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

Cosmetics Database reliability questioned

 

1000fragrances expresses some concerns about the reliability of the Skin Deep cosmetics Database. This reiterates some concerns I had when I was looking at the database a few months ago. For those of you unfamiliar with the database, it allows companies to enter their product ingredients and then evaluates the safety of the product, assigning a hazard score of 0-10. Consumers concerned about the safety of products can look them up and obtain an assessment of their relative safety.  It sounds like a good idea, but it appears to have a faulty evaluation mechanism. Unless the user is careful in evaluating the data, and understands the limitations of the evaluation, it may be useless. They do state what they call a “data gap” that assesses what data is unknown. In the case cited by 1000fragrances the data gap for the “good” product is 81%, which suggests to me that they are admitting they don’t really know whether it is safe or not. The “bad” product has a data gap of 64%.

The difference seems to be that the ingredients in the “good” product are listed as essential oils, while the ingredients in the “bad” product are listed by their constituent chemical names. And the “bad” product contains a number of ingredients that are indeed synthetic or hazardous in some way, in addition to the essential oil constituent chemicals that are listed. So indeed the “bad” product may be bad. 1000fragrances makes the point that the “good” product is also potentially hazardous, even though it gets a “good” score.

One reason the “bad” product scores badly is because one of the ingredients is “fragrance”, which is allowable as an ingredient by the FDA, but is considered as “bad” by the Environmental Working Group because it could contain anything.

Given that the Compact for Safe Cosmetics and EWG seem to be prepared to jettison the small businesses who have been the innovators in the Safe Cosmetics industry by blindly supporting the regulation of the industry through the  FDA Globalization Act of 2008/9, perhaps it is time to reconsider whether participation in the Cosmetics Database is a good idea. It certainly products some strange results.

Technorati Tags: Cosmetics Database,FDA Globalization Act of 2008

Brussels makes a conciliatory move over the ‘26 Allergens’ debacle

by Tony Burfield March 2009

Cropwatch has been campaigning for a number of years to change the situation regarding the 26 alleged allergens (16 of which occur in natural products) which carry a labeling obligation where the concentration of any one identified fragrance substances in the final cosmetic product is 0.01% or above for products rinsed off the skin, or 0.001% or above in leave-on products. This requirement was incorporated into Council Directive 2003/15/EC, whereby these materials were moved into Annex III of the Cosmetics Directive. The basis for the inclusion of these substances as allergens has never been explained by the SCCP (Storrs 2007).

Independent papers/peer-reviews/comments (e.g. Schnuch (2004),  Vocansen (2006 & 2007), and several by Hostynek & Maibach) have indicated that there is no robust clinical or experimental evidence to support many of these 26 ingredients as allergens. Up to now there has seemed to be no mechanism to independently review the SCCP’s Opinion, or undo Directive 2003/15/EC, although Schnuch (2008) had openly asked the EU to rethink their policy.

In a new move, a request for an updated scientific opinion on the labeling of 26 fragrance substances has been made by Brussels to the SCCP, apparently being described as a spin-off from the public consultation (Nov 2006) on the Commission proposal of regulation of some fragrance substances.

"Scientific information of general and specific nature has been submitted to DG ENTR in order to ask the SCCP for a revision of the 26 fragrances with respect to further restrictions and possible even delisting.“

“At that time there were not sufficient scientific data to allow for determination of dose response relationships and/or thresholds for these allergens.”

…And that’s presumably the nearest we will ever come to an apology from Brussels, for the imposition of over-precautionary and unnecessary legislature, which cost the industry millions of Euros in reformulation and labeling costs at the time, and presumably will again, with any new situation. The passage of the original legislation depressed the production of some essential oils worldwide for at least two years afterwards, reflecting their reduced usage in cosmetics. This arises from the fact that the large majority of essential oils, absolutes & resinoids contain several of the 26 named allergens, and cosmetic manufacturers wished to avoid excessive product labeling. The decline in the overall usage of essential oils in fragrances from this cause is still felt today.

