapeutic, flavour & medicinal outlets, in a way that benefits the poor.

4. To set up or help set up a natural aromatics products professional body, with the help of other interested parties. Already we can identify several sub-divided areas which badly need assistance: natural perfumery, the use of naturals within conventional perfumery, natural biocides, herbal drugs & medicines, aromatherapy, natural cosmetics etc. 

5. The lobbying of officials & regulators. As we have seen, the more the establishment closes ranks (and its mind) to contrary & dissenting views, the more popular support we have been able to attract. In terms of numbers we are potentially a powerful force. However we have to ask ourselves whether there is any point in continuing the lobbying game. Many of the points we make go unanswered because the officials involved are not sufficiently technically adept or experienced to even understand the arguments put forward. So is it better to plough ahead with a voluntary regulatory system of our own making - at least we might have the experience, familiarity & resources to do a better job. The enormity of the task is detracting, but this is put more into perspective if sufficient funding were to be available.  

6. To keep the flame of our traditional perfumery heritage alight. When we read that several major aroma corporations are training fledgling perfumers in pure synthetic perfumery, it makes us wonder if the world has gone quite mad. Once perfumers used to be creative artists with forthright temperaments, views and opinions, passionate about their art. Now, are we all to be reduced to company drones? I was related a story recently concerning a certain essential oils salesman who offered unmarked samples of  real good quality Bulgarian lavender oil, and a synthetic lavender construct to a group of young perfumers at a certain megacorporation. The group preferred the artificial lavender construct because "it smelled like linalyl acetate, like its supposed to."  Heaven help us! But maybe some of us 'old-timers' should organise courses & lectures to pass on the 'ancient knowledge of the art of perfumery' before it is lost forever.   

OK, after 5 or so years of trying, we pretty much know what the problems facing us are - what we don't have is a consensus on the best way to solve them. Maybe you can help?

Cropwatch Team

Technorati Tags: Cropwatch,natural aromatic products,perfumery,natural perfumery

Furanocoumarins in Cosmetics: What’s all the Fuss About?

Copyright © Tony Burfield April 2008 

Preamble 

The EU Cosmetics Commission, well known for setting the pace worldwide for
(over-)-precautionary cosmetics legislation, is seemingly determined to limit furanocoumarins (FC’s) in retailed fragranced products to minutely low levels. This is because they consider that these materials present a potential photomutagenic & photocarcinogenic risk to users, when products containing these items are applied to the skin and subsequently exposed to sunlight. The IFRA proposals to limit FC’s in such products are being opposed by Cropwatch amongst others. Cropwatch favour no furanocoumarin restrictions for aroma ingredients, but propose reliance on an alternative warning label solution (‘only wear under heavy clothing’ or ‘if applied to the skin, do not expose to sunlight for 12-24h’). Major sources of FC’s in fragrances are citrus oils, especially cold-pressed citrus oils, and FC’s are especially prevalent in lemon, grapefruit, lime & bergamot qualities. We are also exposed to furanocoumarins from vegetables & fruit in the diet, which may also slightly increase our chances of developing adverse outcomes such as melanoma after sunlight exposure, or which may interfere with the metabolism of prescribed drugs (e.g. from consumption of grapefruit juice etc.). However, as we have learned, because of the way that the EU legislature is set-up & advised, more stringent precautionary legislation applies to cosmetics within the EU than it ever does for foodstuffs. 

Cropwatch FC Data-Base 

Because of the lack of accurate information on FC’s in aromatic raw material ingredients, Cropwatch has extensively updated its Furanocoumarins A-Z listing in Natural Aromatics (the latest update can be seen at http://www.cropwatch.org/FC A-Z.pdf). Cropwatch took on the task of constructing this data-base because of the relative unavailability of accurate information on citrus oil furanocoumarin distribution to essential oil users and to perfume formulators. As can be checked from the data-base, the information on furanocoumarins which IFRA/RIFM has previously published,  is often insufficiently detailed (in terms of botanical species, variety, geographical region, processing methodology and time of season) to be particularly useful. Cropwatch has also included its previous notes on the importance of citrus ingredients to the perfumery art, and also presents notes & references on photo-toxicological topics, as well as notes on individual FC’s and their occurrence in natural products.

The information on furanocoumarin concentrations within citrus & other aroma ingredients is needed in the light of IFRA's proposals, currently set before the EU Commission, whereby six major marker furanocoumarins have been identified by IFRA, and it is proposed that their concentration (in any combination) within retailed fragranced cosmetics should not exceed 5ppm for products left on the skin, and 50ppm in wash-off products. Although IFRA's proposals are slightly less severe than the previous blanket proposal by the SCCP to limit all furanocoumarins (whether phototoxic or not) & furanocoumarin-like substances (nobody knows what this definition means!) to 1ppm in cosmetic products across the board, they are still unworkable. In particular the FC proposals spell the end of the line for natural perfumery, as exemplified in traditional citrus colognes, chypres, fougeres etc. Eighty to ninety percent of male fragrances (and a smaller percentage of female fragrances) also contain citrus oils, and so will be severely affected also. But, since DG-Ent/SCCP has a history of rubber-stamping IFRA policy, it can only be assumed that EU legislation will eventually reflect IFRA’s proposals. However, Cropwatch has learned that many cosmetic companies are sufficiently brave and independent-thoughted enough to plan to simply ignore any rulings on future furanocoumarin limitation. 

As can be verified from the data-base, the degree of risk associated with the phototoxicity/photocarcinogenicity of furanocoumarin-containing essential oils, such as cold-pressed bergamot oil, has never been universally agreed amongst toxicologists & dermatologists, over the past several decades. Slightly modifying a passage from the data-base might be illuminating here. In 1988, Young et al. found that a bergapten induced tan is protective against the DNA-damaging effects of solar radiation (bergapten is a major FC in bitter orange, grapefruit, bergamot & other citrus peel oils). Following the finding that the use of bergapten applied in sunscreen enhanced the body’s natural protection for several weeks, even when the sunscreen plus bergapten use was discontinued, funds were provided by the Cancer Research Campaign & Laboratoires Bergaderm to develop a lotion to improve the body’s natural defences (Anon 1992). This product, believed to contain some 30ppm bergapten, was eventually trialed as reported in the media (Hunt 1992). However worries about the furanocoumarin photocarcinogenicity led the EC to order Laboratoires Bergaderm not to release their bergapten-containing Bergasol product onto the market past July 1996 (Goldemberg 1996), eventually forcing Laboratoires Bergaderm into liquidation. It is very difficult for Cropwatch to predict whether, on balance, this EC action subsequently caused deaths or saved lives. What it does illustrate is the rising power of non-technical, non-elected bureaucrats, who are even prepared to act in areas where there is not a 100% consensus of scientific opinion, against the policies of bodies like the Cancer Research Campaign (for references see the A-Z listing). [Thanks to Martin Watt for supplying articles verifying this story]. 

To recap the inadequate state of knowledge that we have on FC’s, the full range of identities of FC’s within many individual citrus & other essential oils (e.g. angelica & cumin) is still incomplete. The properties & phototoxic effects of individual furanocoumarins too are largely unknown, as very pure samples of the materials have been difficult or impossible for toxicologists to obtain. The mutual interactions of substituted coumarins & furanocoumarins within essential oils, their actions when applied to biological systems (the skin) remain virtually unexplored. Risk/benefit considerations of complex biological substances containing furanocoumarins are hardly touched on, and are unlikely to be since RIFM is only geared to evaluate risk, and the Cosmetics Commission still lives in the Dark Ages as it will not accept risk/benefit evaluations (although it will have to eventually). Further, three recent papers on the (pseudo)photo-plastogenicity of cosmetic ingredients (titanium dioxide, zinc oxide) highlight the fact that the methodology of these in vitro studies are seriously flawed – so much so that one group of researchers (Lynch et al. 2008 – see the data-base!) has called for an urgent review of phototoxicity testing techniques as applied to cosmetic materials. Yet, despite these fundamental detractions, some unseen hand appears to be cracking the whip over the EU Commissioners heads, who in turn appear to be exerting pressure on industry for answers & progress. But the science simply isn't there to justify any hasty and ill-conceived legislation on these matters. We don't even know how therapies involving furanocoumarins, such as PUVA, actually work. 

