the aromaconnection blog

One More Time: There Are No FDA Certified Pure Therapeutic Grade Essential Oils, Part I

I thought we had cleared up this misconception years ago, however, it seems there are a number of essential oil purveyors claiming to carry essential oils  that are specifically certified as therapeutic grade by the FDA and show this seal below as proof.  Don’t be fooled.  They are not telling the truth.  In reverse order, this is one path to their deception.

 This last trademark has been registered (as a word mark) by DoTERRA Holdings, LLC, 370 W. Center Street,  Orem, UT 84057.  Filed on March 4, 2009, published for opposition on July 1, 2009 and official registration granted on October 6, 2009.  This registration has the disclaimer, “No claim is made to the exclusive right to use ‘certified pure therapeutic grade’ apart from the mark as shown.

A third trademark has been registered (as a word mark) CPTG Certified Pure Therapeutic Grade also by DoTERRA Holdings, LLC, 370 W. Center Street,  Orem, UT 84057.  Filed on March 4, 2009, published for opposition on July 14, 2009 and official registration granted on September 29, 2009. This registration also has the disclaimer, “No claim is made to the exclusive right to use ‘certified pure therapeutic grade’ apart from the mark as shown”. There is a long list of products shown to be associated with this word mark.

A second trademark has been registered (as a word mark) CPTG also by DoTERRA Holdings, LLC, 370 W. Center Street,  Orem, UT 84057.  Filed on March 31, 2008, published for opposition on June 10, 2008 and official registration granted on May 9, 2009.

A first trademark has been registered (as a word mark) CPTG also by DoTERRA Holdings, LLC, 1145 South 800 East, Ste. 134,  Orem, UT 84057.  Filed on March 31, 2008, published for opposition on June 10, 2008 and official registration granted on May 9, 2009. Under the trademark registration, they show application to the following products: Essential oils; Essential oils for household use; Essential oils for personal use; Lavender oil; Massage oil; Massage oils; Natural essential oils; Aromatherapy oils; Bath oils; Body oils; Cosmetic oils; Cosmetic oils for the epidermis; Essential oils for flavoring beverages; Essential oils for food flavorings; Essential oils for use in manufacturing of gelcaps and other dietary supplements; Essential oils for use in the manufacture of scented products; Oils for cleaning purposes; Oils for toiletry purposes; Skin and body topical lotions, creams and oils for cosmetic use; Food flavorings prepared from essential oils; Oils for perfumes and scents; Peppermint oil; Perfume oils; Tanning oils.

DoTERRA, LLC is yet another multi-level marketing natural products company based in Utah who has applied through the U.S. Patent Office to “own” (exclusive use) a registered word mark.  This registered word mark has not been provided to them by the FDA as they claim and is meaningless in proving that an outside certifying body has declared or designated that DoTERRA’s essential oils are certified pure therapeutic grade.  DoTERRA, LLC owns the right to exclusive use of the mark (however not the exclusive right to the actual words “Certified Pure Therapeutic Grade” which is revealing)  This seal or word mark is nothing more than a commercial trademark that they have registered and paid a fee for.  However, DoTERRA is purposefully misinforming potential customers and down liners by email by claiming FDA approval and that the FDA has provided them with the label that they, themselves registered and own.  The FDA does NOT certify the quality of essential oils by therapeutic grade and they do not provide a certifying label as claimed.  Following is an email from DoTERRA sent to a potential customer:

---------- Forwarded message ----------
From: dōTERRA Member Service <service@doterra.com>
Date: Mon, Nov 16, 2009 at 5:01 PM
Subject:  
To: Recipient Name and Email Removed for Privacy

Dear Recipient Name Removed for Privacy,

We apologize if one of our consultants has mislead you in anyway (sic).  All of our oils are FDA approved as being Certified Pure Therapeutic Grade (CPTG). DoTERRA's, CPTG essential oils are 100% pure natural aromatic compounds carefully extracted from plants.  They do not contain fillers or artificial ingredients that would dilute their active qualities and are free of contaminants such as pesticides or other chemical residues.  All of our products are taken through a series of tests including  AFNOR and ISO standards for purity, and all of our manufactures must maintain a GMP certification.  Therefore, we are passing government regulations.  The FDA has provided us with the label of CPTG. We hope we have resolved your concern.

Member Services
doTERRA International, LLC
370 West Center Street
Orem, Ut 84057
800-411-8151
service@doterra.com

Clearly this company is misleading people by claiming that they have a designation and approval provided to them by the FDA that in my expert opinion simply does not exist.  Stay tuned for part II of this series which will focus on FDA regulations that actually apply to essential oils and the part III will provide you with questions to ask a supplier that will ascertain their knowledge of essential oils and expertise in the industry.  

We at Samara Botane and many others in the essential oil trade have are dismayed about the misrepresentation of facts surrounding essential oils that occurs here in the United States, especially within the multi-level marketing industry.  We encourage people to diligently research any essential oil company before choosing them as a supplier.

Marcia Elston
Samara Botane/Nature Intelligence
http://www.wingedseed.com 

Please feel free to repost this message in its entirety, unedited, on your blog as well as social media outlets and newsgroups. 

Notes & News

A new lemongrass variety “suwarna” has been developed by the Central Institute of Medicinal and Aromatic Plants to address drought conditions with a limited amount of planting material released in Uttar Pradesh.  This new variety will produce about 200 kg of oil per hectare as compared to normal varieties that produce about 100-124 kg per hectare. This is an attempt to diversify the income of farmers, particularly those in drought-affected areas.

The International Aloe Science Council presents a scientific primer on aloe. IASC has assembled a comprehensive document exploring the different varieties of aloe, their health properties, cultivation techniques and more. Download this e-book to learn about:

• commonly traded aloe species primarily used in the nutrition industry, and key components;
• cultivation considerations;
• aloe vera as a market commodity, including pricing information;
• a detailed appendix on aloe species; and
• details on requirements for organic certification.

The International Fragrance Association (IFRA) has appointed Aurore Boudet scientific and regulatory affairs manager. She will focus on the management and implementation of the IFRA code of practice, IFRA standards, and the compliance program.

The Research Institute for Fragrance Materials (RIFM) has formed an environmental adjunct group to support the expert panel’s efforts in environmental assessment of fragrance materials and development of IFRA Environmental Standard.  The group includes Michael McLachlan, professor of analytical environmental chemistry, Stockholm University, Sweden, and Beate Escher, deputy director of the national research centre for environmental toxicology, University of Queensland, Australia.  These appointments bring expertise in advising RIFM, especially  in the areas of environmental fate and bioaccumulation.

We at aromaconnection want to remind our community to support an outstanding nonprofit effort: United Aromatherapy Effort (UAE), headed up by Sylla Sheppard-Hanger, was founded in 2001 to support emergency and disaster relief workers by providing rejuvenating aromatherapy and massage services during long and arduous rescue efforts after 9-11.  The group continues to solicit aromatherapy supplies and monetary donations to provide support to U.S. troops in Afghanistan.  We urge you to visit the UAE website to learn how you can contribute.

Traditional Herbal Medicine Under Threat in the United Kingdom

Cropwatch has posted [PDF] and sent out by e-mail to its subscribers an emergency mailing about the situation in the United Kingdom with respect to regulation of herbal medicine. Although this blog is more focused on the aromatics world, we also are interested (and believe our readers are also) in herbal medicine, and at this point it’s not clear to us whether essential oils could or would be included in that regulation.

Most of the readers of this site are Americans, but if you happen to be from the United Kingdom, the EU, or even are American, you should get more information on this issue from the Cropwatch site and sign the petitions linked from it and also linked from the beginning of the Cropwatch letter posted here (emphasis mine):

The purpose of this Cropwatch emergency mailing is primarily to ask
all of you to seriously consider signing the Save Our Herbs petition at http://www.gopetition.com/petitions/support-herbal-medicine.html This organisation not only campaigns on behalf of the general public, but also represents a very significant proportion of medical herbalists of both Eastern and Western traditions, practising in the UK.

