the aromaconnection blog

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.

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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.

Technorati Tags: melissa oil,melissa officinalis,IFRA

Cropwatch at the SCS Symposium, Grantham UK, 2009

Tony Burfield gave a talk entitled “Legislators & Natural Aromatics: a Modern Day Vendetta” at the Symposium on Cosmetic Controversies –Seeing the Whole Picture organised by the Society of Cosmetic Scientists, May 17-19th 2009. Power Point and pdf versions of the above presentation can be viewed in the newly reorganised Cropwatch Files section of the Cropwatch website. Matthias Vey of IFRA spoke immediately after Cropwatch, his talk being entitled “How Safe are Fragrance Raw Materials? The IFRA Principles for Safety Assessment.” In the interests of balance, we hope it eventually becomes possible to run both talks side by side, and for both parties to answer the other’s criticisms.

Looking to the future, Cropwatch has plans to become a funded operation later this year. Although we continue to expand our available data on natural products on the Cropwatch website, and to attract new Cropwatch Newsletter subscribers, and we continue to regularly receive pledges of support from many quarters, we feel that there is a limit to what can be practically achieved without funding. Our intention therefore is to run a series of courses in order to raise the necessary finance, which is to be spent on research into some of the contentious areas of aroma ingredient toxicity, which Cropwatch has previously identified. We hope to be able to announce the subjects and venues for the courses in due course.

Tony Burfield
Cropwatch.

Technorati Tags: Cropwatch,Natural aromatics,aromatics regulation,perfumery regulation,IFRA

Notes and News

• March 20  Botany Photo of the Day: Mentha ×piperita is an electron micrograph of mint that shows the essential oil droplets and glands on the surface of the leaf.
• Perfumer&Flavorist has a short note about “fair trade” sourcing of benzoin (Styrax tonkinensis) by the Swiss firm Givaudan, who have partnered with Agroforex from Spain and local villages in Laos to promote sustainable production and diversification.
• P&F also reports that Earthoil India has received “Fair for Life” accreditation for its Indian mint growing operation. From the Earthoil media center, they have also received certification for their African grower group at the foothills of Mt. Kenya.

Technorati Tags: mint,mentha x piperita,benzoin,fair trade,fair trade essential oils

Frankincense Oil may be a treatment for bladder cancer

According to a study published this week in BMC Complementary and Alternative Medicine 2009, 9:6, “Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity” scientists at the University of Oklahoma Medical Center have found in vitro evidence that frankincense oil (probably its constituent boswellic acid) can kill bladder cancer cells without affecting non-cancerous cells. In order to determine that frankincense was the effective oil, they compared it to sandalwood, fir, palo santo and hemlock oils which did not differentiate between the types of cells. The study used a commercial frankincense oil that was not specifically controlled for origin and constituency, and the authors suggest that future studies should be more rigorous in determining these details. [See our previous post on frankincense.]

The study references numerous other studies that have found that frankincense has potential in treating cancerous cells.

The abstract can be accessed at http://www.biomedcentral.com/1472-6882/9/6/abstract and a PDF of the full article is at http://www.biomedcentral.com/content/pdf/1472-6882-9-6.pdf

Technorati Tags: frankincense,frankincense oil,bladder cancer,boswellia carteri,boswellic acid,frankincense essential oil

Notes and News

• According to several Turkish newspapers are reporting that an Explosion at perfume shop injures 16 in Eski_ehir (in the central Anatolian part of Turkey. An investigation is underway, but apparently there was no gas connection to the shop, so it is possible it had something to do with perfume making.
• Cosmeticsdesign has a feature “Cosmetics Compact” that has an audio news component.  This week they are featuring news about essential oils and their ability to turn into allergens upon contact with the skin. For more information on that topic, see Tony Burfield’s blog from earlier this month, in which he questions these findings and points out that there is conflicting research.
• ScienceBooksChemistry reviews The Merck Index: An Encyclopedia of Chemicals, Drugs and Biologicals, which contains information about safety and toxicity and lots of other things, of interest to us are biologicals and natural products; plants and traditional medicines; nutraceuticals and cosmeceuticals; agriculturals, pesticides and herbicides; Organic chemicals used in research; and Food additives and supplements. Over 2500 pages in the book, and now includes a CD-ROM with additional information and a searchable database.
• The Daily Green is reporting that Colony Collapse Disorder is showing up again in East coast bee hives. While you’re reading the article, scroll down to the bottom of the screen and read some of the (alarming to me) related articles. If this news doesn’t concern you, then remember that many aromatic plants are pollinated by bees, not to mention food plants.