End Thoughts 

In summary, proposals to severely limit furanocoumarins in cosmetic products to such proposed minute levels mentioned above will prohibit the effective use of many citrus oil ingredients within fragrances. Many of us will see this eventuality as an act of cultural vandalism, and we known that many MEP's at Brussels, too, are concerned at the way the Cosmetics Commissioners are systematically wrecking our cultural heritage of high-art perfumery. Enough is enough. It is not the brief of the EU Cosmetics Commission to permanently damage the art of perfumery by denying perfumers the use of 'un-messed about' citrus ingredients, 

Cropwatch wishes to thank those who have contributed, and are continuing to contribute, information to the furanocoumarins data-base. Updates to the data-base will continue to be issued.

Tony Burfield for Cropwatch

Technorati Tags: furanocoumarins,fragrance,furanocoumarin,Cropwatch,citrus oils,EU Cosmetics Commission,IFRA

Comment: The QRA – Quandaries, Reflections & Updates

Copyright © Tony Burfield April 2008. 

QRA – A Potted History 

The Qualitative Risk Assessment (QRA) methodology was recommended as a result of progress of the COLIPA Toxicology Advisory Group and the Joint COLIPA/AISE/EFFA/IFRA Perfume Safety Group, to address dermal sensitisation risk assessment for fragrance ingredients. IFRA adopted this corporate-science derived approach for contact allergens in 2005, when we were informed it was a risk management strategy designed to combat the occurrence of consumer dermal sensitisation, via the restriction of these ingredients in fragranced cosmetic products. This exposure-based system was to be applied across a number of product types grouped into 11 product categories of products (1 to 9 being cosmetic products), setting the concentration limits of individual sensitisers to 'safe levels' for each product category. 

Thus for skin contact, dose per unit area and other considerations could be of primary importance in helping set safe levels of dermal allergens. Information on the QRA system is comprehensively set out in great detail on the IFRA website. The first QRA standards were published by IFRA in May 2006, as part of the 40th IFRA Amendment, and we were told that QRA methodology could be used to set IFRA standards for materials identified as dermal sensitisers where no standards previously existed, or to review the existing IFRA standards. For a while, the old IFRA Standard system would be maintained, whilst industry was getting used to the new QRA system, and making computer reprogramming adjustments etc. 

The first four trialed sensitisers chosen under the QRA system were citral, farnesol, phenylacetaldehyde and tea leaf absolute. EFFA submitted data to the SCCP on citral, farnesol & phenylacetaldehyde, apparently by invitation from the SCCP, who said they needed sensitivity data on IFRA restricted materials to include them in Annex III of the Cosmetics Directive. At the time IFRA restrictions for citral & phenylacetaldehyde were listed in the Inventory part II with quenching proviso’s, but un-noted by the SCCP, IFRA had quietly ditched support for the quenching phenomena (see Cropwatch Review on this topic at http://www.cropwatch.org/newslet8.pdf). Thus the limits for citral under the QRA – IFRA’s 40th Amendment become:

Category	Products	Limit
1	Lip Products, Toys, Insect Repellents	0.04%
2	Deodorants/Antiperspirants	0.05%
3	Hydroalcoholic Products for Shaved Skin, Eye Products, Men’s Facial Cream & Balms, Tampons	0.2%
4	Hydroalcoholic Products for Unshaved Skin, Hair Styling Aids & Sprays, Body Creams]	0.6%
5	Women’s Facial Cream/Facial Make-Up, Hand Cream, Facial masks	0.3%
6	Mouthwash, Toothpaste	1%
7	Intimate Wipes, Baby Wipes	0.1%
8	Make-up Remover, Hair Styling Aids Non-Spray, Nail Care	1.4%
9	Shampoo, Rinse-off Conditioners, Bar Soap, Feminine Hygiene Pads & Liners	5%
10	Detergents, Hard Surface Cleaners, Diapers	2.5%
11	All Non-Skin or Incidental Skin Contact Products	No restriction

Citral distribution amongst some common essential oils is given in IFRA’s 40^th Amendment Appendix 1 Part 1, where you will find values ranging from <90% for lemongrass oils to <0.1% for orange oil sweet (as usual with IFRA, botanical details & geographical origin details are not provided). Similarly, data is presented for farnesol distribution in some natural products.

A pity too, that before EFFA forwarded IFRA’s evidence to the SCCP, they didn’t consider the work of Sanchez-Politta et al. (2007) which indicates that there is little independent peer-reviewed evidence to actually support the classification of phenylacetaldehyde as a sensitiser. It has to be asked therefore, who’s interests are being served here? Certainly not the fragrance industry or the consumer’s. 

Taken overall, we don’t understand why the EU Commission seemingly has a vested interest in furthering the QRA approach, since not all toxicologists support its rationale, and the results from the various animal test protocols which can be used to calculate the EC3 values to predict likely sensitiser potency classifications are often conflicting, such that Dean et al. (2001) correctly surmised that the LLNA test would not correctly identify weak sensitisers or all strong irritants. Further there is very little in the way of aggregate exposure data to support the toxicology, and what there is seems to contradict the predicted classification of sensitizer potency. It is quite possible, from what we have seen so far of the workings of the Cosmetics Commission, that Commission staff themselves are largely are unaware of any other arguments on this subject. Therefore Cropwatch objected to the Regulator (see http://www.cropwatch.org/objectcitral.pdf) that this first use of the QRA methodology did not follow the correct Rules of Legal Procedure Re: Requests for SCCP Opinions in relation to Risk Assessment (C7 2004 D/370235), but we were over-ruled. We also repeated the Storrs argument (Storrs 2007) that DG-Ent/SCCP need to clearly set out & review the basis on which fragrance chemicals have previously been classified as allergens under Directive 2003/15/EC, amending Directive 76/768/EEC, before embarking on any further restrictions (e.g. for citral, farnesol & phenylacetaldehyde). Since only 5 allergens are confirmed as having been the direct cause of clinical allergy, a review of the situation seems imperative. This crucial point has been lost, but Cropwatch predicts, will come back to haunt them, as the rubber-stamping of IFRA's previous opinions on allergens by the SCCP was demonstrably unsafe, as is pretty-well universally acknowledged in the trade. 

In May 2007, the 42nd IFRA Amendment was introduced, to enable the QRA system to be used as a basis to review & redefine IFRA standards set on the basis of dermal sensitisation (16 standards) plus 14 new standards. These were said to cover most of the chemicals currently involved in allergen labeling. Further, as some of these new IFRA standards include ingredients that are present in essential oils and extracts, so these ingredients will also be affected. 

Cropwatch Responds To Bullying

The level of bureaucracy required to enact the QRA approach required that unless perfumes were designed hand-in-hand with software package (such as Formpack), perfumers & formulators would be unable to keep up with the level of calculations required to determine the allowable levels of sensitizers. In early 2007 (15th Jan) Cropwatch started a petition against & announced a boycott of the IFRA 40th Amendment, pointing out that the QRA was creating a hostile environment for the aroma trade, and that the effects of the QRA approach would effectively favour synthetics at the expense of natural aromatics. Cropwatch also alleged discrimination against SME's, since the implementation of this complex approach would make enormously demands on the scarce resources of both small- & micro-organisations. To date, the petition mentioned above has been signed by more than 950, perfumers, natural perfumers, soap-makers, essential oil producers, distributors & users (see http://www.ipetitions.com/petition/ifra40/signatures-20.html), and the petition was eventually presented to IFRA in mid-2007. IFRA did not even have the courtesy to acknowledge receipt of the petition, or to respond in any way, reflecting (in my opinion) the contempt it holds for those who disagree with them. 