Time is very short - if you want to support this very worthy campaign
ensuring the continued availability of safe Herbal Medicinal Products,
the continued free use of a wide range of our safe endemic &
imported Herbs by ordinary people according to our traditions,
preventing the takeover of small Herbal Medicine Suppliers by
pharmaceutical concerns, & opposition to Statutory Regulation of
Herbalists, you will need to sign the petition by 31st October 2009.
The Save Our Herbs campaign’s official website can be found at
http://www.saveourherbs.org.uk/index.html and provides a wealth of
background information to this potential crisis for Herbal Medicine.
Cropwatch strongly recommends you to read through the
comprehensive information to be found there.

The Newsletter continues for 11 pages and will not be reprinted on this blog. But I strongly recommend that you read it and the information on the linked sites and follow through as best you can. You can read the full newsletter here on the Cropwatch site.

Technorati Tags: herbal medicine,UK Regulation,Health Freedom

Cropwatch Newsletter 16: Disproportionate Reactions to Health & Safety Issues

Cropwatch Newsletter 16 has been received by email subscribers. Contents include the following:

• DEFRA vs Georgina Downs
• IFRA & Transgressors
• Robertet Reveals its Evidence on Melissa oil
• Safrole & Human Carcinogenicity?
• EU Commission’s Proposals to Limit FC’s in Cosmetic Products
• Cropwatch’s Letter Objecting to EU Proposals on FC’s Limits
• Save Our Herbs Campaign: Press Release/Website.

It’s also available online in pdf format.

Note that you can sign up on the Cropwatch website to receive their newsletters via email, usually a few days in advance of their online posting. Several of the articles in the Newsletter were previously posted on this blog, but there is a lot of additional information available in the Cropwatch Newsletters.

Technorati Tags: Cropwatch,Cropwatch Newsletter

Safrole: Human Carcinogenicity Risk Over-Stated?

Copyright © Tony Burfield September 2009.

Updated to include additional references 9/19/2009

Preamble

It almost borders on the heretical, perhaps, to suggest that the risk of human carcinogenicity from exposure to dietary safrole has been over-estimated over the years by some toxicologists, and that the existing national & international restrictions on safrole-containing ingredients & end-products can be seen as over-precautious. Weighing the evidence, a convincing case can be made that the human carcinogenic potential of safrole, if not quite negligible at low doses, is considerably less than that of ethanol (Duke 2002). As it is, the existing evidence for the carcinogenicity and genotoxicity of safrole mainly rests on a battery of experiments performed 30-40 years ago, on laboratory rodents dosed with high levels of safrole, where electrophilic metabolites generated by P450 enzymes and sulphurotransferases are identifiable as being responsible for the genotoxicity (see Cropwatch’s extensive Safrole Bibliography at http://www.cropwatch.org/Safrole Bibliography.pdf). Different expert judgments have been made about the risk to humans from alkylbenzenes such as safrole, methyleugenol & estragole, and indeed on the relative importance for human cancer of low-dose exposures to synthetic chemicals generally (Gold et al. 1992). More insight into bioactivation of these (alkylbenzene) compounds in humans has been said to be required to interpret animal data to the human situation (Jeurissen 2007).

Safrole (4-allyl-1,2-methylenedioxybenzene; CAS No. 94-59-7) is known to occurs in the following natural products:

• Chinese Angelica (Angelica sinensis L.)
• Betel oil (Piper betle L.)
• Brown & yellow camphor oil (fractions of Cinnamomum camphora L.) Yellow oil to 20%; brown oil to 80%.
• Cangerana oil (Cabralea cangerana Saldanha)
• Cinnamon leaf oil & bark oils (Cinnamomum zeylanicum Blume) both to 2%
• Kuromoji oil (Lindera spp.) to 12%
• Mace oil (Myristica fragrans Houtt.) to 2%
• Mango ginger oil (Curcuma amada Roxb.) to 9.5%
• Nutmeg oils [E.I. & W.I.], butter & oleoresins (Myristica fragrans Houtt.) E.I, to 2%; W.I. to 0.3%’
• Pepper oil, black (Piper nigrum L.)
• Piper auritum HBK oil to 90%
• Sassafras oils, bark of roots, infusions of roots (Sassafras albidum (Nutt.) Nees to 95%.
• Sassafras oil Brazilian: Ocotea pretosia (Nees) Mez, to 92%
• Star Anise oil (Illicium verum Hook f.)
• Ylang-ylang oils, absolutes (Cananga odorata (DC) Hook. f et Thoms ­subsp. genuine)

…as well as in several other Cinnamomum essential oils (C. burmanni; C. porrectum; C. rigidissum etc.). It also in occurs in witch-hazel (Hamamelis viginiana L.), hoja santa leaves (Piper auritum HBK) and in other natural herbal & spice products & preparations.

Safrole is currently classified as a carcinogen category 2 and mutagen category 3 in the IFRA-IOFI labeling manual 2009. Since out of the three alleged human carcinogens: safrole, estragole and methyl eugenol, safrole is arguably the weakest (see below), these classifications seem somewhat arbitrary.

Substance	Hazard symbol	Risk phrases	Carcinogen category	Mutagen category
Safrole	T	R45-22-68	2	3
Estragole	Xn	R22-40-43-68*	3	3
Methyl eugenol	Xn	R22-40-68*	3	3

Classification of some Carcinogens & Mutagens according to the IFRA-IOFI Labelling Manual 2009

[*Thanks to Penny Williams of Formpak Ltd. for drawing our attention to this labeling issue; further implications over R68 status for estragole & methyl eugenol affecting common essential oils such as Aniseed, Bay, Basil, Fennel and Pine Oil Yarmor, are discussed at http://www.formpak-software.com/active/2009/09/estragol-methyl-eugenol-r68/].

Previously the IARC had surmised that safrole was “Reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity in experimental animals” (IARC 1976); but that “No adequate human studies of the relationship between exposure to safrole and human cancer have been reported” (- IARC 1976). The weak potency of safrole as a carcinogen is illustrated by the fact that level of safrole in the diet of rats necessary to elicit liver tumors ranges from 0.5% to 5.0% (Patri et al. 2002). The TD₅₀ for safrole in rats was found to be 440mg/Kg/d (Gold et al.) compared with 51mg/Kg/d for mice. This compares with a TD₅₀ value for methyl eugenol of 20mg/Kg/d for rats and 19mg/Kg/d for mice. However the TD₅₀ for the proximate carcinogen 1’-hydroxysafrole was found to be 18mg/Kg/d for rats compared with 71 mg/Kg/d for mice.

The hazardous dose of sassafras oil for humans (which typically contains 80% safrole) has been put at 0.66 mg/Kg, based on experimental animal data, and a safety factor of x100; this is claimed to be way- exceeded by imbibing a standard portion of sassafras tea which has been estimated to give a dose of 3mg/Kg for a 60Kg man (Bisset 1994; Segelaman 1976). By comparison Levy (Levy undated) gives a figure of 20 ppm safrole content of root beer before the sassafras FDA prohibition, approximating to a 5mg dose for an 8oz serving. Safrole-free extracts of sassafras have been approved by the FDA for food flavouring use, but apart from being organoleptically inferior, it is also of note that safrole-free extracts of sassafras have produced malignant mesenchymal tumors in laboratory rats (Benedetti et al. 1977).

Safrole & sassafras oil were banned as food & flavouring additives by the FDA on 3^rd Dec 1960 (FDA Ban 21 CFR 189.180; revised April 1 2008), the ban now includes isosafrole & dihydrosafrole (the latter not being known in nature), & sassafras root bark, but in practice both sassafras oil and bark are still widely available in the US, from health food stores and internet suppliers. Safrole appears in Annex II/360 of the EU Cosmetics Directive EU 76/768, and its concentration is limited to 100ppm in finished cosmetic products (50 ppm for oral/dental use; zero for children’s toothpaste). IFRA prohibits the addition of safrole to fragrances as such, and limits the safrole content of perfumes formulated with safrole-containing essential oils (basil, nutmeg, sassafras, cinnamon leaf etc.) to 0.01% (100ppm) for both skin contact & non-skin contact fragrances. These restrictions have caused a significant problem with certain fragrance styles entering the market place – for example in the deployment of cinnamon & nutmeg ingredients in masculine fougères and spicy masculine notes.