Technorati Tags: perfume explosion,essential oil oxidation,Merck Index,colony collapse disorder

The Trouble With Theories About The Oxidation of Essential Oils

by Tony Burfield Feb 2009.

Judging by the response from Cropwatch supporters, many of you may have already read about a doctoral thesis and remarks made by Lina Hagvall, distributed via the cosmetics trade press. Many professionals have found the reported remarks condescending, as we are well aware and may have a wider understanding of the context of oxidized aroma materials than the source of the remarks. But I digress. The thesis in question is entitled “Formation of skin sensitizers from fragrance terpenes via oxidative activation routes: Chemical analysis, structure elucidation”, and Katie Bird (Bird 2009) recently covered the story for Cosmetics Design Europe, although, as with any news knocking natural products, the article is being very widely circulated on websites dealing with health interest and other matters. Many of us have found the Bird-penned article makes for confusing reading: for example what is ‘geraniol oil’? A better recourse is maybe to download the thesis itself from the University of Gothenburg website at http://gupea.ub.gu.se/dspace/handle/2077/18951. You will then be able to gather that the thesis is primarily concerned with the consideration of substances without contact allergenic properties, but which can be activated either via autoxidation in contact with air, or via cutaneous metabolism, to reactive products which can cause contact allergy. Primarily the study looks a five published articles for which the author has had a major involvement, studying the oxidation of geraniol, geranial (a conformational isomer of citral), linalool, linalyl acetate & lavender oil. For convenience these articles are referenced below (Hagvall et al. 2007; Hagvall et al. undated; Hagvall et al. 2008; Skold et al. 2008; Hagvall et al. 2008a).

If I were one of Hagvall’s invigilators, I would have insisted on a re-write of a number of parts of the thesis, where the science as presented is dubious, incomplete or, most importantly, does not present an accurate overview of the topic. Some knowledge of industrial practices would have aided its general acceptability as well, and a collection of these points will constitute a future article from this author.

Overall this author is not saying that the elucidation of underlying mechanisms whereby oxidized essential oils, which may be the cause of type IV allergy and acute contact dermatitis, is not important. But an overview to enable to put this work in perspective is importantly missing. Further, the mention of Axel Schnuch’s work (Schnuch et al. 2007) is selective, and a major omission to include the toxicological reviews of Hostynek & Maibach’s on geraniol & linalool (Hostynek & Maibach 2007a; Hostynek & Maibach) is almost unforgivable, however inconvenient their conclusions to Hagvall’s work. The reader is thus left to form his/her own independent opinion on the relevance of the study, especially against a background of an increasing number of published studies on the anti-oxidative properties of essential oils, the declining concentrations & use of essential oils in fragrances generally, the use of cold-storage & nitrogen-blanketing (amongst other measures) to prevent the oxidative deterioration of stored essential oil and natural isolate ingredients, and the addition of anti-oxidants, UV-filters and stabilizers to finished fragrances & cosmetics to extend shelf-life One is also tempted to mention that a major contributor to the cost of the studies was RIFM, a primary instigator to the culture of toxicological imperialism which has overtaken the regulation of cosmetics/fragrances in the West.

How does this thesis change anything? The lack of evidence of a clear cause-effect relationship between geraniol and linalool and cases of allergic contact dermatitis has been previously emphasized by Hostynek & Maibach (2004 & 2008), and Cropwatch would guess from its’ own experience that adverse end-user effects would tend to support the same conclusion for lavender oil. Hostynek & Maibach (2008) also comment on the relative stability of linalool, its low oxidation rate kinetics and speculate negatively about how readily linalool would oxidize in fragrances & cosmetics, as well as low consumer exposure levels to the ingredients. Great store seems to have been put on the Hagvall thesis by IFRA/RIFM juggernaut, but considering the importance of the sensitiser issue to the perfumery trade, and its impact on the use of natural ingredients in perfumery, the sponsoring of just one researcher to look (mainly) at the oxidation of geraniol & lavender oil seems an exceptionally disproportionate response to the problem. Unless of course you believe that RIFM sees the future of perfumery as entirely synthetic.