Before this, P&F now had started to run a web-poll for votes for and against the QRA issue (see http://www.perfumerflavorist.com/newsletter/5326381.html), and Cropwatch with its massive support from the natural perfumery, essential-oil-using-, soap-making & crafting sectors quickly overwhelmed the poll. Because IFRA was losing heavily (85.1%-14.9%), Jean-Paul Henri, IFRA Director-General, called foul and publicly rapped Jeb Gleason (P&F editor) over the knuckles, so that a grovelling note from Gleason subsequently appeared together with  an accompanying  mail  from Houri (see http://www.perfumerflavorist.com/newsletter/5957641.html). Poll results disappeared from the website & Cropwatch was not invited to put their side of the story - thus history was re-written. In spite of Cropwatch's considerable influence in the perfumery sector, P&F have never printed a single word about Cropwatch activities since (so much for the notion of a free aroma trade press). Louise Prance ran an article on 2nd Mar 2007 for Cosmetics-Design Europe, independently taking the Cropwatch theme that IFRA (exclusively) promotes synthetic ingredients in fragrances, which was hastily taken down, re-written and put-up again, following an objection by Jean-Pierre Houri (Cropwatch has both versions of the article on file). Private correspondence between Houri & Prance has since been circulated amongst aroma trade organisation members (Cropwatch also has a copy of this on file). By the time that Prance had left Cosmetics-Design Europe, Cropwatch was being pilloried on the IFRA website over its opposition to the QRA system (we think this has subsequently been taken down, after Cropwatch claimed that the piece had given us a lot of positive publicity, although there remains a brief mention in IFRA Newsletter Jan 2007). Basenotes invited Burfield and Houri to put their different cases, Burfield bringing up a number of issues at http://www.basenotes.net/columnists/20070223cropwatchvsifra.html. In contrast Houri (not a scientist) chose to give a short propaganda piece about IFRA's policy, its connectivity, its power & importance, not answering any of the specific issues raised (see http://www.basenotes.net/columnists/20070223cropwatchvsifra.html). 

New Developments

In a curious out-of-character move, EFFA have suddenly presented the Schnuch opinions to DG-Enterprise, for labeling requirements for 10 allergens of the notorious ‘26 allergens’ to be reconsidered, on the grounds that in trials, these ingredients rarely present as allergens and in three cases, have not presented at all (Schnuch et al. 2007, Schnuch 2005). This is hardly new; Cropwatch have been imploring the EU Commissioners to look at the Schnuch findings from July 2004 (pub. 2005) for 4 years. These misclassified ingredients are identified (Schnuch et al. 2007) as benzyl alcohol, benzyl benzoate, methyl heptine carbonate, hexyl cinnamal, anisyl alcohol, linalol, benzyl salicylate, amyl cinnamal, limonene & a-methyl ionone (see http://www.cropwatch.org/Cropwatch Claims Victory Over 26 Allergens.pdf). Let’s further consider the implications of this strange move by EFFA. Does it mean that EFFA are (at last) at variance with IFRA policy over the 26 alleged allergen situation? Where does the Schnuch evidence leave the QRA approach? (wrecked!). Does this also mean that EFFA are now pressing DG-Enterprise to consider adverse end-user data present in the Schnuch evidence? - this outcome was, of course, previously ruled as inadmissible to Cropwatch by the Regulator in a Brussels meeting in 2007. Or do different rules now apply for EFFA safety evidence submissions, as opposed to Cropwatch submissions? 

The Oko-test results of Schunch et. al (2004) also identified citral and farnesol in the "rarely found as allergens" category, although in a previous paper Schnuch et al. (2004) had found that farnesol was an important allergen. Nevertheless, as mentioned above, EFFA had previously presented evidence to the SCCP that citral & farnesol should be considered allergens under the QRA system. So (considering the less ambiguous citral case) are EFFA supporting some parts of the Schnuch evidence, but not other parts? It’s all very confusing. EFFA have also taken up the several Cropwatch references from the work of Hostynek & Maibach which broadly suggests that the evidence used to classify anisyl alcohol, amylcinnamic aldehyde, linalol, geraniol, citronellol, alpha-methyl-iso-ionone & methyl heptine carbonate as allergens is not sufficiently scientifically robust on which to base legislation. Again this would seem to potentially undermine the position of the QRA, so we have no idea of EFFA’s motives. It also reflects on the undue haste with which the EU Cosmetics Commission is acting these days, pushing industry for results & policies when the science isn’t sufficiently developed & mature to oblige them. 

IFRA in its Information Letter 801 (02.08.2008), are to introduce yet another costly QRA U-turn for industry, under the forthcoming 43^rd IFRA Amendment. Having sold (as a benefit) the fact that under the QRA approach, higher use levels could be introduced for some materials than the current IFRA Standards allow, in the next breath they change their minds, as “increased exposure due to elevated use levels presents a theoretical possibility that certain pre-sensitised individuals might experience an allergic contact dermatitis where previously they had not.” This gets the 2008 Cropwatch Prize for a Statement of the Bleedin’ Obvious, but we are so pleased that IFRA have caught up their thinking with everyone else on this matter. Unfortunately the financial penalty for industry is the re-writing of formulae & the re-programming of computers to re-align to the downwards exposure limits for the 14 new Standards already introduced under the IFRA 42^nd Amendment. 

Conclusions

The general realisation that excessive regulation from IFRA/RIFM, EFFA & the EU is killing aroma industry prospects is leading to increasing technical support for Cropwatch from within the industry itself, & from aroma ingredient end-users. Blinding people with science or using high-tech. methodology such as the QRA for safety testing belies the fact that there are fundamental weaknesses in this safety strategy, and no amount of arrogance & posturing by safety officials can obliterate this. The fact that IFRA are unable to defend the use of key aroma ingredients on a risk/benefits basis, and that the EU Commissioners have allowed excessive precautionary principled policies to dominate their agenda, means that the time is right for a new independent safety authority to come along and sweep these people away. 

References 

Dean J.H., Twerdok L.E., Tice R.R., Sailstad D.M., Hattan D.G. & Stokes W.S. (2001) “OCCVAM evaluation of the murine local lymph node assay. II Conclusions & recommendations of an independent scientific peer review panel.” Regulatory Toxicology & Pharmacology 34(3), 258-273. 

Sanchez-Politta S., Campanelli A., Pashe-Koo F., Saurat J.H. & Piletta P. (2007) "Allergic contact dermatitis to phenylacetaldehyde: a forgotten allergen?" Contact Dermatitis 56(3),171-2. 

Schnuch A., Uter W., Geier J., Lessmann H. & Frosch PJ. (2004) "Contact allergy to farnesol in 2021 consecutively patch tested patients. Results of the IVDK." Contact Dermatitis. 50(3), 117-21. Schnuch A. (2005) Öko-Test, No. 7 (July) 2004, 55 

Schnuch A., Uter W., Geier J., Lessmann H. & Frosch P.J. (2007) “Sensitization to 26 fragrances to be labelled according to current European regulation. Results of the IVDK and review of the literature.” Contact Dermatitis. 57(1),1-10. 

Storrs F.J. (2007) “Allergen of the year: fragrance.” Dermatitis 18(1), 3-7.   

Technorati Tags: qualitative risk assessment,QRA,fragrance ingredients,IFRA,citral,farnesol,phenylacetaldhyde,tea leaf absolute,Cropwatch,bullying,23 allergens,allergens,perfumery

aromatisches Blog - Aromatics Blog

Das aromatische Blog widmet sich den Düften und Wohlgerüchen – dem Parfüm. (The aromatic blog devoted to the scents and smells good - the perfume.)

I've added a new blog to our perfumery blogroll: aromatisches Blog. It's in German, but can be easily translated with Google or other translation software, although the translations are a bit awkward.

Recent posts have discussed Benzyl Acetate (a constituent of jasmine); the difference between Perfume and Cologne; The history of perfume in Greece and mythology; working with crystalline materials; aromatic patchouli; the Berlin Botanical Garden (with plant photos); ESTEBAN patchouli perfume; the history of perfume in the Bible; and some great paintings from 1922 demonstrating that Perfume alone . . . is often not enough . . . you need to have some water.

The blog has been active since July 2007. Note that this blog is not strictly natural perfumery.

The Definition of Natural

UPDATED

At a webinar presented by Perfumer&Flavorist Magazine last month, there was a discussion of the definition of "natural" when used in the natural products industry, which of course includes the natural aromatic products that are the focus of this blog. The webinar grew out of a similar discussion by natural products retail brand owners and suppliers that was featured in a Special Naturals & Organics issue of "GCI (Global Cosmetics Industry): The Business magazine for the Global Beauty Industry," a sister publication of P&F.

It turns out that the "Natural" Products Industry has not yet agreed upon a definition of what "natural" products are. There is reference in both the Webinar and the article referenced above to an effort to develop a "Natural Personal Care Products Standard" being put together by the Natural Products Association (NPA)and to be discussed at their National Lobbying Day to be held in Washington, DC on April 8.  Unfortunately the NPA didn't get their draft up on their website, so we can't link to the specifics. However, there are other definitions of "Natural" in use.

Burt's Bees has a definition posted on their website that is probably the draft, since the Chair of the NPA committee working on the Standard is from Burt's Bees. The draft requires that products labeled "Natural" must "be made with 95% truly natural ingredients, contain no ingredients with potential suspected human health risks, and use no products that significantly or adversely alter the purity/effect of the natural ingredients." "Natural" is defined as "Ingredients that come from a purposeful, renewable/plentiful source found in nature (flora, fauna, mineral) and using "Processes that are minimal and don't use synthetic/harsh chemicals, or otherwise dilute purity."