What is needed now is an independent impact assessment, sponsored by DG-Environment, to find out the damage caused to industry, and especially to SME’s, over the whole 26 allergens legislatory debacle. Cropwatch identifies one of the problems as the chemophobic attitudes of some European governments, who have been led by the nose by career toxicologists, who have exaggerated the ingredient risks posed by allergens. This pressured situation has pushed the EU Cosmetics Commissioner into over-hasty legislation over this matter. What has been missing in this situation is a realistic overview and the application of common sense, and we can only hope that lessons have been learned In Brussels, before the aroma industry, or parts of it, are totally bankrupted.

References

Schnuch A. (2008) – remarks attributed to Schnuch by the trade media during the IFRA workshop on Allergy Prevalence in Fragrance Nov. 2008 e.g. by Montague-Jones in Cosmetics-Design Europe 18.11.2008

Storrs F.J. (2007) “Allergen of the year: fragrance.” Dermatitis 18(1),3-7 [linked version is a Medscape reprint]

Technorati Tags: fragrance,26 allergens,allergens,SCCP,cosmetics ingredients

Sassafras oil distillers help destroy Cambodian forest

Copyright © Tony Burfield March 2009.

Illicit manufacturers of MDA, MDEA & MDMA (ecstasy) can utilise safrole from safrole-rich essential oils such as sassafras oil and “brown” camphor oil as starter materials (precursors). Therefore safrole & sassafras oils are designated as controlled substances in many countries, and safrole is listed as a Table 1 precursor under the United Nations Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances. Since sassafras trees (Sassafras albidum (Nutt.) Nees) grow wild in the Eastern parts of the US, the Drugs Enforcement Agency has made safrole a List 1 substance under the under the Chemical Diversion and Trafficking Act, and it is unlawful to trade safrole & safrole-rich substances for illicit drug-manufacturing purposes. There are legitimate uses for safrole however - these include the manufacture of the aroma chemical heliotropin (‘cherry pie’) and the knock-down insecticide piperonyl butoxide. Interestingly, there is a tradition of drinking sassafras tea, of using sassafras as in ingredient in sarsaparilla drinks, and making root beer from the inner bark of young sassafras tree roots. Dried ground sassafras leaves, in the form of aromatic filè powder, is also used in cooking, being stirred into traditional Southern dishes just before serving. The FDA made sassafras a prohibited ingredient for food & beverages in 1976, since it is a weak experimental animal carcinogen (rats, mice) - Daimon et al. (1998). It has to be said that there is some resistance amongst many US citizens in accepting that safrole is actually the heptacarcinogen it is made out to be. The latest EFFA Code of Practice for example lists safrole both as carcinogen category 2, and as a mutagen category 3m. It is fair to day that the amount of evidence for safrole’s role in human carcinogenicity is scanty, even at this point in time, although there is very limited evidence of oral cancers from long-term safrole exposure from betel-leaf and areca-nut chewing practices (Chen et al. 1999). So the traditions of sassafras tea drinking (often made from the sassafras tree’s twigs & leaves) still persists in places, such as is still found within N. American Indian communities in Eastern parts of Canada. In the Eastern US, many citizens regard the right to use sassafras as part of their cultural inheritance, although any commercial root beer listing sassafras as an ingredient is now made with safrole-free sassafras extract.

N. American sassafras essential oil has a sweet-spicy peppery odour, with an underlying woodiness; the dry-out on a perfumers strip being invariably spicy and woody. Safrole has a cleaner, candy-like odour and its previous uses in perfumery included deployment in re-odourant formulae & soaps. In flavourings safrole was used as an ingredient to flavour medicinal products and confectionery. 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% for both skin contact & non-skin contact fragrances. This causes a potential problem for utilization of many safrole-containing fragrance ingredients, such as nutmeg butter; safrole-free versions of various aromatic nutmeg ingredients are commercially available, but often lack the spicy-sweetness and body of the authentic versions.