The restriction of safrole to low levels in foodstuffs was originally considered to be a threat to the economic welfare of the nutmeg trade, and so exceptions were made (note that curiously, no such exceptions are ever made for natural ingredients in the cosmetics area, presumably because academic ‘expert’ committees in this field are unable to accurately predict the socio-economic effects of their policies). European Council’s Directive on food flavourings 88/388/EEC, amended by 91/71/EEC and implemented into UK national law in the Flavourings in Food Regulations 1992, limits safrole in foodstuffs to 1ppm, except for foodstuffs containing nutmeg (15ppm) or alcoholic drinks >25% volume alcohol (5ppm) and other alcoholic drinks (2ppm). It is of interest to note that Choong & Lin (2001) analysed 25 soft drinks, including Coca-cola and Pepsi, from supermarkets & convenience stores in Tainan and Pingtung, for safrole and isosafrole contents in 1998, finding 20 out of 25 soft drink samples contained safrole and/or cis-isosafrole and the contents of safrole were up to 3-5 times the use limit of 1μg/mL according to the food additive regulations.

Isosafrole (CAS No. 120-8-1), which occurs as (E)- & (Z)- geometric isomers, is a weak, non-genotoxic rodent hepatocarcinogen, classified as a carcinogen category 3 (IARC 1987) which has been alleged to occur in minor amounts in certain essential oils (such as Chinese angelica oil from Angelica polymorpha Max.), ylang-ylang & nutmeg oil & oleoresin, but Lawrence could not confirm its presence in nutmeg oils (Lawrence 1990), and MAFF have disputed its presence in ylang ylang & sassafras products (MAFF 1996a). However MAFF (1994) found 0.1% to 3.4% isosafrole (av. 0.3%) in 10 analysed samples of nutmeg oil and 0.1 to 2.7% (av. 0.9%) in 3 analysed nutmeg oleoresin samples (origins not disclosed). Since isosafrole usually co-occurs with safrole in certain natural products, at concentrations typically an order of magnitude lower than the safrole concentration (MAFF 1996), it was proposed by MAFF that isosafrole is an artifact formed during the processing of safrole-containing raw materials.

Safrole Metabolism

Intraperitoneal dosing of rats and guinea pigs with safrole produces the following urinary metabolites; 1,2-dihydroxyl-4-allylbenzene, 1'-hydroxysafrole, 2-methylenedioxy-4-(2,3-dihyroxypropyl)benzene, 1,2-dihydroxy-4-(2,3-dihydroxypropyl)benzene, 2-hydroxy-3-(3,4-methylenedioxyphenyl) propanoic acid, and 3,4-methylenedioxybenzoylglycine (Stillwell et al. 1974). Two pathways have been proposed whereby hepatotoxic substances are produced from safrole (Dietz & Bolton 2007). The first proceeds via the P450 catalyzed hydroxylation of safrole to 1'-hydroxysafrole, and its subsequent conjugation with sulfate to produce a reactive sulfate ester, which creates creates a highly reactive carbocation via a SN1 displacement, which alkylates DNA. The second pathway involves the formation of hydroxychavicol via the P450 catalyzed hydroxylation of the methylenedioxy ring of safrole, which is subsequently oxidized to an o-quinone, which non-enzymically isomerizes p-quinone methide. Dietz & Bolton (2007) consider that these experiments by Bolton et al. (1994), Miller et al. (1985), Boberg et al. (1983), Daimon et al. (1997-1998) & Jeng et al. (2004) and the in vitro & in vivo experiments of Luo & Guenthner (1997), Gupta et al. (1993), Randerath et al. (1993), Daimon et al. (1998) & Daimon et al. (1997) prove the genotoxic effects of safrole and justify the regulatory action of the FDA & other authorities. Cropwatch takes issue with this conclusion; the mere existence of pathways in rodents fed high levels of dietary safrole which give rise to certain hepatotoxic substances does not, of itself, prove the potential for human carcinogenicity under normal living circumstances.

Although small amounts of safrole (0.63mg/Kg) have been shown to be cleared almost completely from the body within 24 hours in man & rats (Benedetti et al. 1977), the main urinary metabolite of safrole dosed in larger amounts is 1,2-dihydroxy-4-allylbenzene in both rats & man; 1’-hydroxysafrole and 3’-hydroxyisosafrole were also detected in the urine of the rat, but not of man (Benedetti et al. 1977). Jeurissen (2007) has identified the human P450 enzymes involved in the 1’-hydroxylation of safrole, where important roles for a series of enzymes via a series of in vitro experiments were postulated. Lifestyles factors which may lead to poor or extensive metaboliser phenotypes, which either reduce or increase the relative carcinogenicity risk, were discussed.

Also compelling evidence for humans, perhaps, lies with studies made of habitual quid chewers of betel & areca nut, where a constant body-loading of safrole may give rise to tumors over an extended time period. In particular, inflorescences of betel have been shown to contain relatively high (15mg/Kg) concentrations of safrole.

Conclusion

The classification of safrole as a Category 2 human carcinogen and the association of risk phrase R22-45-68 with the material seems disproportionate to the risks involved to humans from its traditional uses in spices, flavours, fragrances etc. Regulators appear to be forced by some unseen hand to deny the use of any traditional natural ingredients which have been shown to carry some health risks to susceptible animals at high doses, in an attempt to construct a clean, risk-free and largely synthetic-based world of their own. That is not the world that most of us wish to inhabit, and Cropwatch believes that many will ignore any restrictions which deny us the use of those familiar materials which we associate with our lives, our heritage & our traditions.

References:

Benedetti M.S., Malnoë A. & Broillet A.L. (1977) "Absorption, metabolism and excretion of safrole in the rat and man." Toxicology 7(1), 69-83.

Bisset N. (1994) “Sassafras lignum.” in Herbal Drugs and Phytopharmaceuticals. Stuttgart, Germany: CRC Press (1994) pp 455–56

Boberg E.W., Miller E.C., Miller J.A., Poland A. & Liem A. (1983) “Strong evidence from studies with brachymorphic mice and pentachlorophenol that 1′-sulfooxysafrole is the major ultimate electrophilic and carcinogenic metabolite of 1′-hydroxysafrole in mouse liver.” Cancer Res. 43, 5163–5173.

Bolton J.L., Acay N.M. & Vukomanovic V. (1994) “Evidence that 4-allyl-o-quinones spontaneously rearrange to their more electrophilic quinone methides: potential bioactivation mechanism for the hepatocarcinogen safrole.” Chem. Res. Toxicol. 7, 443–450.

Choong Y.-M. & Lin H.-J. (2001) “A Rapid and Simple Gas Chromatographic Method for Direct Determination of Safrole in Soft Drinks.” Journal of Food and Drug Analysis 9(1), 27-32.

Dietz B. & Bolton J.L. (2007) "Botanical dietary supplements gone bad." Chem Res Toxicol. 20(4), 586–590.

Daimon H., Sawada S., Asakura S. & Sagami F. (1998) "In vivo genotoxicity and DNA adduct levels in the liver of rats treated with safrole." Carcinogenesis. 19(1), 141-6.

Daimon H., Sawada S., Asakura S., & Sagami F. (1997-1998) "Inhibition of sulfotransferase affecting in vivo genotoxicity and DNA adducts induced by safrole in rat liver." Teratog Carcinog Mutagen. 17(6), 327-337.

Daimon H., Sawada S., Asakura S. & Sagami F. (1997) "Analysis of cytogenetic effects and DNA adduct formation induced by safrole in Chinese hamster lung cells." Teratog Carcinog Mutagen. 17(1), 7-18.

Duke J. (2002)

Gold et al.- see Carcinogenic Potency Project @ www.potency.berkeley.edu/. (‘through Levy D.D. (undated) below.

Gupta K.P., van Golen K.L., Putman K.L. & Randerath K. (1993) "Formation and persistence of safrole-DNA adducts over a 10,000-fold dose range in mouse liver." Carcinogenesis 14, 1517–1521.