The standard goes on to define when non-natural ingredients can be used, and then provides a list of ingredients that should never be used, including (of interest to us because of their use in solvent extraction) Petro Chemicals, and finally to list Processes that should never be used: "Ethoxylation, sulfonation, polymerization and unfavorable varieties of quaternization — Industrial processes using caustic solvents that leave residual compounds and impurities that may end up concealed in the final consumer product."

The draft NCA definition is not the only one out there. The International Association of Natural Product Producers (IANPP) has produced two definitions, one for Natural Ingestible Ingredients and another for Natural Topical Ingredients. They are careful to set these definitions in a context that excludes "considerations such as safety, allergies, toxicity, animal testing, socially responsible packaging and business practices (fair trade, third world projects, responsible use and ingredient disposal, cooperative work environment), respect for endangered species, biodegradability/environmental friendliness, environmentally protective methods of production, etc." These, of course, are important, but in their opinion need to be considered separately from the definition of "natural."

The IANPP definition contains similar elements, but differs from the NCA definition in some significant ways:

• It doesn't deal with the issue of allowing a percentage of ingredients to not be natural. 
• It contains a more precise processing limitation: "Any changes to the original natural ingredient must not undergo changes in one or more covalent bonds during manufacturing and/or processing." 
• It requires that "solvents must be found in nature (originate from plant, animal or inorganic mineral sources) and the processing method must not introduce anything that is not of natural derivation" 
• It defines synthetic "as a substance not derived from natural sources with biological and/or accepted food processing/handling techniques 
• It lists acceptable and unacceptable processing methods (of interest to use, the acceptable list includes "cold pressing, ... natural water/alcohol extraction, ... extraction with natural solvents, expeller pressing (oils), steam distillation, [and] supercritical CO2 Extraction...." (ultrasonic extraction is missing from the list). 
• The unacceptable processing method list contains only two items: Gamma Ray Irradiation and Synthetic solvent extraction. 
• [I think they've made an error in their web page--under Gamma Ray Irradiation they list two bullets that seem to refer to preservatives], allowing Preservation by thermal, sound, or photochemical methods including microwave, ultrasound, UV, or infrared) but listing nuclear or thermo-nuclear preservative methods as Not Acceptable. 
• They don't list specific banned chemicals, but instead ban artificial/synthetic "additives, colorings, coloring agents, preservatives, antibiotics, hormones, processing aids, carriers, synthetically derived and/or processed contaminants from packaging, GMO’s or other non-natural ingredients" 
• Require that ingredients be "Be fully disclosed and documented regarding ingredient derivation and method of processing" 
• Include the words “preserved with” on the label regarding preservative ingredients.

As mentioned in the GCI article, there are some other definitions of natural that are being used by some companies. These all need to be integrated together with a public discussion of the issues.  The NPA intends to have a discussion, I'm sure, but so far it hasn't been out on the web where the small companies who may not be members of the NPA can access it.

I don't think either of the definitions discussed here are adequate to become the exact definition used by the industry. They use somewhat different approaches, and both contain elements that ought to be included. More discussion is definitely needed.

UPDATE: An attempt to contact the IANPP resulted in a response indicating that the IANPP has turned its project over to the NAP and that there should be some results by the end of this year.

Furanocoumarins in cosmetics – worrying developments

IFRA IL 799. 

UPDATED to correct abbreviation error.

IFRA have just released an Information Letter (IL 799) on 'Controlling furanocoumarins in citrus & other essential oils', together with a document on FC's in cosmetic products. Ordinary members of the public, and citrus oil end-users who are not members of the requisite professional trade associations, may find this IFRA Information Letter difficult to locate, but essentially the letter notes the following: 

1. That a previous IFRA Standard limits FC's (specifically bergapten) to 15ppm in consumer products for UV-exposed skin.  Cropwatch comments: As far as we can establish, few perfumery companies have ever abided by this IFRA Standard, and a considerable number of individual working perfumers who we have previously contacted remained completely uneducated about FC levels in the aromatic ingredients with which they construct perfume formulae.  Little information either has been publicly available from any citrus product supplier. A recent suggestion by the Cosmetics Regulator (in a communication to EFFA) that FC's in aromatic ingredients can be estimated by HPLC, shows how removed these officials are from any economic & practical reality, and how they continue to only be able to suggest high-technology fixes which economically discriminate against the economic resources of smaller companies. 
2. Entry 358 of Annex II of the Cosmetics Directive prohibits FC's in cosmetics except for any natural presence in essential oils. In sun-protection & bronzing products FC's are limited to 1 ppm. Cropwatch comments: Again there is little evidence that there is any awareness of the universal enactment of this legislation within the EU marketplace.   
3. The SCCNFP Opinion SCCNFP/0392/00 September 25th, 2001 called for a limit of 1ppm of total "furano-coumarins & furano-coumarin like substances" in finished cosmetic products, an imposition which was fifteen times more severe as the existing (& probably little-adhered to) IFRA Standard mentioned above. Cropwatch comments: The SCCP Opinion on Furanocoumarins in Cosmetic Products (SCCP/0942/05), ratified on the 13th Dec 2005 is more recent. As usual, the SCCNFP's/SCCP's spoon-fed comprehension of the ingredient toxicology in both instances was incomplete, and its "experts" did not fully appreciate that not all FC's & "furano-coumarin like substances" necessarily present a photo-carcinogenic risk; indeed some might show photo-protective properties. The Opinion was therefore contemptuously received, as well as being practically unworkable in the absence of clear data showing FC concentrations across the huge range of FC-containing aromatic ingredients in the perfumer’s palette. Not the least, the imposition of such a severe limit for FC's in finished cosmetic products would practically eliminate the use of citrus oils in fragrances, as Cropwatch has previously extensively discussed in its Newsletters over 2006-2007. 
4. According to IL 799, "the industry" (individual company identities withheld), the industry-funded RIFM organisation and the EU Commission have reportedly embarked on a collaboration which has resulted in a Risk Assessment which "was shared with the European Commission at the end of 2007" (public accessibility of this Risk Assessment is unstated). Reportedly, this proposes that for leave-on products, a limit of up to 5 ppm FC's from a combination of any of the 6 following FC markers will be allowed: bergapten, bergamottin, byacanangelicol, epoxy-bergamottin, isopimpinellin & oxypeucedanin. A less restrictive limit of 50 ppm of FC's  for rinse-off products is also proposed. IFRA have suggested that "the Industry", for whom it increasingly seems to be the self-appointed spokesperson, meets DG-Enterprise/DG-Sanco "to explain & discuss its proposals in more detail". Cropwatch comments. The specter of a few un-named megacorporations which are potentially able to finance safety research and thus to dictate areas of EU safety policy is alarming, especially as complex bureaucracy such as that in the above scheme, will advantage the larger aroma concerns, and discriminate against the smaller companies - a worrisome area which could so easily become considered as falling into a restrictive practice.

CONCLUSIONS 

Cropwatch maintains that, as we said before, the case against the photo-toxicity of individual FC’s, as presented in previous SCCP Opinions such as SCCP 09542/05, remains scientifically non-robust, and there is a lack of supporting knowledge, understanding & experimental & technical data. For FC’s occurring in natural aromatic products, matrix effects & the anti-carcinogenic potential of other co-occurring substances remain unclear. Whether any newly presented evidence will instantly clarify this position is uncertain, because although we are supposed to live in a European democracy and there is supposed to transparency in all EU Commission safety policy dealings, key documents relating to safety studies in this area continue to be withheld from the general European public.   

Cropwatch suggests the following to its supporters: 

1. The proposed legislatory conspiracy between unidentified industry concerns, IFRA-RIFM and the EU Commission, to limit FC levels in finished cosmetics for sale in the EU marketplace, is vetoed by the cosmetics & natural products trade in general. This is because the EU Cosmetics regulatory officials have so far failed to clearly & unequivocally establish a robust case of need to control the existing levels of consumer exposure to FC's in cosmetics. 
2. That the lack of transparency in the evidence-submission process surrounding alleged FC toxicity/carcinogenicity data is corrected by EU officials & advisors. This sort of secrecy is not acceptable in a supposedly democratic European society.