Cropwatch is trying to work towards the sponsorship of toxicological research which emphasises a risk/benefit approach towards the elucidation of the safety of natural products - otherwise we will all drown in a sea of over-cautious toxicological negativity, which, it is becoming clear, has little relevance in terms of safety risks presented to the general public from natural-product containing products.

References.

Bird K. (2009) “Essential oils can become allergens on contact with air and skin, says researcher.” Cosmetics-Design Europe 5^th Feb 2009. Link

Hagvall L. (2009) “Formation of skin sensitizers from fragrance terpenes via oxidative activation routes: Chemical analysis, structure elucidation.” PhD Thesis University of Gothenberg. Link

Hagvall L., Bäcktorp C., Svensson S., Nyman G., Börje A. & Karlberg A-T. (2007) “Fragrance Compound Geraniol Forms Contact Allergens on Air Exposure. Identification and Quantification of Oxidation Products and Effect on Skin Sensitization.” Chem. Res.Toxicol. 20, 807-814. Link to HTML Version

Hagvall L., Börje A. & Karlberg A-T. (date unknown) “Autoxidation of Geranial.” (Unpublished?) Manuscript.

Hagvall L., Baron J. M., Börje A., Weidolf L., Merk H. & Karlberg A-T (2008) “Cytochrome P450 mediated activation of the fragrance compound geraniol forms potent contact allergens.” Toxicol. Appl. Pharmacol. 233, 308-313. Link to Abstract

Hagvall L., Sköld M., Bråred-Christensson J., Börje A. & Karlberg, A.T. (2008a) “Lavender Oil Lacks Natural Protection Against Autoxidation, Forming Strong Contact Allergens on Air Exposure.” Contact Dermatitis 59, 143-150. Link to Abstract

Hostynek J.J. & Maibach H.I. (2004) “Is there evidence that geraniol causes allergic contact dermatitis?” Exogenous Dermatology 3(6), 318-331. Link to Abstract

Hostynek J.J. & Maibach H.I. (2008) “Allergic contact dermatitis to linalool.” Perf. & Flav. 33 (May 2008), 52-56. Link to Excerpt

Schnuch A., Uter W., Geier J, Lessmann H. & Frosch PJ. (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. Link to html version

Sköld M., Hagvall L. & Karlberg A-T (2008).”Autoxidation of linalyl acetate, the main component of lavender oil, creates potent contact allergens.” Contact Dermatitis 58, 9-14. Link to Abstract

Technorati Tags: oxidation of essential oils,geraniol,geranial,linalool,linalyl acetate,lavender oil,fragrance sensitization,essential oil oxidation

Aromatics in Print

A review of some of the recent print magazines to come across my desk.  Links are supplied when articles are free online; otherwise you’ll have to visit your local library or subscribe.