In South America, the safrole-rich chemotype of Brazilian sassafras tree Ocotea pretiosa (Nees) Mez. has been over-exploited as a safrole-source (there is also a methyl eugenol chemotype). As early as 1966 Mors and Rizzini (Mors & Rizzine 1966) noted that O. pretosia was becoming scarce in Santa Catarina due to uncontrolled exploitation and the natural slow growth of the tree. So Brazil went from being a major supplier of sassafras oil in the ‘sixties, to being a minor supplier in the nineties. Vietnam took over the role of being the major supplier, felling the tree Cinnamomum parthenoxylon (Jack) Meisn. to distill the roots to produce hundreds of tons of sassafras oil Vietnamese annually. Cropwatch (2007) declared the tree as now being critically endangered in Northern & Central Vietnam. Other geographic sources of safrole include Yunnan, China, where C. parthenoxylon, Sassafras tzumu & fractions of C. camphora are utilized for domestic piperonyl butoxide & heliotropin manufacture.

In S.W. Cambodia, sassafras trees (‘Mreah Prew Phnom’) Cinnamomum parthenoxylon are especially found amongst the 2 million ha. of forest within the Cardamom mountains. On-going investigations of illegal oil-producing activity were started in 2004 by the Flora & Fauna International Group. In a recent move, made together with help from the Ministry of the Environment, illegal distilleries were discovered within the Phnom Samkos Wildlife Sanctuary, run by Vietnamese syndicates, producing sassafras oil from the shredded roots & trunk of the Mreah Prew Phnom trees

Rangers from the Phnom Sankos Wildlife Sanctuary prepare to dismantle illicit sassafras oil still. Credit D. Bradfield – FFI. (used with permission.)

Subsequent action by the Royal Cambodian Armed forces dismantled 2 factories and led to 2 arrests. Tim Wood, FFI Field Co-ordinator at the Phnom Samkos Sanctuary is quoted as expressing grave concern that the harvesting of these trees is destroying the fragile eco-system habitats within the sanctuary. The FFI press release describes the pollution of streams used for cooling water for the distillation, and mentions the abstraction of fuel wood to drive the distillation process. Local peoples fear that this rate of abstraction could push the forest & Mreah Prew Phnom trees to the brink of extinction within 5 years. As a mark of their success, the 25^th Feb 2009 FFI press release also mentions the fact that in June 2008, 33 tons of illicitly produced sassafras oil were destroyed, and the 2009 FFI raids reported above have to be put in context – since previously in 2006 there were some 75 operating stills in the Western Cardamom Mountains. Now however, the FFI are apparently facing funding problems and need economic help to continue their work.

References.

Chen C.-L., Chi C.-W., Chang K.-W., & Liu T.-Y. (1999) "Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history." Carcinogenesis 20(12), 2331 - 2334

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, 141-146.

Flora & Fauna International 25^th Feb 2009. “‘Ecstasy oil’ distilleries raided in Cambodia’s Cardamom Mountains.” Media Release, Phnom Penh, Cambridge.

IRIN –UN Office for Humanitarian Affairs “Cambodia: Ecstasy tabs are destroying the forest wilderness” – see http://www.irinnews.org/Report.aspx?ReportId=79340

Mors & Rizzini (1966) Useful Plants of Brazil pub. Holden & Day, 1966.

Segelman A.B., et al (1976). "Sassafras and herb tea: potential health hazards." JAMA 236(5),477.

Technorati Tags: sassafras essential oil,brown camphor essential oil,ecstasy,safrole

Bio-Piracy, Bio-Prospecting, Local Treatments & Ayurvedic Medicine

Copyright © Tony Burfield Feb 2009

Cropwatch has previously featured articles concerned with the fact that intellectual property relating to traditional treatments & medicines, and other exploitable properties of useful plants, has been looted or otherwise misappropriated. These acts have been carried out by multinational companies and in some instances by unscrupulous individuals or teams within universities. The pharmaceutical industry, of course, has a long history of bio-piracy - you have only to think of well-known long-standing drugs such as reserpine & vincristine where no recompense was paid to the communities where the drug was found. Some examples of misappropriation for nine Indian medicinal plants were given in a discussion-only document by UNCTAD India Team (2005), which was reproduced in Cropwatch’s Updated list of threatened aromatic plants used in the aroma & cosmetic industries v.10 Jan 2009.
 