It should also be noted that the outfall from the suggested Risk Assessment allegedly submitted by IFRA/RIFM to the EU Commission for its consideration in late 2007, is likely to do little to address the problems of the continued freedom to use certain citrus ingredients in perfumery/natural perfumery. We all know in our heart-of-hearts that the more the larger Aroma Corporations fund the activities of regulatory-centered bodies such as RIFM, IFRA, EFFA etc., the quicker the end will come for unrestricted natural ingredient usage in perfumery.    

Tony Burfield
Cropwatch.

Technorati Tags: IFRA,IL799,FC,furanocoumarin,citrus essential oils,IFRA IL799,SCCNFP/0392/00,SCCP/0942/05,bergapten,perfumery,perfume safety,perfume toxicity

Enviroblog: New York Times seduced by fragrance industry

Enviroblog takes on the New York Times for an article on the fragrance industry and the practice of developing patented fragrance ingredients.  Chandler Burr in The Times compares the fragrance industry to the pharmaceutical industry development of proprietary  drugs such as Lipitor. Enviroblog points out that there are differences, since the FDA regulates the drugs for safety, but the fragrance ingredients are not regulated and the safety/health effects are often unknown. Burr argues in favor of the synthetic fragrances,pointing out that they may cost less and may be used in place of natural ingredients such as rosy ketones that set off allergic reactions at high doses.

Enviroblog argues that the claims of ecological soundness in the Times article are invalid because the perfume and body care ingredients end up polluting the overall ecosystem, citing research that phthalates from fragrance products can affect the reproductive hormone levels of fish. The Times has [mostly] ignored any environmental or safety issues entirely in their article.

For those of us in the natural products industry, the entire argument almost seems outside our purview. Our argument is that natural products are better and safer, and the public seems to be increasingly agreeing with us, or at least the mainstream large corporate cosmetics and fragrance industry perceives that is the way it is, as they are starting to offer more organic and natural products, even as they continue to develop more synthetics. The reality is that we increasingly are living in a world where money and property ownership are taking over. The impact of this in the fragrance industry isn't as great as in, for example, the case of GM Crops or patenting of strains or seeds, because unless we want to get really rich, we have the option of ignoring them and doing our own thing. Even the environmental impact of the bad things in fragrance ingredients is (probably) miniscule compared to the problems of plastic pollution, feedlot pollution, or the causes of global warming. But it all adds up.

The key here is full disclosure of the ingredients and effects, sensible regulation of hazardous or toxic ingredients, and education of consumers, manufacturers, and suppliers about the issues involved. The mainstream media, such as the NY Times, will probably side with the corporate owners of intellectual property, and the blogs, the small indie manufacturers and the natural products users will probably side with the Earth.

I guess I've turned this into a populist issue.  Any comments?

Cosmetic industry bullying & consumer victims

Tony Burfield Feb 2008.

The tendency of powerful corporations to pursue their marketing aims by totally ignoring consumer resistance or preference is becoming a worrying feature of modern society. And instead of taking a neutral stance on controversial safety issues, regulators in the US or EU bureaucracies may well side with the money-makers. We see this, for example, in the FDA’s failure to regulate cosmetic ingredient safety & so protect the US cosmetic & beauty product consuming public, and we see it in the EU Commissions determination to force GM technology on a reluctant Europe, most of which is markedly averse to buying GM products. Indeed on this point the UK is set for a forthcoming battle this year, as BASF attempts to plant GM potatoes for trials in a small field near Cambridge to the considerable annoyance of GM protestors, who will doubtless attempt to wreck the trial, as previously.

In the cosmetics area, the issue of phthalates as unsuitable or hazardous cosmetic ingredients raises the same degree of concern from many cosmetics  consumers as GM products do for food consumers in Europe. The cosmetic industry does not now defend, does not use (because it not allowed to) and keeps very quiet about the former use of those phthalates as diluents for resinoids, essential oils & perfumes – such as DIOP (di-isooctyl phthalate), DNBP (di-n-butyl phthalate), DEHP (di-2-ethylhexyl phthalate) etc. In fact in 2001 the EU passed regulations restricting the use of 6 phthalates (excluding DEP) in children’s products intended for age 0 to 3 years. But industry does continue to arrogantly defend the use DEP (diethyl phthalate) in the face of continued consumer opposition, which it thinks it can brush aside.

Diethyl phthalate (DEP) was given a clean bill of safety by the Cosmetic Ingredient Review Expert Panel (CIR) in 2002, & by the SCCP in 1992 (SCCNFP/0411/01) & in March 2007 – but Cropwatch had established in late 2007 that up to that point, the SCCP was incapable of conducting an independent literature search on any safety issue laid before it. It cannot be ruled out that its “expert” committee wasn’t prone to potentially be spoon-fed skewed or biased information. However that said, evidence of adverse health effects for DEP are pretty sparse. The National Resources Defence Council (NRDC) report on phthalates in air fresheners, & petition to the Environmental Protection Agency (EPA) & Consumer Product Safety Commission (CPSC), was summarily dismissed by the Fragrance Manufacturers Association of the United States (FMA) who, in a statement on Nov 7th 2007, called on the EPA to deny the citizens petition, maintaining that their conclusions on phthalates in air fresheners were ‘baseless & irresponsible’. Sathyanarayana et al (2008) claim to have found phthalates in infant diapers,citing baby care products as possible sources of exposure. Again the FMA have been quick to criticize this study. In an earlier study (TNO 2005), Greenpeace Netherlands commissioned the TNO to analyse 36 perfumes, 35 of which contained phthalates, 34 of which contained DEP, and 19 of which contained DEHP.  The TNO report eliminates the polymer spraying parts of the perfume containers as a source of phthalates.

If it is (now) true that the majority of the fragrance industry does not use phthalates other than diethyl phthalate, it still needs to explain why a range of phthalates often appears in the detailed analysis of perfumes. However in spite of the virtual dismissal of the problem by industry trade associations, many of us who aren’t career toxicologists making second-hand reassurances, but who actually work hands-on within the cosmetic industry, can name a handful of companies who still occasionally use phthalates other than DEP. Further, ingredient processing where molecular distillation employs co-solvents, or leaching from processing & storage containers & pipework, could still prove to be the source of some of these minor phthalate contaminants It is certainly not good enough to for the assemblers of perfumes who manufacture perfume compounds from bought-in ingredients to throw their hands up in the air and say “we’re not guilty.” There is more to the story than this.

Finally, the fragrance manufacturing industry has to face the fact that however safe they may maintain diethyl phthalate to be, consumers don’t want the ingredient in their purchased cosmetics, and they don’t necessarily want to be bullied by industry into having to accept its presence. Ultimately, of course, it may be up to the consumers to buy their cosmetics from manufacturers with a “no phthalates” policy.

References

Sathyanarayana S., Karr C.J., Lozano P., Brown E., Calafat A.M., Liu F., Swan S.H. (2008) "Baby care products: possible sources of infant phthalate exposure." Pediatrics 121(2), 260-268, or available on-line at http://www.pediatrics.org/cgi/content/full/121/2/e260

Scientific Committee on Consumer Products (SCCP), “Opinion on Phthalates in Cosmetic Products," FR/07/69, adopted at its 11th plenary meeting of March 21, 2007. Available online here in PDF format.

TNO-report R&I-A R 2005/011 "Phthalates & Artificial Musks in Perfumes" Greenpeace Netherlands, available online here in PDF format.

Technorati Tags: phthalates,perfume safety,perfume toxicity,fragrance safety,cosmetic safety

Coumarin: The Real Story (Updated Jan. 2008).

Copyright © Tony Burfield 2006-2008
A PDF copy of this paper is available on the Cropwatch web site.

What is it?

Coumarin (2H-1-benzopyran-2-one) CAS No 91-64-5, is a crystalline white solid when seen pure, with a hay-like, sweet aromatic creamy odour with certain nutty shadings, much used in synthetic form as a fragrance chemical for perfumes and for fragranced soaps and detergents. Coumarin has a widespread occurrence in natural products too (see separate section below), and is a representative of the lactones (where a lactone is an ester group integrated into a carbon ring system).

 

References:

BfR (2007) – see http://www.bfr.bund.de/cd/10569

Born S. L., Rodriguez P. E., Eddy C. L. & Lehman-McKeeman L. D. (1997) “Synthesis and reactivity of coumarin 3,4-epoxide.” Drug Metabolism and Disposition 25, 1318-1323.