IARC (1976). “Some Naturally Occurring Substances.” IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, Vol. 10, 231-244. Lyon, France: International Agency for Research on Cancer.

IARC (1987). IARC Monographs on the Evaluation of the Carcinogenic Risk of chemicals to Humans: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1-42, Supplement 7, 51, 65.

Jeng J.H., Wang Y.J., Chang W.H., Wu H.L., Li C.H., Uang B.J., Kang J.J., Lee J.J., Hahn L.J., Lin B.R. & Chang M.C. (2004) "Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells." Cell. Mol. Life Sci. 61, 83–96.

Jeurissen S.M.F. (2007) Bioactivation and genotoxicity of the herbal constituents safrole, estragole & methyleugenol. Thesis Wageningen University, The Netherlands (2007).

Levy D.D (undated) “Eugenol & the allylbenzenes: a case study on genotoxic risk.” – see http://www.gta-us.org/2008Presentations/Levy.pdf

Liu C.J., Chen C.L., Chang K.W., Chu C.H. & Liu T.Y. (2000) "Safrole in betel quid may be a risk factor for hepatocellular carcinoma: case report." CMAJ 162(3): 359–360.

Luo G. & Guenthner T.M. (1996). "Covalent binding to DNA in vitro of 2',3'-oxides derived from allylbenzene analogs.” Drug Metab. Dispos. 24, 1020–1027. [N.B. Erratum appears in Drug Metab Dispos 25(1), 131].

Lawrence B.M. (1990) “Progress in essential oils.” Perfumer & Flavorist 15, 63-69.

MAFF (1996) Food Surveillance Paper No. 48, Flavourings in Food, London, HMSO.

MAFF (1994) Food Surveillance Sheet No 30, June 1994 - Table . London HMSO.

Miller E.C., Miller J.A., Boberg E.W., Delclos K.B., Lai C.C., Fennell T.R., Wiseman R.W. & Liem A. (1985) “Sulfuric acid esters as ultimate electrophilic and carcinogenic metabolites of some alkenylbenzenes and aromatic amines in mouse liver.” Carcinog. Compr. Surv. 10, 93–107.

Patri G., Silano V. & Anton R. (2002) “Plants in Cosmetics.” Council of Europe Committee of Experts on Cosmetic Products, Council of Europe. 2002.

Randerath K., Putman K.L. & Randerath E. (1993) “Flavor constituents in cola drinks induce hepatic DNA adducts in adult and fetal mice.” Biochem. Biophys. Res. Commun. 192, 61–68.

Segelman A.B. (1976). JAMA 236, 477.

Stillwell, W. G. et al. (1974) “The metabolism of safrole and 2',3'-epoxysafrole in the rat and guinea pig.” Drug Metabolism & Deposition 2, 489-498.

Technorati Tags: safrole,chinese angelica,betel oil,camphor oil,cangerina oil,cinnamon oils,kuromoji oil,mace oil,mango ginger oil,nutmeg oils,pepper oil,sassafras oil,star anise oil,ylang ylang oil

Melissa Oil & IFRA Policy (cont’d): The Further Details

by Tony Burfield, Cropwatch, 6^th Sept 2009

For previous posts on this topic see here and here.

Preamble

Those of us who have worked in the aroma trade for most of their working lives, have, at times, been highly skeptical of the knowledge & abilities of those unelected officials who would impose baffling & seemingly nonsensical regulations and codes of practice upon the trade. Sometimes we felt that we were being regulated by those who had little in-depth knowledge or experience of the subject - a feeling which has never really gone away.

Perhaps safety-orientated organisations like IFRA would have gained more credibility from some of us old-timers if they had more openly owned up to their previous errors. Yes, we accept that with improvements in experimental design and better techniques, many of IFRA’s earlier (nineteen seventies’) findings on ingredient toxicology are now suspect, or have been superseded. Most importantly, the failure to use rigorously purified aroma chemicals for toxicology testing by researchers reporting to RIFM, and the use of complex botanical materials from non-expertly identified botanical sources, has thrown large sections of IFRA’s previous toxicological findings into doubt since impurities and adulterants have often been responsible for adverse effects rather than the pure ingredients. From a personal standpoint, when you have been drenched in perfume & essential oils on a daily basis for 30-odd years, as many of us at the coalface have, you may feel some intuition (rightly or wrongly) for what aroma materials might be posing any handling risks. This is why many of us laughed openly over IFRA’s Quenching Hypothesis (now discredited). It is why we are still cynical over the disproportionate IFRA classifications of many materials which are supposed to be sensitising, according to the corporate-toxicological methodology involved in the QRA approach. But many of these ingredients indicated as sensitisers have failed to produce any significant numbers of adverse reactions amongst the end-users of fragranced cosmetic & household products in which they occur.

Melissa Oil: Lesson Learned

The curious case of the previous banning of Melissa oil as a fragrance ingredient by IFRA, gave Cropwatch an opportunity to explore IFRA’s ingredient policies in detail (see previous Cropwatch reports). In so many instances, a veil of secrecy obscures the detailed experimental facts on which IFRA/REXPAN ingredient status decisions are made. Following requests by Cropwatch, Robertet Grasse, to their immense credit, were willing to share their toxicological findings on Melissa oil testing, referred to in the RIFM data-base but otherwise not available to the general public. Subsequently we can now clearly see (in our opinion) that there was no good reason to ban Melissa oil from perfumery use in the first place, and a case for its continued restriction is heavily based on Robertet’s evidence, which was not comprehensive across a range of dosages, but based on a strategy to reduce costs. This involved contriving experiments at doses which were likely to produce a positive safety outcome, rather than the prospect of funding a more extensive range of tests proving its skin safety at higher dosages. That’s OK - we can easily deal with this, because it represents the truth. It’s just that IFRA didn’t previously reveal these particular facts about the economic restraints which have materially affected the testing strategies, for this particular ingredient.

Where do we go from here? It is apparent that we need an independent body to openly ascertain the facts about ‘pure’ toxicological science – as against the corporate-funded version of toxicology which we are forced to follow. It is also apparent from the mail that Cropwatch receives that there are other expert opinions out there – why must these individuals be sidelined and denied places on expert committees? Above all, Cropwatch is concerned that the low standards set out in many IFRA commercial standards may be rubber stamped & adopted by the EU Commission, as of course has happened previously, and which may come to be an increasing trend.

Melissa Oil – the Further Details

With a few minor punctuation changes, the reply from Catherine Gadras is set out below (we had asked for the exact botanical identification of the Melissa spp distilled for essential oil (since IFRA had failed to properly define it), and for its’ geographic origin & compositional details. We had further asked the Robertet team for any views on the presented HRIPT & EC3 data. We also had an exchange of mails with Michel Meneuvrier of SAPAD who provided the oil for testing (see below) & who confirmed that the Melissa plants distilled for oil were produced organically from Diois region plants.

Catherine writes:

As I mentioned below Melissa EO used for testing is Melissa officinalis subsp. officinalis L cultivated in the South East of France in the region of Di (Drôme). This genuine essential oil has been provided to us by the SAPAD (Société Anonyme des Plantes Arômatiques du Diois).
The sample was taken from the crop 2008. 7 to 8 levels of fresh leaves plus the flower part are used for the distillation.
Please find below the range of the main constituents provided to us by SAPAD and the composition of the sample used in the most recent tests. (See attached file: Melissa-EO Composition.pdf).[This file consists of the tables included an the end of the post – Ed.]
The crop results from the distillation of 3 cuts: one at the end of May and the two others from the beginning of July and at the end of August/beginning of September. The producer finds that the citral content is maximum in the third cut (greater than 50%) and that citronellal is below 10%.
2) Comments regarding safety data (HRIPT and EC3)
The LLNA has been made to determine a level of concentration at which one begins to observe induction of sensitisation. In our case 4500µg/cm².
Considering the high cost of this EO (5 to 7 tons of fresh plants to
produce 1 Kg of essential oil) on one hand and the fact that we did not want to risk a positive reaction in the HRIPT, we have chosen this conservative 1470µg/cm². 1470µg/cm². This is more than adequate for perfumery use which is our business. It is quite possible that a higher safe limit for melissa EO exists but in my opinion it must be verified by testing my opinion it must be verified by testing.
PS: I take advantage of our e-mail exchanges to make some comments concerning the Cropwatch report on Melissa (page 3) that I found on internet :
I have 2 comments on this sentence below: :
"Under the draft proposals for IFRA’s 44th Amendment, melissa oil (which they describe as ‘genuine Melissa officinalis L.’) has been downgraded from an outright ban in fragrances, to a concentration restriction in the fragrance compound (as opposed to the finished cosmetic product). QRA data for melissa oil, which is categorised as a weak sensitiser, is presented by IFRA for the various established product categories, based on a No Expected Sensitization Induction Level (NESIL) of 1400µg/cm²."

