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Fragrance Industry Update from Denmark


This was sent by an environmental health advocate from Denmark, December 30, 2003:


Subject: Limonenes from Shenet Aroma, Sweden - allergy testing with 'fresh'
or older limonene.....- some abstracts & fragrance chemicals from EU's list


Limonen har kvalat in i parfymhistorien på ett dubiöst sätt.
Det var med limonen man löste mysteriet med parfymer som passerade vartenda
allergitest men sedan ändå rapporterades ge massor av allergiska
reaktioner. Orsaken var att tester gjordes på fabriksfräscha produkter,
medan användarnas parfymer redan börjat oxidera, d.v.s. reagera med syret i
luften. Se vidare nedan under Hudreaktioner.

Limonenes have passed the allergy tests but the consumers reacted to them
with allergy.  The reason was that the tests were made with fresh limonenes
(brand new products).  The products used by the consumers had started to
oxidize, i.e. reacted with the oxygen in the air.

Limonen oxiderar snabbt i ljus och luft
Limonenes oxidize quickly in the light and air.

2002 kunde svenska forskare förklara åtminstone delvis varför allergitester
så ofta kommer fram till att hudvårdsprodukter inte kan irritera, fast folk
uppenbarligen lider av dem: Man testar med pinfärska produkter, medan folk
använder gamla. Svenska Arbetslivsinstitutet tänker nu föreslå berörda
myndigheter inom EU att oxiderat limonen ska ingå i standardtest för
doftämnesallergi, och svenska forskare med anknytning till institutet
deltar i EU-finansierade studier för att hitta nya allergener i doftämnen.
(Actually in industrial use it was found out that oxidized products caused

In 2002 the Swedish researchers were able to explain (at least partly) why
the allergy tests did not give positive reaction even if the person reacted
with allergy to limonenes.  The reason is that the tests are made with
fresh limonenes, but the persons use older ones.
The Swedish Institute for Occupational Health is going to suggest to the EU
that instead of testing with fresh limonenes, the 'perfume' allergy tests
should be made with oxidized limonenes.
Swedish researchers with connections to the Swedish Institute for
Occup.Health are participating in studies financed by the EU to find new
allergens among fragrance chemicals.


1: Contact Dermatitis 1997 Apr;36(4):201-6
Related Articles, Books, LinkOut
Contact allergy to oxidized d-limonene among dermatitis patients.
Karlberg AT, Dooms-Goossens A


1: Am J Clin Dermatol. 2003;4(11):789-98.  Related Articles, Links 

Fragrance contact allergy : a clinical review.

Johansen J.

Department of Dermatology, The National Allergy Research Centre, Gentofte
Hospital, University of Copenhagen, Copenhagen, Denmark.

Most people in modern society are exposed daily to fragrance ingredients
from one or more sources. Fragrance ingredients are also one of the most
frequent causes of contact allergic reactions. The diagnosis is made by
patch testing with a mixture of fragrance ingredients, the fragrance mix.
This gives a positive patch-test reaction in about 10% of tested patients
with eczema, and the most recent estimates show that 1.7-4.1% of the
general population are sensitized to ingredients of the fragrance mix.
Fragrance allergy occurs predominantly in women with facial or hand eczema.
These women typically have a history of rash to a fine fragrance or scented
deodorants. Chemical analysis has revealed that well known allergens from
the fragrance mix are present in 15-100% of cosmetic products, including
deodorants and fine fragrances, and most often in combinations of three to
four allergens in the same products. This means that it is difficult to
avoid exposure, as products labelled as 'fragrance free' have also been
shown to contain fragrance ingredients, either because of the use of
fragrance ingredients as preservatives or masking perfumes, or the use of
botanicals.About 2500 different fragrance ingredients are currently used in
the composition of perfumes and at least 100 of these are known contact
allergens. Therefore, it is advisable to supplement standard patch testing
with the patient's own stay-on cosmetic products, as well as the fragrance
chemical hydroxyisohexyl-3-cyclohexane carboxaldehyde, which on its own
gives responses in 1-3% of tested patients. The focus in recent years on
the ingredients of the fragrance mix will probably result in the fragrance
industry changing the composition of perfumes, and thus make the current
diagnostic test less useful. New diagnostic tests are under development to
identify contact allergy to new allergens, reflecting the continuous
developments and trends in exposure.

PMID: 14572300 [PubMed - in process]



1: Toxicol Lett. 2003 Nov 30;145(2):189-96.  Links

Increased airway responsiveness of a common fragrance component, 3-carene,
after skin sensitisation-a study in isolated guinea pig lungs.

Lastbom L, Boman A, Johnsson S, Camner P, Ryrfeldt A.