Plant name	Patents Revealed (use similar to Traditional Knowledge).
Acorus calamus L. (Vacha)	3 granted, 7 applied
Adhatoda vasica Nees (Vaska),	1 granted
Andrographis pinacualta Nees (Kalmegh)	3 granted
Commiphora mukul Engl. (Guggul)	11 granted
Curcuma longa L. (Haldi)	20 granted
Phyllanthus amarus L.	4 granted
Rauvolfia serpentina Benth. (Sarpagandha)	19 granted
Swertia chirata Buch. – Ham. Ex Wall (Chirata).	None directly mentioned, but 3 applications need study.
Terrminila chebula Retz (Harar)	3 granted
Withania somnifera Dunal (Aswaganha)	1 granted, 1 applied

Table 1. Medicinal plants with patent claims possibly similar to Indian Traditional Knowledge (adapted from UNCTAD 2005 discussion document).

Quoting from the Cropwatch article: “The authors of this document (UNCTAD) point out, that for most USA patents relating to native Indian plants, the inventors are often Indian people of Indian origin, patenting uses of plants already used for the same purpose in Ayurvedic medicine. This surely must raise questions on whether these particular patenting authorities are “fit for purpose” by ‘mis-granting’ patents based on traditional knowledge, & in so-doing, failing to establish whether acts of misappropriation have occurred. A spokesperson for the US Govt. defended the performance of the US patenting authorities on this issue in 2001, stated: “The fault lies not with the patent system, however, but with the inaccessibility of the knowledge involved beyond the indigenous community” (Anon 2001). This feeble excuse for not spotting bio-piracy when it stares US officials in the face is simply not an acceptable position for a competent authority to maintain, but it certainly illustrates the need for recruitment of the appropriate expertise in this area.”

In a new departure, the Indian Government has effectively licensed 200,000 local treatments as “public property” which is intended to limit their use as a brand. This move was taken after Delhi scientists identified 5,000 bio-prospecting patents taken out by companies outside India. Dr Vinod Kumar Gupta, who heads the Traditional Knowledge Digital Library, was reported in the Guardian newspaper (Ramesh 2009) as saying more than 2,000 of these treatments belong to the seven Indian systems of medicine, and he wonders why so many millions of dollars are being spent by multi-nationals, when so many lobbies deny they work at all. Gupta’s remarks on these doubters brought a particular smile to the face of the author, as Cropwatch is currently gathering evidence of media & academic put-downs of those Complementary Alternative Medicines (CAM’s) which utilise aromatic plant treatments. This comes in a week when in an Education Guardian article, Lipsett (2009) discussed whether Alternative Medicine should be taught as a scientific subject at all, and mentions the cyber-bullying from anti-CAM lobbyists and their influential blogs, determined to shut down CAM courses at UK universities such as Salford, Uclan, Westminster, Middlesex, Thames Valley, West of England etc., and their attempts to totally discredit the practice of homeopathy.

Returning to the Ramesh-penned article, Gupta further mentions the granting of 285 patents in Brussels, which involve the properties of traditional Indian medicinal plants, and he would like these patents lifted. It will be very interesting to see the outcome, given the activities of the estimated 16,000 corporate lobbyists with very large cheque books, known to lurk in Brussels. Readers may remember however that Indian officials have previously been to court to successfully nullify patents taken out on the neem tree (which took them ten years), and on turmeric derivatives (which only took one).

