8/9/2019 Patente 2

1/9

1 9 3 8 ~

] O U R N A L O f t h e

m e R i c a N c a D e m y O F

e r M a T O L O G Y

V O L U M E 1 2 N U M B E R 1 P a r t 1 J A N U A R Y , 1 98 5

I I I I I I I I I I

O m in u in g m e d i c a l e d u c a t io n

P e r f u m e d e r m a t i t i s

W a l t e r G . L a r s e n , M . D .

Portland OR

The most com m on react ion to fragrance materials seen by pract icing

derma tologists is allergic co nta ct derm atitis. P hotoderm atitis is occasionally

seen, as is co nta ct urticaria, irritation, and depigmentation. Frag rance s are the

leading cause o f al lergic contact dermati tis d ue to cosm et ics . The fragran ce

mix ture can c ause false-positive reactions; the refore, i t is m ore desirable to

tes t with a separate series o f frag ran ce materials. (J AM ACAI~ DERMATOr.

12:1-9, 1985.)

T h e m o s t c o m m o n r e a c t io n s e e n b y p r a c t i ci n g

d e r ma t o l o g i s t s t o f r a g r a n c e ma t e r i a l s i s a l l e r g i c

c o n t a c t d e r ma t i t is . P h o t o d e r m a t i t i s is o c c a s i o n a l l y

seen , as is con tac t u r t i car i a , i r r i t a t ion , and dep ig -

m e n t a t i o n . F r a g r a n c e s h a v e w i d e s p r e a d u s e a n d

a r e f o u n d n o t o n l y i n c o s me t i c s b u t a l s o i n d e t e r -

g e n t s , f a b r i c s o f t e n e r s , t o o t h p a s t e s , s a n i ta r y p a d s ,

e t c . A r e c e n t p r o s p e c t i v e c o s me t i c a d v e r s e r e a c -

t i o n s t u d y s h o w e d t h a t f r a g r a n c e s a r e t h e l e a d i n g

c a u s e o f a l l e r g i c c o n t a c t d e r ma t i t i s d u e t o c o s -

me t i c s . 1 T h e s e c o n d l e a d i n g c a u s e o f a l l e r g ic c o n -

t a c t d e r ma t i t i s w a s p r e s e r v a t i v e s s u c h a s Q u a t e r -

n i u m- 1 5 , i m i d a z o l i d i n y l u r e a , a n d 2 - b r o mo - 2 - n i -

t r o p r o p a n e - l - 3 - d i o l ( Br o n o p o l ) . L a n o l i n a n d i t s

d e r i v a t iv e s r a n k e d t h i r d .

T h e a p p r o x i m a t e c o n c e n t r a t i o n o f p e r f u m e o il s

u s e d i n v a r i o u s p r o d u c t s i s s h o w n i n T a b l e I .

T h e r e a r e o v e r 5 , 0 0 0 f r a g r a n c e ma t e r i a l s in u s e

* ]~ %~o~ Th e CM E article s are ma de

: .~:... ~ e d u ca tio n a l ra nt fr om SyntexPSsibleLaboratories,thrughlne.an

From the D epartment of D ermatology, The Oregon H ealth Sciences

University.

Reprint requests to: Portland Dermatology Clinic , 2250 N. W. Flan-

ders, Portland, O R 97210.

t o d a y . A t y p ic a l c o m p l e t e p e r f u m e m a y c o n s is t o f

t e n t o 3 0 0 s e p a r a t e c o m p o n e n t s . D e f i n i n g t h e

s p e c i f i c o f f e n d i n g a l l e r g e n s c a n , t h e r e f o r e , b e

diff icul t .