Carlton B. D., Aubrun J-C. & Simon G. S. (1996) “Effects of coumarin following perinatal and chronic exposure in Sprague-Dawley rats and CD-1 mice.” Fundamental and Applied Toxicology 30, 145-151.

Cohen A.J. (1979) “Critical Review of the toxicology of coumarin with special reference to interspecies differences in metabolism and hepatoxic response & their significance to man” Food Cosmet. Toxicol. 17, 277-289.

Fentem J. H. & Fry J. R. (1991) “Comparison of the eˇects of inducers of cytochrome P450 on Mongolian gerbil and rat hepatic microsomal monooxygenase activities.” Xenobiotica 21, 895-904.

Floc’h F. (2002) “Coumarin in Plants and Fruits: Implications in Perfumery.” Perf. & Flav. 27 (Mar/Apr 2002), 32-36.

Givel M. (2003) “A comparison of US and Norwegian regulation of coumarin in tobacco products.” Tobacco Control 12, 401-405

Hadidi H., Zalsen K., Idle J.R. & Cholerton S. (1997) "A single amino acid substitution (Leu160His) in Cytochrome P450 CYP2A6

IKW (2008) – see http://www.ikw.org/pages/prodgr_details.php?info_id=304&navi_id=km&subnavi_id=aktuelles&page_title=Körperpflegemittel

Kaighen M. & Williams R.T. (1961) "The metabolism of 3-14C coumarin" Journal of Med. Chem 3, 25-43.

Lake B. G., Gaudin H., Price R. J. and Walters D. G. (1992a) “Metabolism of [3-14C]coumarin to polar and covalently bound products by hepatic microsomes from the rat, Syrian hamster, gerbil and humans.” Food and Chemical Toxicology 30, 105-115.

Lake B. G., Osborne D. J., Walters D. G. and Price R. J. (1992b) “Identification of ohydroxyphenylacetaldehyde as a major metabolite of coumarin in rat hepatic microsomes.” Food and Chemical Toxicology 30, 99-104.

Lake B.G., Gray T.B.G., Evans J.G., Lewis D.F.V., Beamand J.A. & Hue K.L. (1989) "Studies on the mechanism of coumarin-based toxicity in rat hepatocytes: comparison with dihydrocoumarin and other coumarin metabolites.” Toxicology & Applied Pharmacology 97, 311-323.

Lake B.G. (1999) “Coumarin Metabolism, Toxicity & Carcinogenicity: Relevance for Human Risk Assessment.” Food & Chemical Toxicology 37(4), 423-453.

Lake B.G., Gray T.J.B. (1999) "Studies on the mechanism of coumarin-induced toxicity in rat hepatocytes: Comparison with dihydrocoumarin and other coumarin metabolites." Toxicology and Applied Pharmacology 97(2), 311-323.

Norman R. L. & Wood A. W. (1984) “o-Hydroxyphenylethanol, a novel lactone ring-opened metabolite of coumarin.” Drug Metabolism and Disposition 12, 543-549.

Steensma A., Beamand D.G., Walters D.G. et al. (1994) “Metabolism of Coumarin and 7-ethoxycoumatrin by rat, mouse, guinea pig, Cynomolgus monkey & human precusion-cut liver slices” Xenobiotica 24, 893-907.

Vocanson M., Goujon C., Chabeau G., Castelain M., Valeyrie M., Floc’h F., Maliverney C., Gard A. & Nicolas J.F. (2006) “The Skin Allergenic Properties of Chemicals may depend on Contaminants” Int Arch Allergy Immunol 140, 231-238

2. The NTEF’s campaign against the coumarin-containing Angel perfume2.

The Las-Vegas based NTEF (National Toxic Encephalopathy Foundation) has received some media attention over allegations that Clarins Angel perfume (Thierry Mugler) contains toxic ingredients causing (amongst others) ocular damage. It appears that NTEF president Angel de Fazio had filed a lawsuit in the District Court in Clark County Nevada against Clarins in October 2004 claiming that one spray of the company's Angel Parfum had left her permanently disabled (Montague-Jones 2007b). The same report reveals that, again allegedly according to Clarin’s legal spokesperson, de Fazio's claims had been dismissed in January 2007, the court ruling “that the allegations were without merit and brought in bad faith. She was ordered to pay Clarins $77,851 in costs, fees and sanctions”.

Earlier, Montague-Jones (2007a) had reported that the NTEF had stated that Angel Parfum fits the FDA definition of a health hazard because it contains the scent coumarin, which it considers to be a dangerous poison. The Aromaconnection blog (www.aromaconnection.org) also reported the story on 12th Nov 2007, informing that the FDA has accepted a petition from the National Toxic Encephalopathy Foundation (NTEF) to have Angel Perfume declared "Misbranded", and had asked that its importation be halted until the issue is resolved. Nina Immers posted a long comment to this carried item (Immers 2007) reeling off some well-known toxicology studies on the potential hazards associated with the uncontrolled use of perfumery ingredients. Searching for any comments relevant to Angel perfume, there is a statement that coumarin is hepatotoxic in mice because it is metabolised to coumarin 3,4-epoxide, which has been linked to tumour formation in rats, and it is claimed that there is evidence that this metabolic route occurs in humans. Although Cropwatch was initially doubtful about the validity of this point, we do think that this area needs to be clarified by further research, to examine whether there is a quantifiable risk to the small number of people that cannot detoxify coumarin by the 7–hydroxycoumarin route, as mentioned elsewhere in this document.

Cropwatch had some previous correspondence with de Fazio in Jan 2007, where we commented that the analysis of Angel perfume available at http://www.national-toxic-encephalopathy-foundation.org/oculartest0001.pdf. was extremely poor and that perhaps Cropwatch could have provided a more comprehensive analysis3. We also asked if any the components allegedly responsible for ocular damage caused by Angel perfume had been identified (actually stated as damage to the cornea), Angel de Fazio indicated (at the time)that this information was not available.

3 You could take the view that Angel by Thierry Mugler (Clarins) has the elements of a chypre fragrance (patchouli-evernyl accord), but more importantly is perhaps the first ground-breakingly successful "gourmand" fine fragrance. It is very sweet, having chocolate, red berry, praline, vanilla & cassis aspects. In a comprehensive analysis, you might expect to find veltol, patchouli, evernyl, hedione, frambinone, vanillin, canthoxal, a cassis base and certain lactones present.

Cropwatch was uncertain why Angel perfume had been particularly identified for criticism since there are fragrances still currently available arguably with higher coumarin contents - for example the original "Joop Homme" (Joop 1989) or "Le Male" (Jean Paul Gaultier 1995). Further, an NTEF press release on Aug 27th 2007 seemed to confuse the actual ingredients in Angel perfume with allergens required to be disclosed by labeling. A further NTEF news release of 27th Oct 2007 by de Fazio that maintaining that coumarin is a harmful perfumery ingredient is supported by Jack D. Thrasher, Ph.D., who is described as a "Toxicologist/Immunotoxicologist/Fetaltoxicologist". Unfortunately almost all the supplied references supposedly supporting the case do not actually concern coumarin at all - they concern coumarins such as warfarin, so Cropwatch can’t see this feature actually contributes anything to the case. Nevertheless Montague-Jones picked up the NTEF suggestion that coumarin affected prenatal development & reported it in Cosmetic-Design (Montague-Jones 2007c), & subsequently the article was circulated to the membership of several perfumery trade organisations. We believe this story, which has nothing to do with coumarin, originates from two studies by Wesseling et al. (Wesseling et al 2000; Weisling et al. 2001) which refer to pre-natal etc. exposure studies to the oral anti-coagulants acenocoumarol, phenprocoumon & coumadin (WarfarinÔ) (“coumarins”), and acenocumarol & phenprocoumarol respectively, all of which are capable of crossing the placenta and may affect the central nervous system. Coumarin however is not an anti-coagulant (Feuer 1974).

To summarise, Cropwatch believes that the NTEF haven’t (yet) made a convincing case that coumarin is a dangerous perfumery ingredient presenting quantifiable risks to cosmetic users.

2.Adapted from the author’s blog posting on www.aromaconnection.org

Coumarin-containing Natural Products.