Division of Inhalation Toxicology, Institute of Environmental Medicine,
Karolinska Institutet, Box 210, S-171 77, Stockholm, Sweden

Lungs from skin-sensitised and non-sensitised guinea pigs were exposed via
the airways to 3-carene (1900mg/m(3)) and perfused with buffer containing
either autologous plasma or lymphocytes. The experiments were performed in
order to investigate the importance of blood components for the increased
lung responsiveness seen in skin-sensitised animals. A reduction in lung
function was noted in all lungs during 3-carene exposure. There was no
difference in the 3-carene response between lungs from skin-sensitised
animals versus lungs from non-sensitised animals when the perfusion buffer
contained lymphocytes. However, when plasma diluted with buffer was used as
perfusion medium, there was a significant enhancement in the response in
lungs from sensitised versus lungs from non-sensitised animals. This
implies that skin sensitisation increases lung responses to inhaled
3-carene and those components in plasma, and not the lymphocyte fraction,
contributes to the observed increased lung responsiveness.

PMID: 14581172 [PubMed - in process]



European Respiratory Society
congress press releases - tuesday, september 17, 2002


Avoiding fragrance-exposure is impossible. People are constantly exposed at
home, at work and in the environment. This is a great problem for those who
are hypersensitive to fragrances, but also for those who are chemically
sensitive and get breathing problems from inhaling these substances without
knowing why.

The aim of this study was to investigate the effects on the lungs and the
skin sensitisation potential of a commonly used fragrance component,
3-carene. (The pine smelling component in turpentine).


1: Contact Dermatitis 2002 May;46(5):267-72 Related Articles, Links 

Studies on the autoxidation and sensitizing capacity of the fragrance
chemical linalool, identifying a linalool hydroperoxide.

Skold M, Borje A, Matura M, Karlberg AT.

Occupational Dermatology, National Institute for Working Life, Stockholm,

Fragrances are among the most common causes of allergic contact dermatitis.
The two monoterpenes linalool and d-limonene are the most frequently
incorporated fragrance chemicals in scented products. Previous studies on
d-limonene show that this monoterpene oxidizes on air exposure
(autoxidation) and that allergenic oxidation products are formed. Due to
structural similarities, linalool might also form allergenic oxidation
products on air exposure. The aim of the present study was to study the
autoxidation of linalool and to investigate the sensitizing potential of
linalool before and after air exposure. Linalool was oxidized for 10 weeks
and gas chromatographic analyses showed that the content of linalool
decreased to about 80%. The chromatograms revealed the formation of other
compounds during oxidation. One of the major oxidation products was
isolated and identified as 7-hydroperoxy-3,7-dimethyl-octa-1,5-diene-3-ol.
This substance is, to the best of our knowledge, described for the first
time. In sensitization studies in guinea pigs, linalool of high purity gave
no reactions, while linalool that had been oxidized for 10 weeks sensitized
the animals. It is concluded that autoxidation of linalool is essential for
its sensitizing potential.

PMID: 12084079 [PubMed - indexed for MEDLINE]


1: Contact Dermatitis 2002 May;46(5):295-7

Lyral has been included in the patch test standard series in Germany.

Geier J, Brasch J, Schnuch A, Lessmann H, Pirker C, Frosch PJ; For the
Information Network of Departments of Dermatology (IVDK)and the German
Contact Dermatitis Research Group (DKG).

Information Network of Departments of Dermatology (IVDK), Georg August
University, Germany. jgeier@med.uni-goettingen.de

Lyral 5% pet. was tested in 3245 consecutive patch test patients in 20
departments of dermatology in order (i) to check the diagnostic quality
of this patch test preparation, (ii) to examine concomitant reactions to
Lyral and fragrance mix (FM), and (iii) to assess the frequency of
contact allergy to Lyral in an unselected patch test population of
German dermatological clinics. 62 patients reacted to Lyral, i.e. 1.9%.
One third of the positive reactions were + + and + + +. The reaction
index was 0.27. Thus, the test preparation can be regarded a good
diagnostic tool. Lyral and fragrance mix (FM) were tested in parallel in
3185 patients. Of these, 300 (9.4%) reacted to FM, and 59 (1.9%) to
Lyral. In 40 patients, positive reactions to both occurred, which is
13.3% of those reacting to FM, and 67.8% of those reacting to Lyral. So
the concordance of positive test reactions to Lyral and FM was only
slight. Based on these results, the German Contact Dermatitis Research
Group (DKG) decided to add Lyral 5% pet. to the standard series.

PMID: 12084084 [PubMed - in process]



1: Contact Dermatitis 2002 Aug;47(2):78-85 Related Articles, Links 
Further important sensitizers in patients sensitive to fragrances*

Frosch PJ, Johansen JD, Menne T, Pirker C, Rastogi SC, Andersen KE, Bruze
M, Goossens A, Lepoittevin JP, White IR.