F r a g r a n c e m i x t u r e

T h e f r a g r a n c e m i x t u r e is a c o m b i n a t i o n o f th e

m o s t c o m m o n f r a g r a n c e a l l e r g e n s d e t e c t e d o v e r

t h e l a s t s e v e r a l y e a r s . I t c o n s i s t s o f t h e f o l l o w i n g

e i g h t c h e m i c a l s , a t a 2 c o n c e n t r a t i o n i n p e t -

r o l a t u m : c i n n a m i c a l c o h o l , c i n n a m i c a l d e h y d e ,

e u g e n o l , i s o e u g e n o l , h y d r o x y c i t r o n e l l a l , o a k m o s s

a b s o l u t e , g e r a n i o l , a n d a l p h a a my l c i n n a mi c a l -

c o h o l ( F ig . 1 ). R e c e n t i n t r o d u c t i o n o f t h i s s c r e e n -

i n g mi x t u r e h a s f a c i l i t a t e d t e s t i n g f o r f r a g r a n c e

s e n si ti v it y . B a l s a m o f P e r u i s a m a r k e r o f f ra -

g r a n c e s e n s i t i v i ty a n d i s p o s i t i v e i n a b o u t 5 0 o f

c a se s o f p e r f u m e a l le r g y .

M u c h o f t h e b a c k g r o u n d t e s t i n g f o r t h e f r a -

g r a n c e m i x t u r e w a s p e r f o r m e d u s i n g t h e f r a g r a n c e

c o m p o n e n ts f r o m t h e p e r f u m e i n M y c o l o g c r e a m

( T a b le I I ) ) '3 T h e p e r f u m e m i x t u r e w i l l b e m o d -

i f i e d a s n e w f r a g r a n c e a l l e r g e n s a r e d e f i n e d . O n e

p r o b l e m w i t h t h e p e r f u m e m i x t u r e i s t h a t s o m e

f a l s e - p o s i t i v e i r r i t a n t r e a c t i o n s o c c u r , e s p e c i a l l y

8/9/2019 Patente 2

2/9

Larsen

Journal of the

American Academy of

Dermatology

a b l e

I . A p p r o x i m a t e c o n c e n t r a t i o n s o f

p e r f u m e s i n v a r i o u s p r o d u c t s

Mask ing per fum es 0 .1% or l es s

Cosm etics 0 .5 %

Colognes 4 .0%

Toilet wa ter 5 .0%

Perfumes 20 .0%

w i t h t h e e x c i t e d s k i n s y n d r o m e ( E S S ) , i . e . , t h e

a n g r y b a c k s y n d r o m e . W h e n t hi s o c c u r s , i t i s

i mp o r t a n t t h a t t h e p a t i e n t ' s s k i n b e a l l o w e d t o r e -

t u r n t o n o r m a l a n d t h a t t h e p a ti e n t b e r e t e s t e d w i t h

t h e p e r f u m e m i x t u r e s e v e r a l w e e k s o r m o n t h s

l a t e r .

I f a p o s i t i v e r e s p o n s e t o t h e f r a g r a n c e mi x t u r e

o c c u r s , t h e e i g h t c o m p o n e n t s s h o u l d b e t e s t e d

s e p a r a t e l y i n o r d e r t o d e t e r mi n e t h e i n c i t i n g a l -

l e r g e n . T h e a l l e r g e n s o f th e f r a g r a n c e m i x tu r e a r e

r e a d i l y a v a i l a b l e . * T h e f r a g r a n c e m i x t u r e d e t ec t s

p o s s i b l y 7 0 % t o 8 0 % o f f r a g r a n c e s e n s i ti v i ty ,

l e a v i n g 2 0 % t o 3 0 % u n d e t e c t e d . T h e r e f o r e , i n a

p a t i e n t w h o i s p e r f u m e - s e n s i t i v e b u t h a s a n e g a -

t i v e r e a c t i o n t o t h e f r a g r a n c e mi x t u r e , i t i s n e c e s -

s a r y t o o b t a in t h e c o m p o n e n t s o f t h e o f f e n d in g

p e r f u me a n d t o t e s t t h e c o mp o n e n t s i n o r d e r t o

d e t e r m i n e t h e f r a g r a n c e a l le r g en . T h e e a s ie s t

m e t h o d i s t o a s k t h e c o s m e t i c c o m p a n y f o r s ev e r al

p a r t it i o n s o f t h e f r a g r a n c e a n d to b r e a k d o w n t h e

p a r t i t i o n s t h a t a r e p o s i t i v e u n t i l t h e r e s p o n s i b l e

a l l e r g e n o r a l I e r g e n s a r e d e t e r mi n e d . Mo s t c o s -

m e t i c a n d f r a g r a n c e c o m p a n i e s a r e n o w c o o p e r a -

t i v e i n t h i s e n d e a v o r .