Coumarin occurs widely in natural products, generally being liberated from the corresponding glycoside (melilotoside) on drying coumarin-containing herb material. Dicoumarol is a microbiological biotranformation product in spoiled Melilotus Clover and other hay products, and its presence in fodder at >10ppm is cause for concern, as it is responsible for fatalities by hemorrhaging in cattle. This is because dicoumarol interferes with vitamin K reductase in the liver and the liver is unable to reactivate vitamin K, which leads to a decrease in vitamin K-dependent clotting proteins. The study of this compound paved the way to the discovery of anti-coagulant drugs such as warfarin.

Coumarin occurs widely in natural products; the following natural aromatic materials are of note:

Some Natural Coumarin Sources	Notes
Anthoxanthum odoratum L. Flouve oil	Both essential oil and absolute produced.
Carphephorus odoratissmus (J.F. Gemel)syn Liatris odoratissima Mich. syn. Trilisia odoratissima (J.F. Gmel.)Cass. Deer tongue or Liatris	1.6% coumarin. Ratio of coumarin: dihydrocoumarin: 2,3 benzofuran in volatile fraction of extract 1:3:20(Appleton & Enzell 1971).
Cinnamomum cassia J. Presyl. Cassia oil	Coumarin 4-11% (Burfield 1999). Coumarin to 8.73% (TNO 1996) Eu Pharm V (2) allows 1.5 to 4.0% coumarin in cassia oil monograph.
Cinnamomum zeylanicum Cinnamon bark & leaf oils	To 0.3%; rarely to 0.7%.
Dipteryx odorata (Aubl.) Wild. & sometimes D.oppositifolia Tonka bean absolute	1-3%, or up to 10% coumarin in tonka beans (Hagers Handbuch 1973); also dihydrocoumarin, o-coumaric acid, ethyl & methyl meliotate etc (Ehlers et al. 1996). Tonka absolute contains up to 65% coumarin
Galium odoratum L. syn. Asperula odorata Woodruff absolute & concrete	Variable; coumarin content develops on drying herb, although headspace of freshly cut woodruff found to be 80% coumarin (Surburg et al. 1993). Used in alcoholic beverage flavourings (e.g. vodka).
Hierochloe odorata (L.) Beauv Sweet grass	Use to flavour vodka in Russia.
Lavandula spp. Lavender & Lavandin qualities.	Lavender absolute to 8.0% coumarin; lavandin absolute to 5.0% coumarin. Spike lavender oil to 0.3% coumarin.
Lolium perenne L. & other spp. incl. Phleum pratense (Timothy grass), Poa pratensis L. (Meadow grass), Cynosurus cristatus (Crested Dog’s-Tail), Anthoxylum odoratum L. and Melilotus spp. Foin oil.	Essential oil and absolute produced. Foin essential oil contains some 8% coumarin.
Melilotus alba Medik. Bokhara Clover, or White Sweet Clover	Less used than Common Melilot (q.v.)
Melilotus officinalis L. (Pallas) Common Melilot or Yellow Sweet Clover	0.9% coumarin on dry weight basis. Wagner (1996) says 0.25-0.45% coumarin in herb, together with umbelliferone, scopolin etc.
Mentha spp. Peppermint oil	20 ppm (TNO 1996)

Table 1: The occurrence of coumarin in some common herbs & natural products.

Coumarin also occurs in trace amounts in the oils of:

Billy Goat Weed Ageratum conyzoides L.
Sweet wormwood Artemisia annua L.
Mugwort Artemisia vulgaris L..
Carrot Seed oil Daucus carota L. ssp sativus (Hoffm.) Arcang.
Champaca Michelia champaca L.,
Narcissus spp.
Clary sage Salvia sclarea L.

Melilotus leaves from Melilotus officinalis L. have been used to flavour snuff & tobacco. Tonka bean absolute, deertongue absolute & melilotus absolute find some uses in perfumery, but woodruff absolute is no longer much used, apart from flavouring wines. Coumarin derivatives such as the sweetly herbaceous 7-hydroxycoumarin (umbelliferone) also occur in natural products (e.g. in lavender absolute from Lavandula angustifolia) but derivatives like herniaren are banned by IFRA.

Coumarin in Flavourings.

Use of coumarin and coumarin-containing herb extracts was common in earlier times. Walter (1916) relates the use of woodruff extract from the fresh flowering herb in the preparation of lemonade, but remarks that it tends to be weak and prone to cause turbidity, and gives an alternative recipe for woodruff flavouring constructed from synthetic coumarin, alcohol and tonka bean tincture. Use of woodruff extract in cola, caramel, gooseberry and other flavourings is also detailed, and the use of tonka essence containing coumarin, vanillin etc is also outlined for flavouring of fondants.

Earlier reports of the toxicity and carcinogenicity of coumarin are now believed to be due to impurities, but coumarin is banned in foods in USA (21CFR 189.130), Japan, India, & the EC, and was banned in Germany from 1970 to 1991 (the ban is now replaced by a concentration limit) etc. Since many derivatives of coumarin are commercial poisons, e.g. warfarin, the well-known rat poison, it has been difficult to persuade people of coumarin’s safety. However a detailed discussion of the beneficial uses of Melilotus extract & coumarin in phytotherapy (and there are many) & any remaining toxicological issues are given in a Meliltotus monograph by Mills and Bone (2000).

The FDA dubiously identified coumarin as a carcinogen in 1954. Subsequent studies initially upheld this opinion, but then disproved it. The net result is that because of the controversy (see elsewhere in this document), it cannot be added to foods (although it is famously naturally present in many, including spices (cinnamon), cherries, apricots, green tea, licorice & strawberries!).

In the EU, flavourings are regulated according to the Articles of the European Council’s Directive on food flavourings. Coumarin was placed in Annex II of this Directive (88/388/EEC) in 1988, which was subsequently amended by 91/71/EEC and implemented into UK national law in the Flavourings in Food Regulations 1992: You might remember, that coumarin had been restricted with respect to its allowable concentration in foodstuffs because of allegations of (non-linear dose related) rat & dog carcinogenicity which occurred at high levels of coumarin administration. These considerations caused the regulators to limit coumarin concentrations in food & beverages to 2 mg/Kg, except for limits for chewing gum (50 mg/Kg), alcoholic drinks (10mg/Kg) & caramel confectionery (10mg/Kg). However the EU Scientific Committee for Food (1997) recommended the lowering the coumarin limit to the limit of detection in food, (then 0.5 mg/Kg). However, we know that the metabolism of coumarin proceeds through a different major route of 7-hydroxylation in humans compared with the 3-hydroxylation pathway in rats (Cohen 1979, Fentem & Fry 1993, Kaighen & Williams 1961, Lake et al 1989), further species to species differences being investigated for example by Fenton & Fry (1993), who found that a hepatotoxic route involving 3-hydroxylation and involving a 3,4-epoxide occurs in the rat, but not in baboons, gerbils, some strains of mice, and man. This hypothesis had also been muted by Steensma (1994) amongst others, and was further explored in Lake's paper with Gray (1999), who fed dihydrocoumarin to rats (which cannot form the 3,4 epoxide metabolite) and found no hepatocarcinogenic effect. As was discussed in detail earlier in this document, the existence of genetic polymorphism in humans with regard to the existence of different metabolic detoxification routes for coumarin has brought us to a situation where EFSA has recommended at TDI for coumarin of 0-0.1 mg/Kg body weight.

Coumarin in Perfumery.

Coumarin has a history of importance in perfumery, being the first synthetic (synthesised by W.H. Perkin 1868) to be used in a fragrance - Fougère Royale (Houbigant), where coumarin was combined with lavender, citrus and woody notes.- and since that time coumarin has been fundamental to the fougère perfumery accord, together with lavender and bergamot oils. Synthetic coumarin is used in large volumes in fragrances.

Coumarin has been approved for perfumery use, but was identified as a fragrance allergen by the SCCNFP/0017/98, although many perfumery professionals have refused to believe that pure coumarin is an allergen (see below). Coumarin has been regulated within the 7th Amendment of the Cosmetics Directive (76/768/EEC) such that coumarin requires labeling if present at concentrations of >10ppm in fragrances leave on products, or >100 ppm in fragranced products washed off the skin. Floc’h et al. (2002), Vocanson et al. (2006) & Vocanson et al. (2007) have published data supporting their view that pure coumarin is not a sensitiser, but rather it is impurities that elicit any alleged reaction (see below), an opinion which is widely accepted by the technically-minded in industry, but not, apparently, by the SCCP.

Coumarin as a Sensitiser (?).