• The January 2009 issue of Perfumer&Flavorist reports on the IFRA workshop on Allergy Prevalence in Fragrance held in November 2008 in Brussels; Reports on the Centifolia 2008 Conference featuring an article on “The Three Pillars of Smart Sustainability in F&F” that discusses how we can increase the usage of natural products while maintaining the natural environment; an article by Brian Lawrence “A preliminary Report on the World Production of Some Selected Essential Oils and Countries” (for example, did you know that 67% of orange oil, the #1 oil, comes from Brazil—or that Hungary is the largest producer of Blue Chamomile Oil?); and Brian Lawrence’s monthly column “Progress in Essential Oils” covers Orange Oil. The print magazine also provides links to online articles, particularly “FMA Ponders Green Fragrances”.
• The December 2008 issue of GCI (Global Cosmetic Industry) contains an article “What Do Ethical and Sustainable Mean to Today’s Beauty Consumer?” that raises some of the issues and discusses how some companies have dealt with the issues, concluding that “those companies seen to behave in an ethical and transparent manner are likely to win over today’s skeptical consumers.”
• The September 2008 issue of DAYSPA magazine discusses how organic applies to the Spa world in “You Say You’re Organic?”, something that seems to be open to interpretation in the Spa industry. [see previous note].
• The December 2008 issue of Economic Botany contains a paper “Traditional Tar Production from Cedrus libani A. Rich on the Taurus Mountains in Southern Turkey” (abstract) that describes how katran, a tar that has medicinal properties, from chips of old stumps that undergo a kind of distillation process involving burning them in a closed space. The katran is about half Monoterpenoids and Sesquiterpenoids, the remainder comprising hydrocarbons such as heptane. Not surprisingly, the chemical composition is similar to that of cedar essential oils.Traditional uses for katran include a number of medicinal uses for humans and animals, and as an insect repellant. Unfortunately the authors used “volatile oils” and not “essential oils” as a keyword, so the article may not be easily found by an online search.

Technorati Tags: sustainabiliity,essential oils,spa industry,essential oil production,katran,Cedrus libani

Cropwatch Newsletter Jan 2009 Published

The most recent Cropwatch Newsletter Jan 2009 [pdf] has been sent to subscribers and posted on the Cropwatch website. There is also an html format post elsewhere on the web, and several of the articles in it were previously posted on this blog, so we won’t do more than summarize it.

The Newsletter starts out with an Editorial on the theme 2008: A Bad Year for Natural Aromatic Ingredients.  A Good Year for Industry Consultants and Ingredient Clerks, in which Tony discusses the REACH Process, Corporate Influence over IFRA and its affect on the use of Natural Products, and the effects of increasing market demand for natural ingredients on the sustainability of the natural environment.

The articles included in the Newsletter are:

1. The REACH Pre-registration Exercise – an Autopsy
2. Sandalwood – A Critical View of Developments
3. IFRA Gives Up Supporting Two More Natural Aromatics:
Opoponax & Styrax Next for the Chop
4. Frankincense – A Brief Catch-Up
5. The Art of Natural Perfumery: Under Threat from Natural &
Organic Cosmetic Certifying Organisations?
6. The Oakmoss & Treemoss Saga – Slight Return
7. GM Fragrance Anyone? – Hopefully No Takers
8. IFRA Workshop - Allergy Prevalence in Fragrance, November
4, 2008, Brussels, Belgium
9. More on Ylang-ylang oil

Articles 2, 3 and 4 are updated and slightly expanded from articles previously published on this blog. Click on the number for links to the posts here: 2 3 4 however you may want to read the PDF version to get the latest information.

Article 5 on the Art of Natural Perfumery is a detailed analysis and response to the various attempts by various organizations to develop Organic and Natural Standards to control the ingredients used. This topic has been previously discussed on this blog; you can find the articles filed under the category Standards. Tony takes several of the standards to task and closes his article with:

We could review proposals from other organisations, but we think you get the idea ….. both natural & organic cosmetics are a long way from living up to the promise of their descriptions. The lack of common sense is also worrying – for example, banning added synthetics such as UV filters (one thing that Cropwatch would allow) which as well as increasing the shelf-life of the product, arguably
help protect against the risk of solar/UV-induced skin cancer. This ban, taken with other considerations, means that evolving versions of natural & organic cosmetics may be in danger of becoming considerably less safe than conventional cosmetics.