M o s t p e r f u m e s c a n b e t e s te d s a f e ly i n a c o n c e n -

t r a t i o n o f 1 0 % t o 3 0 % i n p e t r o l a t u m o r a l c o h o l .

H o w e v e r , i n d i v id u a l c o m p o n e n t s s h o u l d b e d i lu t e d

t o a c o n c e n t r a t i o n o f 1 % t o 5 % i n p e t r o l a t u m o r

a l c o h o l ( s e e A p p e n d i x ) . A v a i la b l e p e r s o n n e l i n

i n d u s t r y a r e l i s t e d i n a g u i d e p u b l i s h e d b y t h e

C o s m e t i c s , T o i l e t r y a n d F r a g r a n c e A s s o c i a ti o n en -

t i tl e d , C o s m e t i c I n d u s t r y o n C a ll . t

Ca l n a n a n d a s s o c i a t e s 4 t e s t e d 2 ,4 6 1 p a t i e n ts a n d

f o u n d t h e f r a g r a n c e m i x t u r e p o s i t i v e i n 7 % ; m o s t

Tro-Labs, Hermal-Chemie Kurt Herrmann, P.O.B. 1228, D-2057

Reinbek

b. Hamburg, Germany; AmericanAcademy of Dermatol-

ogy, 1567 Maple Ave., Evanston, IL 60201; Hollister-StierLab-

oratories, Box 3145 T.A., Spokane, WA 99220.

tCosmetics, Toiletry

and Fragrance

Association, 1110 Vermont

Avenue N.W . Washington DC 20005.

a b l e

I I . I n g r e d ie n t s o f M y c o l o g c r e a m p e r f u m e

Hydroxyci t ronel lal

Citral pure

Petitgrain Cordillera

Linalyl formate

Lim e distil led

Anisyl alcohol

Citronellal extra

Orange Sweet Cal ifornia

Terpin yl acetate

Cinnamic alcohol

Resinoid labdanum in benzyl benzoate

Terpineol prime

Mo usse d 'Arb re A bsolute (oakmoss absolute)

Gardinol

Acetophenone extra

Musk T Special

Lovage Extra, Oil

Orange Terpenes

Linalyl acetate

Alpha am yl cinnamic alcohol

Sandalwood

Benzyl acetate extra

Patchouli oil

Brazilian bois de rose oil

Geranium bourbon

Lavandin

Coumarin in benzyl alcohol

Ben zyl alcohol

r e a c t i o n s w e r e r e l e v a n t. T h e y a l so d e t e r m i n e d th e

n u mb e r o f p a t i e n t s r e a c t i v e t o t h e i n d i v i d u a l c o m-

p o n e n t s ( T a b l e I I I ) .

e s t i n g t o i n d i v i d u a l f r a g r a n c e m a t e r i a l s

Be c a u s e o f t h e p r o b l e m o f ir r i ta n t , f a l s e - p o s i t iv e

r e a c t i o n s t o t h e p e r f u me mi x t u r e , i t i s c u r r e n t l y

c o n s i d e r e d mo r e a p p r o p r i a t e t o te s t w i t h a p e r f u m e

s c r e e n i n g s e r i e s ( T a b l e I V ) . S i n c e f r a g r a n c e a l -

l e r g y i s s u c h a n i mp o r t a n t p a r t o f d e r ma t o l o g i c

p r a c t i c e , a d d i n g a f e w e x t r a a l l e r g e n s s h o u l d b e n o

b u r d e n i n r o u t i n e t e s ti n g . Pe r f u me s e n s i t iv i t y i s a

c o m m o n c a u s e o f u n s u s p e c t e d a l l e r g y .