Departments of Dermatology, Klinikum Dortmund gGmbH and University of
Witten/Herdecke, Dortmund, Germany, Gentofte Hospital, University of
Copenhagen, Department of Environmental Chemistry, National Environmental,
Research Institute, Roskilde, Department of Dermatology, Odense University
Hospital, Denmark, Department of Occupational and Environmental
Dermatology, University Hospital, Malmo, Sweden, Katholieke Universiteit
Leuven, Belgium, Laboratoire de Dermatochimie, Universite Louis Pasteur,
Strasbourg, France, St.John's Institute of Dermatology, St Thomas'
Hospital, London, UK.

The aim of this study was to determine the frequency of responses to
selected fragrance materials in consecutive patients patch tested in 6
dermatological centres in Europe. 1855 patients were evaluated with the 8%
fragrance mix (FM) and 14 other frequently used well-defined fragrance
chemicals (series I). Each patient was classified regarding a history of
adverse reactions to fragrances: certain, probable, questionable, none.
Reactions to FM occurred in 11.3% of the subjects. The 6 substances with
the highest reactivity following FM were Lyral(R) (2.7%), citral (1.1%),
farnesol P (0.5%), citronellol (0.4%), hexyl cinnamic aldehyde (0.3%), and
coumarin (0.3%). 41 (2.2%) of the patients reacted only to materials of
series I and not to FM. 6.6% of 1855 patients gave a history of adverse
reactions to fragrances which was classified as certain. This group reacted
to FM only in 41.1%, to series I and FM in 12.0% and to series I only in
7.2%. 74.3% of the 39 patients reacting to both FM and 1 of the materials
of series I had any type of positive fragrance history, which was
significantly higher in comparison to those with isolated reactions to
series I (53.6% of 41), p = 0.04. The study identified further sensitizers
relevant for patch testing of patients with contact dermatitis, of which
Lyral(R) is the most important single chemical.

PMID: 12423404 [PubMed - as supplied by publisher]


The main page:

Opinion concerning the 1st update of the inventory of ingredients employed
in cosmetic products section II : perfume and aromatic raw materials
(adopted by the SCCNFP during the plenary session of 24 October 2000)(934KB)


Just some snippets.  IFRA recommends adding antioxidants to several
fragrance chemical that are known to oxidize quickly!

Common Name: 3-CARENE
EINECS No.: 236-719-3
CAS Registry No: 13466-78-9
Chem. Name: 3,7,7-Trimethylbicyclo[4.1.0]hept-3-ene.
Restrictions: Essential oils and isolates (e.g. 3-carene) derived from the
Pinaceae familiy,
including Pinus and Abies genera, should only be used when the level of
peroxides is
kept to the lowest possible level, for instance by adding antioxidants at
the time of
production. Maximum peroxides content 10 mmoles/liter

Common Name: CITRAL
EINECS No.: 226-394-6
CAS Registry No: 5392-40-5
Chem. Name: 3,7-Dimethyl-2,6-octadienal, mixture of cis- and trans-isomers
(Neral and Geranial
Restrictions: Only in conjunction with 25% its weight of D-Limonene or
mixed with citrus
terpenes or ? -pinene.


Common Name: D-LIMONENE
EINECS No.: 227-813-5
CAS Registry No: 5989-27-5
Chem. Name: (R)-p-Mentha-1,8-diene.
Restrictions: To be used in conjunction with antioxidants. Upper limit of
peroxides content 20

Common Name: D-? -PINENE
EINECS No.: 232-087-8
CAS Registry No: 7785-70-8
Chem. Name: (+)-Pin-2(3)-ene.
Restrictions: To be used in conjunction with antioxidants. Upper limit of
peroxides content 10

EINECS No.: 272-842-9
CAS Registry No: 68917-63-5
Chem. Name: Sinpine terpenes and terpenoids.
Restrictions: Essential oils and isolates (e.g. 3-carene) derived from the
Pinaceae familiy,
including Pinus and Abies genera, should only be used when the level of
peroxides is
kept to the lowest possible level, for instance by adding antioxidants at
the time of
production. Maximum peroxides content 10 mmoles/liter

EINECS No.: 232-350-7
CAS Registry No: 8006-64-2
Chem. Name: Turpentine, oil. Any of the volatile predominately terpenic
fractions or distillates
resulting from the solvent extraction of, gum collection from, or pulping of
softwoods. Composed primarily of the C10H16 terpene hydrocarbons: ?
-pinene, ? -pinene,
limonene, 3-carene, camphene. May contain other acyclic, monocyclic, or
bicyclic terpenes, oxygenated terpenes, and anethole. Exact composition
varies with
refining methods and the age, location, and species of the softwood source.
Restrictions: the Turpentine oil should only be used when the level of
peroxides is kept to the
lowest possible level, for instance by adding antioxidants at the time of
Maximum peroxides content 10 mmoles/liter


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