1) Did you really mean "downgraded" ? My poor English would have expected "upgraded". (Cropwatch comments: downgraded from a negative position (a ban) but upgraded to more positive position (just a restriction) - it all depends on how you look at it!).

2) I confirm to you that the QRA limits are in finished consumer products and not in fragrance compounds.” (Cropwatch comments: on this latter point we stand corrected. Thank you Catherine!).

Addenda – Analysis Data received from Robertet.

Analysis of Melissa EO sample used in HRIPT test.

Component	% FID CW
Myrcène	0,16
Limonène	0,37
Cis Ocimène	0,12
Trans Ocimène	1,14
Para cymène	0,15
Methylheptenone 1	1,76
Octène 1 ol 3	0,4
Citronellal	1,3
Alpha copaene	0,34
Beta bourbonene	0,4
Linalool 1,38	1,38
Cis + Trans Isocitral	1,6
Beta Caryophyllene	14,2
Neral	23,8
Methyl geraniate	0,32
Germacrene	4,3
Geranial	33
Geranyl acetate	2,2
Delta Cadinene or delta Amorphene 7	0,7
Citronellol	0,2
Nerol	1,1
Isogeraniol (cis+trans)	0,24
Geraniol	1,7
Epoxydes de caryophyllene (cis+trans)	1,8
Germacradienol	0,3
Muurolol T	0,4
Thymol	2,1
carvacrol	0,25
Alpha Cadinol	0,6
Neric acid	0,1
Geranic acid	0,3
TOTAL 96,73

Information Stat from SAPAD

	Mini %	Maxi%	Moyenne %	Escart Type %
Methyl heptenone	1.05	3.36	1.8	0.7
Limonene	0.04	0.48	0.18	0.13
Citronellal	0.6	19	4.9	4.4
Neral +citronellol	6.4	28	18.7	5.4
Geranial + Geraniol	9	38.3	25.6	7.4
Caryophyllene beta	10.1	29.6	18.3	4.4

Technorati Tags: Melissa officinalis,Melissa,IFRA,Robertet,RIFM

Notes and News

Those involved in natural cosmetics and the manufacture of aromatherapy products  in the United States are not always aware of what’s percolating in regulatory circles across the pond.  There is a searchable database, COSING, established by the EU, which is extremely helpful to quickly find pertinent information.  These regs may or may not appear in our own rules here at home as the FDA continues to masticate on the globalization act of 2008.   Of the greatest interest, rules regarding the 26 fragrance allergens now required to be labeled on cosmetic packaging if in products above 10 ppm in leave-on products, or 100-ppm in wash-off products.  Perhaps 50% of these allergens are found naturally in limonene, citronellal and linalool . . . all which occur in essential oils.  In this directive, fragrance allergens are considered regardless if they come from essential oils or synthetic manufacture. 

We owe great thanks to Tony Burfield for his diligence over the past two years to provide information here on aromaconnection about EU directives, IFRA and other regulatory issues.

The volunteers at aromaconnection have all been very busy with other aspects of their lives for a bit of time, however, we hope to be back stronger than ever by the fall.      

Robertet Reveals its Evidence on Melissa Oil to Cropwatch

by Tony Burfield July 2009

You may remember that Cropwatch was quite puzzled by any need for IFRA’s new restrictive Standard for Melissa oil in IFRA’s 44^th Amendment, and had requested details of three unpublished toxicology reports from both RIFM & Robertet, Grasse, which were not available in the public domain, but which were cited by IFRA as containing evidence sufficient to restrict its use in perfumery. The back-story on this matter is available in the Cropwatch Files at http://www.cropwatch.org/Meliissa officinalis - Cropwatch article archive.pdf, but to briefly recap, although Melissa oil & extracts occupy an important place in aromatherapy and herbal medicine, Melissa oil is virtually unused in corporate perfumery. Nevertheless IFRA had previously seen fit to ban it as an ingredient on the basis of undisclosed evidence. There seemed to be no such body of evidence within the RIFM data-base to support such a ban, and it is a complete mystery to many of us how REXPAN could have come to such a conclusion. The ban has now been transformed into a concentration restriction under IFRA’s hyper-bureaucratic QRA system. In the interests of Freedom of Information, Cropwatch has compiled a comprehensive bibliography of the available literature on Melissa oil in the Cropwatch Files section of its website, to enable any interested parties amongst the general public at large to make their own minds up about the need for any restriction.

Although RIFM has ignored Cropwatch’s request for the withheld evidence on Melissa oil as noted above, Catherine Gadras of Robertet, Grasse very kindly responded with a summary of the test data, which is displayed at http://www.cropwatch.org/Melissa EO testing summery.pdf, and offered to answer any further points. Accordingly we asked Robertet (on 14^th June) to accurately define the botanical nomenclature of the Melissa species employed (was it, for example, the oil from Melissa officinalis L. subsp. officinalis?), the geographical origin of the Melissa herbage used to steam distill the essential oil, and the compositions of the oils employed in the research (since commercial Melissa oils vary widely – see Cropwatch’s Melissa oil bibliography). We also asked, in as many words, if the Robertet team would like venture any comments on the fact that there was a complete lack of adverse human reactions in the Robertet HRIPT studies, contrary to the numerical indications of possible sensitiser activity shown by the EC3 value? Without going into too many further details, this data would seem to offer further support as to the flawed ability of the LLNA test to accurately predict sensitiser potency for aromatic ingredients, and its questionable place of this animal-based test within the over-bureaucratic QRA system. But presumably, unless a notable such as Professor Axel Schnuch stands up and gives a paper on perfume ingredients with indicatory EC3 values which do not produce a significant number of adverse reactions per 10,000 dermatitis patients, no action will be taken by IFRA or by the `EU’s ‘expert’ committees to scrap this flawed QRA system (we make this comment since Schnuch’s evidence seems to have contributed to the pressure on the EU Cosmetics Commission to belatedly review the situation regarding notorious 26 Allergens debacle - see Cropwatch Files).

If we receive a further reply from Robertet regarding further details of the toxicological studies on Melissa oil, we will post it in the public interest. We should point out that in asking these questions, we did not mean to place Robertet in an awkward position (Robertet being a Direct Company Member of IFRA). However as Martin Watt noted when presented with the Robertet studies summary recently: “(the data presented)… is all typical in-house testing and certainly NOT suitable for ANY scientific evaluation purposes.” And further: “My key point is that RIFM data is only trade recommendations.  The EU committee is attempting to turn those 'recommendations' into EU law.  So far without success, but they keep trying. Only publicly discrediting that committee and the administrators in the European court will anything change.”

Cropwatch’s feeling is that the IFRA/RIFM/REXPAN conglomerate is struggling: better toxicological facilities & superior expertise in specialized subject areas are available outside the organisation, and this situation together with the fact that people are better informed on toxicological matters is stretching the credibility of many of IFRA’s policies and its decision-making generally. The perfume industry certainly needs a safety organisation to protect its interests – but maybe not this one, which is guilty of over-regulating the industry, and confuses the career interests of its composite toxicologists over and above its function to be a balanced safety policy-making unit for the trade.

Technorati Tags: Melissa officinalis,Melissa,IFRA,Robertet,Martin Watt,RIFM,REXPAN,IFRA 44th Amendment

IFRA’s Proposed 44th Amendment. More Grief.