T h e Re s e a r c h I n s t i t u t e f o r F r a g r a n c e Ma t e r i a l s

( RI FM) w a s e s t a b l i s h e d b y t h e f r a g r a n c e i n d u s t r y

t o g a t h e r d a t a i n o r d e r t o e v a l u a t e s a f e t y o f f r a -

g r a n c e m a t e r i a l s . T h e y h a v e p u b l i s h e d m o n o -

g r a p h s o n f r a g r a n c e r a w ma t e r i a l s . * T h e I n t e rn a -

t i o n a l F r a g r a n c e R e s e a r c h A s s o c i a t i o n ( I F R A ) t

RIFM, 375-SylvanAve., Englewood, NY 07632.

tIFRA, 8, rue Charles-Humbert, CH-1205, Geneva, Switzerland.

8/9/2019 Patente 2

3/9

V o l u m e 1 2

N u m b e r 1 P a r t 1

J a n u a r y 1 9 8 5

Perfume dermatitis

Ta bl e I I I . Pe r f u me mi x t u r e r e s u l t s

J a n u a r y 1 9 7 9

[

M a r c h

1980 I

T e s t e d P o s i t i v e P e r c e n t

Perfume mixture 2 ,46[ 172 7

Cinnamic aldehyd e 94 4

Cinnam ic alcohol 61 2

Isoeugenol 48 2

Oakrnoss 29 1.2

Eugenol 25 1

Geraniol 7 0.2

Hydrox ycitronellal 36 1.4

Alpha am yl cinnamic 5 0.2

alcohol

w a s f o u n d e d i n 1 97 3 t o e n s u r e t h e s a f e t y -i n - u s e o f

f r a g r a n c e ma t e r i a l s a n d t o c o l l a b o r a t e i n t h e d e -

v e l o p me n t o f i n t e r n a t i o n a l p r a c t i c e s a n d r e g u l a -

t io n s a s t o t h e u s e o f f r a g r a n c e s i n c o n s u m e r p r o d -

u c t s. I FRA h a s a d o p t e d a Co d e o f P r a c t i c e f o r

t h e F r a g r a n c e I n d u s t r y t o g u id e a ll m e m b e r s o f

the indus t ry in eva lua t ing the i r own in t e rna l p ro -

c e d u r e s a n d c o n t r o l s w i t h t h e u l t i ma t e a i m o f p r o -

v i d i n g s a f e f r a g r a n c e s . T h e y p r o v i d e i n d u s t r y

gu ide l ines to res t r i c t i ng red ien t usage a f t e r t he sc i -

e n t i f i c a d v i s o r y c o mmi t t e e r e v i e w s i n f o r ma t i o n

f r o m R I FM , a n d t h e y a l s o p r o v i d e in d u s t r y la b o r a -

t o ri e s a n d a c a d e m i c r e se a r c h .

i n n a m i c al c o h o l a n d e i n n a m l c a l d e h y d e

T h e s e t w o c o m m o n l y u s e d f r a g ra n c e m a te r ia l s

a r e w e l l - k n o w n a l le r g e n s . C i n n a mi c a l d e h y d e a n d

a l c o h o l a n d c h e mi c a l l y r e l a te d c o mp o n e n t s a r e

used p r imar i ly as f l avor ing agen t s , as wel l as

f r a g r a n c e s . T h e y a r e u s e d i n b e v e r a g e s ( c o l a ) ,

v e r mo u t h s , b i t t e r s , c h e w i n g g u ms , mo u t h w a s h e s ,

to i l e t soaps , and too thpas tes . San i t a ry napk in

d e r ma t i t i s d u e t o c i n n a mi c a l c o h o l h a s b e e n r e -

por t ed .

