Table 13-6: Known prehaptens and prohaptens.
| Fragrance substance |
Activation by air oxidation |
Bioactivation (oxidation) |
Bioactivation (hydrolysis) |
| Cinnamyl alcohol |
|
x |
|
| Eugenol |
|
x |
|
| Eugenyl acetate |
|
x |
x |
| Geranial |
x |
x |
|
| Geraniol |
x |
x |
|
| Geranyl acetate |
x |
x |
x |
| Isoeugenol |
|
x |
|
| Isoeugenyl acetate |
|
x |
x |
| Limonene |
x |
|
|
| Linalool |
x |
|
|
| Linalyl acetate |
x |
|
|
| alpha-Terpinene. |
x |
x |
|
Source:
SCCS, 
Opinion on Fragrance allergens in cosmetic products, page 118
Related publication:
Other Figures & Tables on this publication:
Table 4-1: Ingredients of Fragrance Mix I (FM I; 8% allergens in petrolatum).
Table 4-2: Ingredients of Fragrance Mix II (FM II; 14% allergens in petrolatum).
Table 4-3: Results with screening agents for contact allergy to fragrance ingredients reported since
1999 in patients patch tested for suspected allergic contact dermatitis in Europe: Fragrance Mix “I”
(see Table 4-1). If not given in the publication, the confidence interval (CI) was calculated from the
absolute numbers by the SCCS (§).
Table 4-4: Results with screening agents for contact allergy to fragrance ingredients reported since
1999 in patients patch tested for suspected allergic contact dermatitis in non-European countries:
Fragrance Mix “I” (see Table 4-1). If not given in the publication, the confidence interval (CI) was
calculated from the absolute numbers by the SCCS (§).
Table 4-5: Results with screening agents for contact allergy to fragrance ingredients reported since
1999 in patients patch tested for suspected allergic contact dermatitis: Fragrance Mix “II” (see Table
4-2). The FM II was only conceived in 2005, so results are still sparse). If not given in the publication,
the confidence interval (CI) was calculated from the absolute numbers by the SCCS (§).
Table 4-6: Results with fragrance contact allergy screening agents reported since 1999 in patients
patch tested for suspected allergic contact dermatitis: HICC (5% pet. if not stated otherwise). If not
given in the publication, the confidence interval (CI) was calculated from the absolute numbers by the
SCCS (§).
Table 4-7: Results with fragrance contact allergy screening agents reported since 1999 in patients
patch tested for suspected allergic contact dermatitis: Myroxylon pereirae resin (Balsam of Peru)
(25% pet.). If not given in the publication, the confidence interval (CI) was calculated from the
absolute numbers by the SCCS (§).
Table 4-8: Results with fragrance contact allergy screening agents reported since 1999 in patients
patch tested for suspected allergic contact dermatitis: Oil of turpentine (10% pet.) patients patch
tested for suspected allergic contact dermatitis. If not given in the publication, the confidence interval
(CI) was calculated from the absolute numbers by the SCCS (§).
Table 4-9: Results from patch testing with Fragrance Mix I in different population based groups.
Table 4-10: Results from patch testing with other fragrance allergens in different population based
groups. If not given in the publication, the confidence interval (CI) was calculated from the absolute
numbers by the SCCS (§).
Table 4-11: Extract from ((65) Table 3) regarding the proportion of patients with “present clinical
relevance” (see text) and “past clinical relevance” (criteria not given).
Table 4-12: Extract from ((106) Table 2) on the frequency of positive reactions to fragrance allergens
in patients with vs. without positive patch test reaction to their own deodorant.
Table 4-13: Extract from ((106) Table 2) on the frequency of positive reactions to fragrance allergens
in patients with vs. without positive patch test reaction to their own aftershave, eau de toilette or
perfume.
Table 5-1: Contact allergic reactions to the autoxidised fragrance substances limonene, linalool,
caryophyllene, myrcene and linalyl acetate in consecutive dermatitis patients.
Table 5-2: Contact allergic reactions to limonene, linalool, linalyl acetate and caryophyllene in
consecutive dermatitis patient. Please observe that several studies have been performed using the
test substances without reporting the autoxidation status but it has been intended to be low. For
precise information see the original references.
Table 5-3: Concomitant reactions to fragrance markers: Fragrance Mix I and II (FM I, FM II),
Myroxylon pereire (MP) and to colophonium (coloph.) in the baseline series in patients with positive or
negative patch test reactions to oxidised fragrance substances.
Table 5-4: Mean and median content of isoeugenol and its derivatives in the 29 perfume products.
Table 7-1: Established contact allergens in humans (summary of evaluation as detailed in chapter
6.3). More detailed information forming the basis of this evaluation can be found in Annex I of this
opinion.
Table 7-2: Fragrance substances with positive human data, which are, however, not sufficient to
categorise as “established contact allergen in humans”. More detailed information forming the basis of
this evaluation can be found in Annex I of this opinion.
Table 7-3: Fragrance substances with negative human data, i.e. patch tests of patients with
suspected contact allergy to fragrance ingredients which yielded negative results.