Regarding natural fragrances, it can be guessed that many of us who have been involved in the teaching, promotion & development of the art of Natural Perfumery over the past several years may be getting a bit hot under the collar when whole classes of raw natural aromatic ingredients are suddenly declared “not natural” by the self-proclaimed officials of certifying organisations, who don’t appear have experience across all the areas they are proposing to regulate. The exclusion of concretes, absolutes & resinoids from an inventory of natural aromatics for fragrances intended for natural cosmetics may well pander to the more chemophobic amongst cosmetics customers. But the banning of petrochemical solvents cannot be justified on health grounds relating to supposedly harmful amounts of solvent residues that remain in these materials – since there is no health risk. We should also mention that there is a move to allow solvent extraction in the form of allowing CO2 extracts and bio-ethanol. The protagonists of these proposals do not make clear how they are going to determine whether the CO2 used in such processes is natural (i.e. produced by fermentation of natural materials etc.), or how they will propose to police the matter. Cropwatch’s guess is that (a) they haven’t thought about it and (b) they can’t guarantee it (thanks to Daniel Joulain for bringing this to our attention). The
proposed allowable use of bio-ethanol is welcome, but does not substitute for the elimination of other solvents.

We can clearly see that attempts by these certifying organisations to redefine natural cosmetics, and natural cosmetic/aromatic ingredients clearly bow to the business interests of the major international cosmetic companies and their customers, who are the potential cash-cows that these organisations are trying to milk. The multinational’s interests in the natural personal care sector has been plain enough for all to see – L’Oréal bought out The Body Shop, Estée Lauder did the same with Aveda & Clarins took over Kibio, just to mention three. That doesn’t mean to say that those of us working with natural products now have to dance to a tune played by the big corporates, or the organisations that suck up to them. We feel that many of the above-cited proposals & guidelines will be rejected by those purists who have been involved with natural perfumery to its
present point. You probably do not need Cropwatch to tell you that many experienced older perfumers have been found surplus to requirements lately by some of the Aroma Giants, probably because they are too expensive compared with younger perfumers. Many of these more experienced professionals are now working independently, making a living by creating natural perfumes. It is
unlikely, we feel, that this group will accept many of the definitions currently proposed by these Natural & Organic Cosmetic Certifying Organisations, and hopefully this group will become a growing influence in this area, for better values, independent of big industry’s requirements.

The Oakmoss/Treemoss article updates an article in this blog several months ago and announces that a detailed review of the lichens is planned for publication in Flavour and Fragrance Journal by mid-February 2009.

The GM Fragrance article discusses the progress? made in the floral products industry to increase the fragrance of flowers through GMO manipulation and the possibility that this will be a back door entry into the aromatics industry in spite of public opposition (especially in the EU) to Genetic Modification. The article contains several references and additional reading.

Brief comments on the IFRA workshop on Allergy Prevalence in Fragrance suggest a possible out for IFRA on the current over-regulation of the European cosmetics industry with a report that

sensitization to fragrance ingredients has decreased considerably over the years, and for some weak allergens, the rate of incidence is now so low that several thousands of subjects now need to be tested
to obtain one genuinely positive result.

The Ylang Ylang article is an update and correction to comments made in the previous Cropwatch Newsletter (Sept 2008) having to do with coniferyl benzoate in (or not in) ylang-ylang oil. Tony goes on to clarify the current status of the Ylang market.

All in all, a useful and interesting issue. Recommended reading for a variety of topics and interests.

Technorati Tags: REACH,Sandalwood,IFRA,Frankincense,Natural Perfumery,Oakmoss,Treemoss,GM Fragrance,Ylang-ylang

Frankincense – A Brief Catch-Up

Copyright ã Tony Burfield. Jan 2009.

The year 2008 saw the publication of a number of papers on the analysis & therapeutic properties of Frankincense gum, extracts & distillates, and it is only in recent years perhaps, that we are gaining further insight into the true nature & therapeutic potential of these various exudations & preparations. The whitish-yellow or yellow-orange tears or lumps of Frankincense gum (syn. Olibanum) (syn. Incense) are obtained by tapping the trees of a number of Boswellia spp., and the gum & derivatives are valuable exported commodities for the Horn of Africa region (Djibouti, Ethiopia, Eritrea, Somalia & the island of Socotra (Yemen)), but also for Sudan and other African regions. Frankincense gum is used to prepare incense, and extracts & distillates have been widely used as fragrance ingredients. Indian, Arabian & African Boswellia spp. have a number of uses in local ethnic medicine, which is starting to translate into uses in evidence-based conventional medicine (see for example, the major feature on Frankincense & derivatives in Phytomedicine, June 2008).