Copyright © Tony Burfield, May 2009

Update on Melissa Oil

You may recall the recent Cropwatch posting to Aromaconnection on a proposed IFRA restriction for Melissa oil, and the non-availability of the relevant evidence in the public domain. Following separate Cropwatch requests to the holders of the privately-held information (Robertet & RIFM), Catherine Gadras, in charge of the regulatory and safety department of Robertet, Grasse, has mailed promising to forward a summary to Cropwatch by 15^th June 2009, in respect of the LLNA and HRIPTs  tests that have been conducted on behalf of Robertet, ‘in order to allow the use of this EO for perfumery use’. This is a welcome development. RIFM have not, as yet, either replied or acknowledged the request.

Further Points on IFRA’s Proposed 44^th Amendment

We are looking below at three further proposed IFRA Standards under the forthcoming 44th Amendment, which have recently been circulated to IFRA membership groups for comment, with a 3^rd June 2009 deadline.

Vanillin – Some Brief Notes

The first consideration is a proposed new IFRA Standard for vanillin. Readers will be aware that amongst flavour & fragrance ingredients, vanillin is possibly the most important aromatic aldehyde, with its easily recognisable & attractive powdery sweetness. It is available as a costly natural product via isolation from the vanilla pods of Vanilla planifolia G. Jacks, in which it occurs at up to 23,000 ppm, & via various biofermentation routes from natural starter materials (e.g. Rhodia have a microbiological biotranformation process using ferulic acid from rice bran). The production of vanilla itself was estimated at 2,000 tons in 2001 (Biolandes 2001), with 70% of the total production going to the US & Canada. Production rose to 3,600 tons in 2008 (Manceau 2009), but there are problems ahead, including pricing & compositional issues for vanilla from Uganda & Papua New Guinea, the effects of Madagascar’s political crisis, and from the damage caused by the fungi Fusarium oxysporum & Phytophthora spp. infecting Malagasy vanilla vines (see Gleason 2009; Manceau 2009). This is sufficiently serious that Dominiques Roques of Biolandes (through Gleason 2009) estimates a 1,200 ton/annum vanilla production loss from Phytophthora infection. Perfumery ingredients produced from Vanilla spp. (absolute, oleoresin, tincture, oil, CO₂ extract etc.) are too familiar to describe in detail here. Vanillin also occurs as a minor component of a number of essential oils (e.g. star anise, clove bud & asafetida oils), and in absolutes, and balsams (e.g. Peru balsam, benzoin Siam, benzoin Sumatra).

The production volume of the cheaper & more easily available synthetic vanillin (which has previously run at approx 1% or less of the price of natural vanillin) has been estimated at about 6,000 tons/annum, & the material has been historically prepared from feedstocks such as guaiacol, catechol, ortho-dinitrochlorobenzene & lignin; nowadays synthetic vanillin is mainly derived from guaiacol and glyoxylic acid. Opdyke (1977) previously found vanillin to be relatively non-toxic, non-irritant & non-sensitising. The OECD SIDS report on >99% pure vanillin (20.08.1996) concluded that in animal tests, vanillin was sensitising in 5 out of 10 studies, but was not sensitising in the only test conducted under GLP. Vanillin was also said to be non-sensitising at 2% in maximisation tests carried out on 25 human volunteers.

According to information seen by Cropwatch, the true situation may be even more complex, since in trials with human volunteers >99% pure vanillin ex lignin was found to be non-sensitising, whereas vanillin ex guaiacol. or via the former ortho-nitrochlorobenzene process, provoked sensitising reactions in some individuals. Vanillin prepared from certain natural sources may also be slightly sensitising [of the 110 separate Vanilla spp., only 3 are cultivated: V. planifolia G. Jacks (Bourbon or Indonesian vanilla), V. tahitensis Moore (Tahitian vanilla), and V. pompona Schneide (Guadeloupe vanilla; vanillons; W. Indian vanilla). Eighty percent of vanilla production occurs in Madagascar; other producing areas include/have included Uganda, Papua New Guinea, Comoros & Reunion (the latter producing vanilla “Bourbon”), Java, Tahiti, Martinique, India (production hit by Fusarium infection), Sri Lanka, Tanzania & the Seychelles].

Cropwatch believes that there is more to learn about the alleged weakly sensitising properties of vanillin, and the effects of minor impurities, just as was about coumarin, although this has still to be recognised by the legislators.

.

Vanillin – Uses in Perfumery

Vanilla occupies a important position in perfumery, having been widely employed in formulations, especially as a key ingredient in orientals, for more than a century. First use in Jicky (Guerlain1889) was followed by Narcisse Noir (Caron 1912), Shalimar (Guerlain 1925), Old Spice (Shulton 1937), Opium (Yves St. Laurent 1977) & Lagerfield (Lagerfield 1978), Vanillin has also featured in more recent orientals like Joop! Femme (Parfums Joop 1987). Vanillin is also employed in florientals, & in modern perfumes like JP Gaultier's le Male, & in the class of Vanilla fragrances themselves which were very popular in the mid ‘nineties e.g. Vanilla Fields Coty 1993). Today vanillin is also key material in sweet foody type perfume notes e.g. toffee, chocolate and berry notes, such as strawberry.

Vanillin under IFRA’s 44^th Amendment

Proposed Limitations for vanillin in the finished product under the QRA system fan out as follows:

Category 1 0.03 % (Lip products, toys, insect repellents)

Category 2 0.04 % (Deodorants/Antiperspirants)

Category 3 0.17 % (Hydroalcoholic Products for Shaved Skin, Eye Products, Men’s Facial Cream & Balms, Tampons)

Category 4 0.50 % (Hydroalcoholic Products for Unshaved Skin, Hair Styling Aids & Sprays, Body Creams)

Category 5 0.26 % (Women’s Facial Cream/Facial Make-up, Hand Cream, Facial Masks, Wipes/Refreshing Tissue for Hands, Face, Neck, Body)

Category 6 0.80 % (Mouthwash, Toothpaste)

Category 7 0.08 % (Intimate Wipes, Baby Wipes, Insect Repellent (intended to be applied to the skin)

Category 8 1.10 % (Make-up Remover, Hair Styling Aids Non-Spray, Nail Care)

Category 9 5.00 % (Shampoo, Rinse-Off Conditioners, Bar Soap, Feminine Hygiene Pads & Liners)

Category 10 2.50 % (Detergents, Hard Surface Cleaners, Diapers, Toilet Seat Wipes)

Category 11 “Should not exceed the usual concentration of the fragrance compound in the finished product”. (All Non-Skin or incidental skin contact products)

IFRA’s newly proposed restrictions under the 44^th Amendment for the extremely weak sensitiser, vanillin, seem to be largely based on three reports, two of which are internal RIFM reports (and one of which is only in draft form). These are not freely in the public domain. These are as follows:

Basketter D.A., Wright Z.M., Warbrick E.V., Dearman R.J., Kimber I., Ryan C.A., Gerberick, G.F., White I.R. (2001). “Human potency predictions for aldehydes using the local lymph node assay.” Contact Dermatitis, 45, 89-94.

RIFM (Research Institute for Fragrance Materials, Inc.), 1970. Maximization study with vanillin. RIFM report number 1760, October 7. (RIFM, Woodcliff Lake, NJ, USA).

RIFM (Research Institute for Fragrance Materials, Inc.), 2009. Human repeated insult patch test. DRAFT REPORT. (RIFM, Woodcliff Lake, NJ, USA).

It is impossible for fragrance companies to approve or make comment on the scientific robustness of the evidence for making these restrictions, if they cannot see all the evidence. It would seem important therefore IFRA/RIFM to make these studies available in the public domain, especially since the newly reported evidence flies in the face of previous conclusions about the sensitising potential of vanillin. It is slightly unclear, too, whether the newly proposed IFRA Standard just refers to deliberately added vanillin in fragrance compounds, or to the total vanillin content of the fragrance (i.e. including contributions from vanillin-containing natural materials).