Table 7-4: Fragrance substances lacking human data and used in high volumes according to industry
information.
Table 7-5: Natural extracts classified as established contact allergens in humans (summary of
evaluation as detailed in chapter 6.3). More detailed information forming the basis of this evaluation
can be found in Annex I of this opinion, including variants of botanical nomenclature.
Table 7-6: Natural extracts with positive human data, which are, however, not sufficient to categorise
as “established contact allergen in humans”. More detailed information forming the basis of this
evaluation can be found in Annex I of this opinion.
Table 7-7: Indicative list illustrating natural extracts containing established human allergens or
having R43-lable or positive LLNA, lacking published human data.
Table 8-1: Summary of local lymph node assay (LLNA) data on 66 fragrance substances, based on a
report submitted by the Research Institute for Fragrance Materials, Inc. (RIFM, 2009 (164)) and in
published reviews by Gerberick et al. 2005 (165) and Kern et al. 2010 (166), respectively. EC3 values
(% and M) are given. The order of substances is by decreasing sensitisation potency as assessed by
LLNA EC3 values (lowest EC3 value indicating highest potency).
Table 8-2: Local lymph node assay (LLNA) data on four fragrance substances and one essential oil
before and after air exposure, comparing the sensitisation potency of the pure (not oxidised)
substance with the potency of the oxidised.
Figure 8-1: The distribution of fragrance chemicals and a variety of other chemicals
Table 8-3: Summary of EC3 values for fragrance substances in Table 8-1 and for other substances, all taken from the three references (164-166). The EC3 value intervals for potency categorisation (161, 205) were used for comparison of fragrances substances vs other substances.
Table 9-1: Predicted sensitisers.
Table 9-2: Possible sensitisers.
Table 9-3: Predicted non-sensitisers with no obvious structural alerts.
Table 9-4: Not predictable.
Table 10-1: Presence in children's cosmetics of the 26 fragrance substances that are required to be
labelled in cosmetics (227).
Table 10-2: Usage trends in deodorants of fragrance chemicals that are required to be labelled in cosmetics.
Table 10-3: Frequency of occurrence in consumer products of the 26 fragrance allergens that are required to be labelled in cosmetics and detergents (229).
Table 10-4: Frequency in 516 consumer products of the 26 fragrance substances that are required
to be labelled in cosmetics* (115).
Figure 10-1: Frequency of occurrence in 3,000 consumer products of the 26 fragrance allergens that are required to be labelled in cosmetics and detergents.
Table 10-5: Concentration of Fragrance Mix I ingredients in five prestige perfumes before and
after the regulation of the 26 fragrance allergens.
Table 10-6: Concentrations of Fragrance Mix I ingredients, hexyl cinnamal and coumarin in 22
perfumes marketed as natural cosmetics investigated in 1996.
Table 10-7: Atranol and chloroatranol content in eau de toilette/eau de perfume, investigated in
2004 and in 2007.
Table 10-8: Parts of Annex I to (EC) No 1451/2007 (see above): “Active substances identified as
existing”, if use is ‘perfuming’ or ‘masking’ according to CosIng.
Table 10-9: Result of a Poisson regression analysis of patients tested with the Fragrance Mix
Table 10-10: Association between selected risk factors and positive patch test to
Myroxylon pereirae resin. For full model see (269). Risk quantified with the prevalence ratio (PR) with accompanying 95% confidence interval (CI).
Table 11-1: Current IFRA restrictions based on induction experiments.
Table 11-2: Spearman’s rank correlation between the threshold concentration in the patch test and the repeated open application test for three allergens.
Figure 11-1: The fitted dose-response curve for patch test
Table 11-3: Overview of results of deodorant provocation investigations with different allergens. Frequency in % of test groups, which reacted at different doses of allergen applied in a roll-on deodorant in the axilla, is given in the table.
Table 11-4: Overview of threshold results from clinical studies.
Table 11-5: Concentration limits in different product types based on 0.8 μg/cm2 allergen as a 'generally safe exposure level', if specific dose-response data are unavailable.
Table 11-6: Overview of dose-response studies and thresholds for eight allergens, after (280).
Figure 11-2: The threshold data with 95% confidence intervals from Table 11-6 presented
graphically, after (280).
Figure 11-3: The fitted dose-response curves from the studies in Table 11-6, which are the basis for estimation of the ED10 value, after (280).
Table 11-7: Restriction for HICC independent of the QRA according to (293).
Figure 11-4: Time trend of hydroxyisohexyl 3-cyclohexene carboxaldehyde sensitisation prevalence
Figure 11-5: Prevalence of positive patch test reactions to hydroxyisohexyl 3-cyclohexene carboxaldehyde
Table 13-1: Established contact allergens in humans.
Table 13-2: Fragrance substances categorised as established contact allergens in animals.
Table 13-3: Fragrance substances categorised as likely contact allergens by combination of
evidence.
Table 13-4: Fragrance substances categorised as possible contact allergens.
Opinion on fragrance allergens in cosmetic products
Table 13-5: Established fragrance contact allergens of special concern (single chemicals only).
Table 13-6: Known prehaptens and prohaptens.