Be c a u s e o f i t s s e n s i t i z i n g c a p a c i t y , I FRA r e c -

o mme n d s t h a t c i n n a mi c a l c o h o l n o t b e u s e d a s a

f r a g r a n c e i n g r e d i e n t a t a l e v e l o v e r 4 % i n f r a -

g r a n c e c o m p o u n d s .

H y d r o x y c i t r o n e l l a l

H y d r o x y c i t r o n e l l a l i s a f r a g r a n c e w i d e l y u s e d i n

f l o ra l iz i n g p e r f u me m a t e r ia l s . I t ma y a l s o b e f o u n d

as a f rag rance in an t i sep t i cs and insec t i c ides . Th i s

w i d e l y u s e d f r a g r a n c e ma t e r i a l is s y n t h e t i c a n d n o t

f o u n d i n n a t u re .

Ta bl e

I V . P e r f u m e s c r e e n i n g s e ri e s

I . Com mon fragrance allergens

(can be used for routine screening)

I . Cinnamic alcohol 5% petrolatum

2. Cinnamic aldehy de 1%

3. Hydroxy ei t ronel lal 4%

4. Isoeugenol 5%

5. Eugenol 5%

6. Oakmoss absolute 5%

II. Less comm on fragrance al ler-

gens

7. Alpha am yl cinnam ic 5%

alcohol

8. Geraniol 5%

9. Benzyl sal icylate 2%

10. San dalwo od oil 2%

11. Anisy l alcohol 5%

12. Ben zyl alcohol 5%

13. Coum arin 5%

III. Photoallergen

14. Mu sk ambret te 5%

(also a co ntact allergen)

I s o e u g e n o l a n d e u g e n o l

T h e s e t w o c o m m o n a l l e r g e n s d o n o t n e c e s s a r il y

c r o s s - r e a c t. E u g e n o l i s f r e q u e n t l y u s e d i n t o o th -

a c h e d r o p s , i n h a l a n t s , a n d a n t i s e p t ic s . B e c a u s e o f

i t s s e n s i t i z i n g c a p a c i t y , I FRA r e c o mme n d s t h a t

i s o e u g e n o l n o t b e u s e d a t a l e v e l o v e r 1 % i n a

c o m p o u n d . P e r f u m e r s h a v e h a d a d i f f i c u l t t i m e

t ry ing to f ind a subs t i tu t e fo r th i s very va luab le

mater i a l .

O a k m o s s a b s o l u t e

O a k mo s s a b s o l u t e i s a n a t u r a l p r o d u c t d e r i v e d

f r o m a t r e e l i c h e n . A t r a n o r i n i s p r e s e n t i n o ak _mo ss

t h at is m a d e f r o m o a k m o s s a n d t re e m o s s . 5 C o n -

t a c t w i t h o a k m o s s p e r f u m e s a n d l i ch e n s i n n a tu r e

m a y c a u s e a t r a n o r in a l l e r g y . O a k m o s s a b s o l ut e is

a c o m m o n l y u s e d f r a g r a n c e m a t e r i a l in a f t er s h a v e

lot ions .

B e n z y l

a l c o h o l

Be n z y l a l c o h o l i s a f r a g r a n c e i n g r e d i e n t t h a t i s

a l so u s e d a s a n a n t i s e p t i c t o p i c a l l y a n d a s a p r e s e r -

v a t i v e i n i n j e c t a b l e me d i c a t i o n s .

M u s k

a m b r e t t e

M u s k a m b r e t t e i s a s y n t h e t i c c h e m i c a l th a t h a s

b e e n u s e d w i d e l y f o r t h e t a s t 6 0 y ea rs .O I t s u s e i n

8/9/2019 Patente 2

4/9

arsen

J o u r n a l o f t h e

A m e r i c a n A c a d em y o f

D e r m a t o l o g y

n

e s s e n t i l

o i l f r om

a l ichen

F _.= _ . . - c o c - - c - c . o . ~ = = ~ c . o -

o k m o s s c i n n a mi c c i n n a m i c a l p h aa m y l

bsolu te ldehyde a lcoho / c innam ic lcoh o l

H

c = c H c H o H c H

H O H H O ~ ~ ~ L o c H = O C H =

. ~ H OH OH

ger n io l h y d r o x y c i t r o n e l la J is o e u g e n o l e u ge n o~

Fig. 1. The eight com ponents of the fragrance m ixture.