An article by François Floc’h et al. (2002), of Rhodia Perfumery & Specialities, looked at pure coumarin applied in homogenous form to the skin of animals and humans, and concluded that coumarin is not a dermal allergen. Coumarin was one of the items you will remember cited in the SCCNFP position paper for Fragrance Allergy in Consumers (SCCNFP/0017/98 final Dec 1999) as being a skin sensitiser, this being the conclusion of previous COLIPA and RIFM opinions. Previous work by Malten K.E. et al. (1984), De Groot A.C. et al. (1988), Larsen W. et al. (1996), and Van Joost T et al. (1985) on coumarin was also reviewed by François Floc’h et al. who commented, amongst other things, on the lack of scientific rigor, and found no statements of the purity of the materials previously used, and who questioned the homogeneity and the stability of the coumarin in petrolatum suspension. Floc’h et al. further indicated the above work failed to distinguish allergy to coumarin and cross-reaction to allergens for which coumarin might be an indicator.

The SCCP Opinion on coumarin as a sensitiser SCCP/0935/05 (adopted 20th June 2006) considers whether coumarin of >99.99% purity had any sensitising properties (industry claims that it doesn’t), & if it doesn’t, whether the Opinion on Fragrance Allergy SCCNFP/0017/98 would need to be changed. The committee concluded that coumarin of 99.9% purity when patch tested at 2% would be able to elicit allergic contact reactions in humans.

A further published paper from Vocansen et al. (2007) on the non-allergenicity of pure coumarin, indicates that dihydrocoumarin, an contaminant of impure coumarin, promotes cell proliferation in the LLNA test whereas pure coumarin does not. The authors state that “that pure coumarin is endowed with very weak sensitizing capacities, if any, and suggest that the presence of contaminants in coumarin preparations may account for the previously reported allergenic properties of coumarin.” All we need now is for the SCCP policy on this issue to come in line with the available evidence (don’t hold your breath).

Cropwatch Comments (from July 2006).

Although the SCCP Opinion heavily criticises various published papers/abstracts/posters by Vocanson et al. (2006), Masamoto (2001), CIT (2001) & INSERM (2003/2004) on regarding alleged coumarin sensitisation on various grounds (i.e. is confusing, there is lack of evidence etc.), those very same remarks apply to their own Opinion. The SCCP document is poorly laid out with lack of clear headings, so that it is not immediately apparent what study you are reading about (until the reader has gone over the paper several times). [The key to understanding the Opinion is that new evidence is considered under various headings: Patch testing, Animal data & LLNA (local lymph node assay) studies, with the identity of the study under consideration confusingly set out in normal type face towards the right hand margin at the bottom of the relevant text (instead of as a heading at the top)]. The discussion 3.3.14 needs rewriting with clear references to the work they are criticising.looks half finished – sloppily, the Vocanson et al. paper is not fully referenced (full details below)

The SCCP Opinion that coumarin of 99.9% purity when patch tested at 2% would be able to elicit allergic contact reactions in humans, seem to us to be largely based on the findings of the study by Vocanson et al. (2006), who claim that they found a reaction of only one subject in 512 hospital patients to pure coumarin (although, on a quick read-through, the SCCP Opinion seemingly only accounts for 510). Commercial samples of coumarin with coumarin derivatives as impurities were found to be weak or moderate sensitisers by the Vocanson team. The SCCP seems to have seized on this one reaction and on the reaction of an individual positive from 101 patients positive to the fragrance mix (of which coumarin is not a component) as evidence that coumarin is a sensitiser. Crucially, the discrepancy between the Vocanson team’s finding of one positive and the SCCP’s reading of two positives is not explained, and presumably the SCCP did not bother to contact the authors for an explanation of why they had dismissed one of these positive reactions.

The SCCP wastes our time reporting on the evaluating an abstract by Masamoto (2001) and concludes, unsurprisingly, there is not enough evidence presented. The SCCP do not provide an explanation of why they were unable to obtain the full paper (maybe they are unable to cope with articles written in Japanese ?).

Cropwatch can only conclude the following:

1. That this SCCP Opinion SCCP/0935/05 only further establishes that the evidence for pure coumarin as a sensitiser is extremely weak. The SCCP defended their previous Opinion on coumarin only by nit-picking at the paper by Vocanson et al. (2006).

2. That criticism by the SCCP of the determinations of the purity of coumarin presented in the publications considered is a bit rich, considering Floc’h’s remarks (Floc’h 2002) that previous work up by Malten KE et al. (1984), De Groot AC et al. (1988), Larsen W. et al. (1996), and Van Joost T et al. (1985) had not paid any/sufficient attention to the issue. If the SCCNFP themselves had looked at the coumarin purity issue more closely in the first place, they would not have classified coumarin as a sensitiser in SCCNFP/0017/98 final Dec 1999.

3. We feel that the SCCP are now adopting a different set of evaluative criteria towards new submitted evidence on coumarin, in order to make judgments that support their previous Opinions – clearly they are being defensive rather than objective.

4. If the SCCP had contacted the authors of the papers on coumarin sensitisation that they were reviewing in SCCP/0935/05 for clarification/further information, it is probable that a different outcome would have resulted. The fact that this was not done has to be seen as having a political dimension.

5. The matter of whether it should be required by law that coumarin – a weak sensitiser at best - should need labeling as required under the 7th Amendment to the Cosmetics Directive, now needs investigation by Judicial Review. Further, the assumption that natural botanical products which contain coumarin are sensitising also needs reviewing; deertongue incoloure (which has a high coumarin content) was after all, previously reported non-sensitising by RIFM (Opdyke D.L.J. 1976)

References.

Appleton R.A. & Enzell C.R. (1971) “Triterpenoids & aromatic components of deer tongue leaf” Phytochemistry 10, 447-449.

CIT (2001): CIT/Study No. 21214 TSS/RhodiascentTM Coumarine/Rhodia Services – RSP 13 Dec 2001

Cohen A.J. (1979) “Critical Review of the toxicology of coumarin with special reference to interspecies differences in metabolism and hepatoxic response & their significance to man” Food Cosmet. Toxicol. 17, 277-289.

Clarke G.S. (1995) “Coumarin” Perf & Flav. 20, (Nov/Dec 1995) 23-34.

de Groot, A.C. et al. (1988) “Allergens in Cosmetics” Arch. Dermatol. 124, 1525-1529.

Ehlers D. et al. (1996) “Reducing the coumarin content of tonka bean extracts using supercritical CO2.” Int J. Food Sc & Techn 31, 93-95.

Felter S.P., Vassallo J.D., Carlton B.D. & Daston G.P. (2006). “A safety assessment of coumarin taking into account species-specificity of toxio-kinetics”. Food & Chem. Toxicol. 44, 462-475.

Fentem J. H. and Fry J. R. (1991) “Comparison of the e€ects of inducers of cytochrome P450 on Mongolian gerbil and rat hepatic microsomal monooxygenase activities.” Xenobiotica 21, 895-904.

Feuer G. (1974) “The metabolism & biological actions of coumarins.” Progress in Medicinal Chemistry 10, 85-158.

Floc’h F. (2002) “Coumarin in plants and fruits: implications in perfumery.” Perf. & Flav. 27 (Mar/Apr 2002), 32-36.

Feuer G (1974). “The metabolism & biological actions of coumarins.” Progress in Medicinal Chemistry 10, 85-158.

Immers N. (2007) http://www.aromaconnection.org/2007/11/ntef-attacks-an.html#comments

INSERM U503/Société Rhodia Services. “Evaluation du potential de sensibilisation cutanée des coumarines à l’aide du Local Lymph Node Assay murin.” 10th Dec 2003/26 mai 2004.

Kaighen M. and Williams R. T. (1961) The metabolism of [3-14C]coumarin. Journal of Medicinal Chemistry 3, 25-43.

Lake B.G. (1999) “Coumarin metabolism, toxicity & carcinogenicity: Relevance for human risk assessment.” Food & Chemical Toxicology 37(4), 423-453.

Larsen W. et al. (1996) “Fragrance contact dermatitis. A worldwide multi-centre investigation (part 1).” Am. J. of Contact Dermatitis 7, 77-83.

Malten K.E. et al. (1984) “Reactions in selected patients to 22 fragrance materials” Contact Dermatitis 11, 1-10.

Masamoto Y. (2001) “Sensitisation & cross-reaction of simple coumarins.” Yagugaku Zasshi, 121, 97-103.

Mills S. & Bone K. (2000) Melilotus monograph in Principles & Practice of Phytotherapy Churchill Livingstone 2000 pp 463-489.

Montague-J