As a final point, many have written in to Cropwatch pointing out that the toxicological investigation / restriction of components which are found in natural complex materials, is being pointedly pursued, whereas the toxicology of closely related & commercially available synthetic materials is being ignored. In this particular case, no mention is made of the any investigation of closely related synthetic, ethyl vanillin. Good to see people are thinking for themselves, but previous investigators [e.g. Patlewicz et al. (2001) & Basketter et al. (2001)] found ethyl vanillin to be non-sensitising, which may rather deflate the argument! Other investigations which show a similar lack of breadth in the selection of natural & synthetic ingredients to investigate, include the studies made by Hagvall et al. regarding possible mechanisms for dermal sensitisation by linalol & geraniol (see updated Cropwatch article at http://www.cropwatch.org/The Trouble with Oxidation of Essential Oils.pdf). We have also been treated by the academics concerned, via the trade press & websites dealing with health matters, to opinions about what these studies indicate for the users of cosmetics containing linalol- & geraniol-rich essential oils. Regarding the linalol studies, to our knowledge no investigation has been made of the widely-used & closely related synthetic, ethyl linalol, and many have concluded, rightly or wrongly (& bearing in mind their reported remarks in the press) that these researchers are riding on an anti-naturals ticket. Cropwatch considers a more likely explanation is that the academics concerned have a limited experience of the cosmetics trade & the available choices of commercial aromatic ingredients.

Estragole (methyl chavicol)

The draft document showing the IFRA proposal for the restriction / prohibition of estragole to 0.02% in fragrance compounds looks like an unfinished piece of work. The grounds cited for the restriction / prohibition, are those of alleged carcinogenicity, but, somewhat surprisingly, no supporting evidence or references are supplied in the circulated draft of the new Standard.

The restrictions, if applied to the total estragole content of a fragrance compound, including naturally-occurring estragole from natural ingredients and not just to added estragole, will severely impact on the use of those essential oils in which estragole naturally occurs in cosmetic products. These include star anise (to 6.4%), exotic basil (to 90%), fennel sweet (to 6.4%) and tarragon (to 82%), as well as more minor amounts in bitter fennel, cananga & ylang ylang oils & absolutes, and the oils from certain Pinus spp. The point was also made by Cropwatch at the SCS Symposium (Burfield 2009) that limitations on substances like safrole, methyl eugenol & estragole have already had significant effects on the fragrance styles entering the marketplace - traditional aromatic masculine fougères and rich spicy notes are very difficult to achieve at the so-called ‘safe’ levels for these materials. There is little prospect of substitution either – the contribution of estragole, for example, to the odour profile of naturals and finished fragrances, is virtually irreplaceable. So here we have another prospect of IFRA further restricting the art of the possible in the fragrance art with the progressive introduction of their restrictive Standards.

So what is the evidence? Animal experiments using high doses of estragole have led to its classification as a possible weak genotoxic hepatocarcinogen (SCF 2001). Other expert committees have come to different conclusions. The FEMA Expert Committee concluded that dietary exposure to estragole did not constitute a cancer risk, and ventured that a non-linear relationship exists between dose, profiles of metabolism, and covalent binding of estragole to protein and DNA (Smith et al. 2002). We in the aroma industry do not need to be caught in the crossfire of differing toxicological opinions anymore – rather we need firm evidence that this same situation (of zero cancer risk) does not similarly apply to bio-available estragole from the application of estragole-containing fragrances to human skin.

Benzaldehyde

Continuing the potential damage to the usage of natural aromatic products, IFRA are also introducing a new Standard limiting benzaldehyde concentration in fragrance compounds. Benzaldehyde is, of course, the major component in bitter almond oil, and is used to create almond and cherry notes in perfumes & flavours. Because of its pungency and odour character, it is also used in reodourants perfumes. Benzaldehyde is a minor component of many other natural products, including cinnamon leaf oil; cassia oil; cassie, narcissus & champaca absolutes; some cistus oils; clove oils & rosewood oil. Natural benzaldehyde is available from peach, cherry & plum stone processing, and via biofermentation routes e.g. starting from natural cinnamaldehyde ex cassia oil.

The grounds for the proposed restriction of benzaldehyde in perfume compounds by IFRA are based on the alleged weak sensitising properties of benzaldehyde, for which three references are quoted by IFRA:

Basketter, D.A., Wright, Z., Gilmour, N.J., Ryan, C.A., Gerberick, G.F., Robinson, M.K., Dearman, R.J., Kimber, I., 2002. “Prediction of human sensitization potency using local lymph node assay EC3 values.” The Toxicologist, 66(1-S), 240.

RIFM (Research Institute for Fragrance Materials, Inc.), 1973. Maximization study with benzaldehyde. RIFM report number 1802, October 11a. (RIFM, Woodcliff Lake, NJ, USA).

RIFM (Research Institute for Fragrance Materials, Inc.), 2009. Human repeated insult patch test. DRAFT REPORT. (RIFM, Woodcliff Lake, NJ, USA).

Again, the clincher for many of us in being able to judge the robustness of the scientific evidence necessitates the public availability of the draft RIFM report listed above.

Comments

In conclusion, these three IFRA proposals appear to be incompletely assembled and over-hastily produced. As we previously noted, until we know any further judgment from the EU legislators on the acceptability of the corporate-science styled QRA technique (following the SCCP’s severe criticisms in SCCP/1153/08), it would seem expedient to hold back on the implementation of this further set of IFRA Standards, if only to avoid unnecessary industry costs. Any communication on these matters from the authors of documents cited above, from RIFM or from the EU Cosmetics Commissioner, will be circulated by Cropwatch.

References

Basketter D.A., Wright Z.M., Warbrick E.V., Dearman R.J., Kimber I., Ryan C.A., Gerberick G.F. & White I.R. (2001) "Human potency predictions for aldehydes using the local lymph node assay." Contact Dermatitis 45(2), 89-94.

Biolandes (2001) – figures quoted in Biolandes Letter No 30 July 2001.

(Burfield 2009) – see http://www.cropwatch.org/Legislators & Natural Aromatics on PowerPoint.ppt

Gleason J. (ed.) (2009) “The state of vanilla: challenges & opportunities.” Perf & Flav. 34, 20-22.

Manceau M. (2009) “Thugs, Bugs & Vanilla.” Perf & Flav. 34, 24.

Patlewicz G., Basketter D.A., Smith C.K., Hotchkiss S.A.M. & Roberts D.W. (2001) "Skin-sensitization structure-activity relationships for aldehydes." Contact Dermatitis 44(6), 331-336.

Smith R.L., Adams T.B., Doull J., Feron D.J., Goodman J.I., Marnett L..J., Portoghese P.S., Waddell W.J. et al. (2002) “Safety assessment of alkyloxybenzene derivatives used as flavouring substances –methyl eugenol & estragole” – FCT 40,851-870.

Technorati Tags: IFRA,IFRA 44th Amendment,Melissa Oil,Vanillin,melissa officinalis,Vanilla planifolia,vanillin,vanillin uses in perfumery,ethyl vanillin,ethyl linalol,estragole,methyl chavicol,benzaldehyde,RIFM,SCCP,EU Cosmetics Commissioner

IFRA Reveals its Toxicological “Evidence” against Melissa Oil

by Tony Burfield May 2009

Pre-amble

It has always been something of a curiosity that IFRA has previously seen fit to prohibit melissa oil (lemon balm oil) which derives from Melissa officinalis L. ssp officinalis, as an ingredient of fragrances. The reasoning behind this, according to the published IFRA Standard for melissa oil, issued on 16-07-2008, was said to be:

1) presence of structural alerts as defined in the Human Health Criteria Document (Ford et al., 2000) and/or

2) adverse data on the material itself and/or

3) adverse data for a structurally related material based on toxicological concerns about its contained components from structural point of view.