For a working definition, we can say that Frankincense is the dried exudation obtained from the schizogenous gum-oleoresin pockets in the bark of various Boswellia spp - the Boswellia group itself being placed within the Burseraceae family. The Boswellia group constitutes some 25 species of shrubs or small trees found in the dry tropical areas of N.E. Africa, S. Arabia and India (including N.E. Tanzania and Madagascar) growing at a height of 1000 to 1800 m.:

 

Boswellia Species.	Eritrea	Ethiopia	Somalia	Sudan	India	Kenya	Oman	Nigeria
Boswellia bhau-dajiana Birdw.*			X
B. dalzielii Hutch.								X
B. frereana Birdw.			X
B. microphylla Chiov.		X
B. neglecta S. Morre		X	X			X
B. ogadensis Vollesen		X
B. papyrifera (Del.) Hochst	X	X		X
B. pirottae Chiov.		X
B. rivae Engl.		X	X
B. sacra Flück **		X	X
B. serrata Roxb.					X		X

Table 1. Distribution of some Boswellia spp.
*some now say syn. B. sacra Flück ** syn. B. carteri Birdw.

Frankincense – Uses

Frankincense has been very highly valued for thousands of years, dating to pre- Roman times, and has many uses & applications. It is the Horn of Africa’s highest volume export, and apart from uses in incense/perfumery, the gum oleoresin & preparations thereof are also used in a number of medicinal systems, for flavourings (‘maidi’ type of frankincense preferred) & for skin cosmetic applications for toner, emollient & anti-wrinkle uses.

Survival Pressure on Boswellia spp.

Several Boswellia spp. are listed in the IUCN Red List of Threatened Species 2008, including several individual spp. from the island of Socotra, off Yemen. However, some Frankincense- yielding species of commercial importance would also appear to be under threat e.g. Boswellia papyrifera in Eritrea, Ethiopia & Sudan (see Cropwatch’s Updated List of Threatened Aromatic Plants Used in the Aroma & Cosmetic Industries v1.09 Dec 2008). The results of the analysis of the essential oils from three threatened Boswellia species from Socotra have recently been published (Awadh Ali et al. 2008).

Frankincense - Anti-inflammatory Effects

Given the use of Indian Frankincense (B. serrata) gum-oleoresin in treating inflammatory disease in Ayurvedic medicine, a number of researchers have investigated the anti-inflammatory & anti-arthritic effects of the Boswellia resins. Frankincense contains α- and β-boswellic acids from 3α-hydroxy-olean-12-en-24-oic acid and 3α-hydroxy-urs-12-en-24-oic acid respectively, amongst others. Boswellic acid & pentacyclic triterpene acids are marketed as anti-inflammatory & anti-arthritic drugs in India (Handa 1992). Examples of commercialised products containing boswellic acids include ‘H15’ and ‘Sallaki’. Another, ‘Boswellin’ (a patented product of Sabinsa Corporation) is described as the standardized ethanol extract of Boswellia serrata gum resin, containing 60% to 65% boswellic acids.

The mechanism of the anti-inflammatory action may occur via the inhibition of 5-lipoxygenase (and hence leukotriene biosynthesis: Ammon et al. 1993; Ammon 1996). This action taken together with inhibition of human leukocyte elastase (Safayhi et al. 1997) may constitute the basis of the anti-inflammatory effect, since both of these enzymes play key roles in inflammatory & hypersensitivity-based diseases. The most active inhibitor of 5-lipoxygenase seems to be acetyl-11-keto-beta-boswellic acid, which is also cyctotoxic to meningioma cultures (Park et al. 2000).

The use of Boswellia preparations to treat another inflammatory disease, ulcerative colitis, may also owe its beneficial action to 5-lipoxygenase inhibition (Gupta et al. 1997).

Anti-carcinogenic Effects.

Leading on from the above, extracts of B. serrata & boswellic acids & their derivatives have been investigated by a number of researchers for their (chemopreventive) anti-carcinogenic/anti-tumorigenic effects via their cytotoxic & apoptosis effects in various in vitro cell lines. In particular acetyl-11-keto-beta-boswellic acid shows strong cyto-toxic activity against meningioma cell-lines and is the strongest 5-lipoxygenase inhibitor yet tested amongst triterpenoids (Hostanska et al. 2002). See Cropwatch’s Frankincense Bibliography v1.02 Jan 2009 for further details.