You don’t have to look hard to find evidence of Ayurveda as the current buzz-word in cosmetics trade magazines. For example, an article on “Ayurvedic Beauty – here’s how to formulate beauty products based on the ancient Indian discipline” by Shyam Gupta of Bioderm Research (Gupta 2009) takes us through the principles of the Ayurvedic beliefs and describes topical treatments, Ayurvedic anti-aging ingredients, Ayurvedic skin-whitening ingredients, Ayurvedic arthritis, muscle & joint-pain relief ingredients & treatments, and a list of Ayurvedic herbs for further development together with their potential for ‘inside treatments’, as cosmeceutical agents, and for ‘outside treatments’. I am not a lawyer, I just believe in a fair world and treating people properly. I therefore have serious doubts about the operational ethics, & ultimately the legality of marketing certain products from companies such as Bioderm and Sabinsa (the latter company previously featured in Cropwatch articles). If the Indian Government start using their large financial resources to defend traditional plant uses and to stop their unlicensed exploitation by foreign companies, we could see a big shake-down in the cosmetics sector.

References

Anon (2001): US General Declaration to the First Meeting of the WIPO Committee 1st May 2001, through Balasubramaniam K. (2003) “Intellectual Property Rights & Herbal Medicine” Sri Lanka Association for the Advancement of Science Annual Scientific Sessions, December 2003. Theme Seminar “Herbal Medicines for the People” Sri Lanka Foundation Institute 10th December 2003.

Gupta S. (2008) “Ayurvedic beauty” Beauty Vol 3 (Fall 2008), 36-42.

Lipsett A. (2009) “The opposite of science.” Education Guardian 24.02.09 p8

Ramesh R. (2009) “India acts to stop foreign drug companies seeking patents on traditional remedies.” Guardian 23.02.09 p22.

Technorati Tags: ayurveda,ayurvedic,biopiracy,patents on traditional remedies

NSF's 'made with organic' standard becomes an American National Standard

Cosmeticsdesign.com (as well as lots of other sites) report that NSF's 'made with organic' standard becomes an American National Standard. This is the organic standard that was being promoted by Dr. Bronner’s Soaps that we blogged about last year. The “made with organic” bar is set fairly low, with only 70% of the ingredients required to be organic.  Products covered by the standard include rinse-off and leave-on personal care and cosmetic products, as well as oral care and personal hygiene products. You can read the original press release from NSF at their site.

The 58 page standard (NSF/ANSI 305-2009) was published February 10 by NSF, but unfortunately costs $100.00 USD for a printed or PDF version. The Table of Contents is available in PDF format for free. The current TOC appears to essentially be the same as that in a draft from early 2008 that I have a copy of (R6), but differences in the actual content are unknown. It would appear that anyone interested in claiming compliance with the standard will have to spring for the $100 for a copy.  However, if the certification process is anything like that planned for the “Natural” standards that are being proposed or adopted ($2500 per product on one of them) it seems that the standard will be well beyond affordability for small and handmade product manufacturers who have pioneered the use of Organic products.

There will be a logo for use by those complying with the standard:

  

One little tidbit from the Draft Standard:

7.1 The term "organic" shall only be used on labels and in labeling of raw or processed agricultural products, including ingredients, that have been produced and handled in accordance with the requirements of this Standard. The term "organic" shall not be used in a product name unless the product meets USDA-NOP criteria or criteria defined in this Standard.

Presumably this clause applies only to products claimed to meet the standard, but since this is now an ANSI standard should we worry that there might be an attempt to extend this to use by others such as essential oil vendors? 

Technorati Tags: organic standards,cosmetic standards,organic cosmetics,made with organic

The Senate affects Aromatics Stimulus

I took a look at the list of items cut from the Stimulus package by the Senate compromise team. Several items that will be cut may affect aromatics in the US. These include:

• $100 million cut from Farm Service Agency Modernization
• $50 million cut from Cooperative State Resources, Education, or Extension
• $65 million for watershed rehabilitation

What wasn’t indicated on the cut list whether there would be any funds remaining in these categories. What is clear that these cuts could potentially affect farming and farm services that might support aromatic crops. On the other hand, the proportion which might have trickled down to help aromatic crop farmers is probably small.

Final passage of the stimulus package in the Senate probably won’t come until Tuesday. There will then have to be a Conference Committee with the House to reconcile the differences between the House and Senate bills. It’s possible that some of these items might be put back in.

If you have any feelings one way or the other on this bill, you should contact your Senators or Congressperson.

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