Whilst melissa oil enjoys a considerable reputation in aromatherapy for its alleged beneficial properties, the usage volume of melissa oil in corporate perfumery nowadays has to be vanishingly small, perhaps running to no more than a few kilos per annum, since many perfumers consider the high cost of the ingredient is not justified by any contained unique notes, overall odour value, stability, or performance in product. In the days of early perfumery, the situation may have been different, for example Melissa officinalis was said to be an ingredient of the 17^th Century cordial Eau des Carmes. Melissa extracts on the other hand contain classes of compounds not found in the essential oil, which may have acetylcholinesterase inhibiting, anti-oxidant, anti-viral (e.g. exhibit action against herpes simplex viruses: Wolbling & Leonhardt 1994). and other useful properties Melissa leaf (under ‘lemon balm’) is official in the European Pharmacopoeia.

The Composition / Authenticity of Melissa Oil

There is a considerable amount of scientific literature on the composition & authenticity of melissa oil, and this brief review should only be taken as merely illustrative rather than fully comprehensive. Melissa oil rarely been commercially available in unadulterated form in the past, and was often a construct of citronella oil, litsea cubeba oil, lemon oil and various isolates & synthetics (Burfield 2008). Tisserand & Balacs (1995) had only identified possible toxicological concerns for melissa oil via its citral content, which they maintained was in the range 35-55%, concerns which presumably also apply to other high-citral containing oils such as lemongrass oil & litsea cubeba oil. Previously Schultze (1992) had investigated melissa flower oil, and found the corolla oil (yield 0.002%) to be different from the calyx oil, the latter resembling more the oil of the leaves. The main constituents of melissa leaf oil (Schultze 1989) were found to be citronellal (36.2%), germacrene D (13.5%), b-caryophyllene (10.9%), geranial (7.6%), and methyl citronellate (4.9%). Clery (1992) drew up some pointers to distinguish authentic melissa oil (including estimation of the geranial: citronellol ratio), in order to distinguish it from lemon-scented catnip oil from Nepeta cataria var. citriodora; this same topic was subsequently re-investigated by Klimek et al. (2000). In addition Clery indicates that the b-caryophyllene: geranial ratio is also important for the verification of authenticity, and the author cites a checklist of components normally found in genuine melissa oil. The position is further complicated by the ratio of top leaves to bottom leaves gathered, as the neral / geranial content is higher in the top leaves, whereas the sesquiterpenes are relatively higher in the bottom leaves – a topic further investigated by Mrlianova et al. (2001), who investigated essential oil composition at various harvest cut heights. Further, oil produced from the dried herb is claimed to be higher in neral & geranial, and lower in b-caryophyllene & caryophyllene oxide, than the fresh herb (Salaby et al. 1995). Melissa plants grown near the equator usually only grown in vegetative (non-flowering) form and so slight compositional differences may also arise from this consideration.

The evaluation of criteria for melissa oil authenticity was also discussed by Hener (1995) who used enantioselective gas chromatography, isotope ratio mass spectroscopy on-line coupled with capillary gas chromatography. Soresen (2000) reviewed the analysis, composition and pharmacological uses of Melissa officinalis extracts. Later, Lawrence (2008) reviewed a number of publications on melissa essential oils showing differences in composition due to the effect of different geographical sourcing, differing stages of maturity etc. Other melissa oils produced commercially include Melissa romana Mill.

Melissa Oil under IFRA’s 44^th Amendment

Under the draft proposals for IFRA’s 44^th Amendment, melissa oil (which they describe as ‘genuine Melissa officinalis L.’) has been downgraded from an outright ban in fragrances, to a concentration restriction in the fragrance compound (as opposed to the finished cosmetic product). QRA data for melissa oil, which is categorised as a weak sensitiser, is presented by IFRA for the various established product categories, based on a No Expected Sensitization Induction Level (NESIL) of 1400mg/cm². The problem for those of us who like to consider the robustness of the “evidence” supporting these proposed restrictions, is that it is alluded to in the form of 3 unpublished reports, not available in the public domain. These are as follows:

RIFM (Research Institute for Fragrance Materials, Inc.), 2001. Human repeated insult patch test. Unpublished study from Robertet, 21 February. Report number 36641. (RIFM, Woodcliff Lake, NJ, USA).

RIFM (Research Institute for Fragrance Materials, Inc.), 2008. Local Lymph Node Assay. Unpublished study from Robertet. (RIFM, Woodcliff Lake, NJ, USA).

RIFM (Research Institute for Fragrance Materials, Inc.), 2008. Human repeated insult patch test. Unpublished study from Robertet. (RIFM, Woodcliff Lake, NJ, USA).

Cropwatch has written to Robertet, Grasse, and to RIFM N.J., requesting that they make these reports publicly available, in the interests of transparency. We feel that this is particularly important in this case, in view of the devastating criticisms concerning the use of the QRA technique outlined in SCCP Opinion SCCP/1153/08, which directly related to the submitted RIFM / IFRA-generated data concerning citral as an alleged sensitiser (see feature on SCCP Opinion SCCP/1153/08 in Cropwatch Newsletter August 2008).

What to do about IFRA’s Discredited QRA Policy

In a new development, Matthias Vey of IFRA, speaking at the SCS Symposium (Grantham, May 2009) mentioned the fact that there are to be discussions on the QRA between the SCCP and IFRA. Previously Cropwatch had been told in a meeting at Brussels in 2007 with the European Cosmetics Commission, that communication between the SCCP and third parties (like Cropwatch) was not permitted, in order not the prejudice the SCCP, and to defend the committee from any criticism of partiality. We now seem to be in a situation where IFRA, a trade-funded business organisation, whose main activity is to sell scientific information on fragrances, is to have privileged access to a supposedly independent EU scientific committee to discuss an inherently contentious safety technique. Of course, IFRA has a lot to lose if the SCCP continue to discredit the QRA technique as the flawed piece of corporate-contrived science which it is, since IFRA have adopted this methodology as a tool to distinguish & restrict the use of any allegedly sensitising fragrance ingredients. Cropwatch has written to the Cosmetics Commissioner asking that this situation of unique access be either reversed, or that in the interest of fairness & to prevent possible bias, other interested parties should be granted similar opportunities to interact with the SCCP. Failing this, again in the interests of transparency, other parties should at least be granted observer status at important meetings which determine future cosmetics policy in this area.

References

Burfield T. (2008) – see http://www.cropwatch.org/adulterationupdate08.pdf

Clery R.A. (1992) An investigation of the variability of essential oil production in plants. Ph.D. Thesis, Univ. Reading, UK.

Hener U., Faulhaber S., Kreis P. & Mosandl A. “On the authenticity evaluation of balm oil (Melissa officinalis L.)”. Pharmazie (1995) 50(1), 60-62.

Klimek B., Majda T., Gora J. & Patoa J. (2000) “Investigations of the essential oil from lemon catnip (Nepeta cataria L. var. citriodora) in comparison to the oil from lemon balm (Melissa officinalis L.) Herba Pol. 46, 226-234.

Lawrence B.M. (2008) “Progress in Essential Oils. Melissa or Lemon Balm Oil.” Perf & Flav. 33 (*Sept 2008), 66-70.

Mrlianova M., Tekel’ova M., Felklova M., Renohl V. & Toth J. (2001) “The influence of the harvest cut height on the quality of the herbal drugs Melissa folium & Melissa herba.” Planta Med. 68, 178-180.

Salaby et al. (1995) “Oil of Melissa officinalis L., as affected by storage & herb drying” J. Essen. Oil Res. 7,: 667-9.

Schultze W.. Zanglein A.., Klose R. & Kubeczka, K.H. (1989) “Constituents of the essential oil from Melissa officinalis.” Planta Med. 57, 89-90.

Schultze W., Zanglein W., Hose S., Kubeczka K.H., Czygan F.C. (1992) “Volatiles in Flowers of Balm (Melissa officinalis L.)” in R. Hartley & T. Renolds (eds) Advances in Labiatae Science pp 357-366, Royal Botanic Gardens, Kew.

Sorensen J.M. (2000) "Melissa officinalis." Int. J. Aromatherapy 10(1-2), 7-15

Tisserand R. & Balacs T. (1995) Essential Oil Safety. Churchill-Livingstone 1995.

Wolbling R.H. & Leonhardt K. (1994) “Local therapy of herpes simplex with dried extract from Melissa officinalis” Phytomedicine 1. 25-31.

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