Use in Treating Respiratory Disease.

Gupta et al. (1997) investigated the use of Boswellia serrata gum resin in patients with bronchial asthma in 23 males & 17 females with a history of the disease, in a double-blind, placebo-controlled, 6-week clinical study, 70% of the patients showed an improvement (against a 27% improvement in the control group).

Incense: the Purifying Smoke.

The smoke of incense is traditionally used in Arabia & NE Africa for its deodorizing and purifying effects. Basar (2005) showed that the pyrolysates of Boswellia carterii & B. serrata resins showed anti-bacterial inhibition for contained certain substances e.g. 24-norursa-3,12-diene, incensole acetate & cembrene A, in the case of B. carterii. The author concluded that the results could support the successful use of certain Boswellia resins as a disinfectants in traditional ceremonies.

Analysis.

The literature is beset with analytical investigations of non-botanically verified frankincense samples, often obtained from local markets. A few papers have been published more recently where proper botanical identification has been established. One such paper is that of Hamm et al. (2005) who analysed the mono-, sesqui- & di-terpene contents of 6 olibanum samples of botanically certified origin. For example the characteristic chemical compounds of Boswellia papyrifera were stated as the diterpenic biomarkers incensole and its oxide and acetate derivatives, n-octanol and n-octyl acetate.

References.

Ammon H, et al. (1993) “Mechanism of antiinflammatory actions of curcumine and boswellic acids.” J. Ethnopharmacol 38(2-3), 113-19.

Ammon H. (1996) “Salai guggal Boswellia serrata : from a herbal medicine to a non-redox inhibitor of leukotriene biosynthesis.” Eur J Med Res 1(8), 369-70.

Awadh Ali N.A., Wurster M., Arnold N., Teichert A., Schmidt J., Lindequist U. & Wessjohann L. (2008) "Chemical Composition and Biological Activities of Essential Oils from the Oleogum Resins of Three Endemic Socotraen Boswellia Species." Rec. Nat. Prod. 2(1), 6-12

Basar S. (2005) Phytochemical investigations on Boswellia species: Comparative studies on the essential oils, pyrolysates and boswellic acids of Boswellia carterii Birdw., Boswellia serrata Roxb., Boswellia frereana Birdw., Boswellia neglecta S. Moore and Boswellia rivae Engl. PhD Thesis, Universität Hamburg 2005.

Gupta I., Gupta V., Parihar A., Gupta S., Ludtke R., Safayhi H. & Ammon H. P. (1998). “Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study.” Eur. J. Med. Res. 3, 511-514.

Hamm S., Bleton J., Connan J. & Tchapla A.(2005) "A chemical investigation by headspace SPME and GC-MS of volatile and semi-volatile terpenes in various olibanum samples." Phytochemistry. 66(12), 1499-514.

Handa S.S. (1992) Fitoterapia 63(10), 3.

Hostanska K., Daum G. & Saller R. (2002) "Cytostatic and apoptosis inducing activity of boswellic acid towards malignant cells in vitro.” Anticancer Research 22, 2853-62.

Gupta I., Parihar A., Malhotra P., Singh G. B., Ludtke R., Safayhi H. & Ammon H.P (1997) “. Effects of Boswellia serrata gum resin in patients with ulcerative colitis.” Eur J Med Res . 2(1), 37-43.

Park Y.S., Lee J.H., Bondar J., Harwalakr J.A., Safayhi H. & Golubic M. (2000) “Cytotoxic action of acetyl-11-keto-β-boswellic Acid (AKBA) on meningioma cells.” Planta Med. 68, 397-401.

Safayhi H., Rall B., Sailer E-R. & Ammon H.P.T. (1997) "Inhibition by boswellic acids of human leukocyte elastase." Pharmacology 281(1), 460-463.

Technorati Tags: Frankincense,boswellia,frankincense extracts,frankincense distillates,frankincense gum