f r a g r a n c e s , s o a p s , d e t e r g e n t s , c r e a m s , l o t i o n s ,

a n d d e n t i f r i c e s i n t h e Un i t e d S t a t e s a m o u n t s t o

a b o u t 1 0 0 , 0 0 0 p o u n d s p e r y e a r . T h is n i t r o m u s k

c o m p o u n d i s u s e d a s a fi x a ti v e in p e r f u m e f o r m u -

l a t i o n s in c o n c e n t r a t i o n s f ro m 1 t o a s h i g h a s

1 5 .

i n 1 9 7 8, L a r s e n r e p o r t e d t h e f ir s t c a s e o f p h o -

t o a l l e r g i c c o n t a c t d e r m a t i t i s t o m u s k a m b r e t t e . *

T h e p a t ie n t u s e d a w e l i - k n o w n a f t e r s h a v e lo t i o n

a n d b r o k e o u t w i t h a s e v e r e d e r m a t i ti s o n t h e s u n -

e x p o s e d a r e a s o f t h e f a c e a n d n ec k . S i n c e t h a t ti m e

t h e r e h a v e b e e n n u m e r o u s r e p o rt s o f p h o t o s e n s i -

t i v i t y t o m u s k a m b r e t t e . ~ I n a d d it i o n, m u s k a m -

b r e t t e c a n a l s o c a u s e n o n p h o t o a l l e r g i c c o n t a c t

d e r m a t i t is . H a r b e r s e n s i t i z e d g u in e a p i g s t o m u s k

a m b r e t t e ; h o w e v e r , K l i g m a n w a s n o t a b l e t o s e n -

s i t i z e h u m a n s ? T o d a t e a l m o s t a l l c l i n i c a l c a s e s

h a v e b e e n m a l e . A p p a r e n t l y p u t t in g a f t e r s h a v e lo -

t i o n o n a re c e n t l y s h a v e d f a c e a n d g o i n g o u t d o o r s

i s a n a l o g o u s t o a c o n t i n u o u s d a i l y p h o t o m a x i -

m i z a t i o n t e s t . M u s k a m b r e t t e s h o u l d b e a c o m p o -

n e n t o f a n y p h o t o p a t c h t e st in g s e r i e s ,

I F R A r e c o m m e n d s t h a t m u s k a m b r e t t e no t b e

u s e d a s a f r a g ra n c e i n g r e d i e n t a t a l e v e l o v e r 4 i n

f l a g r a n c e c o m p o u n d s . T h e y fu r th e r r e c o m m e n d

Larsen WG: Photoal lergy to musk ambret te found in an aftershave

lo t ion . Presen ted a t the An nual Meet ing of the Am erican Academ y

of Dermato logy , San Francisco , CA, December, 1978 .

t h a t m u s k a m b r e t t e n o t b e u s e d a t a l e v e l o v e r

O . 1 i n f r a g r a n c e c o m p o u n d s i n t e n d e d f o r u s e in

a f t e r s h a v e p r o d u c t s .

6 Methyleoumarin

6 - M e t h y l c o u m a r i n i s a s y n t h e t i c c o m p o u n d

s t ru c t u ra l l y r e l a t e d t o t h e fu ro c o u m a r i n s . S e v e ra l

y e a r s a g o a n e p i d e m i c o f p h o t o d e r m a t i t i s o c c u r r e d

i n p e o p l e u s i n g a p o p u l a r s u n s c r e e n w i t h a n i n -

c r e a s e d l e v e l o f 6 - m e t h y l c o u m a r i n . 9 T h e r e a c t io n

o c c u r r e d pr i m a ri l y i n w o m e n a n d d e v e l o p e d

wi t h i n s e v e ra l h o u r s a f t e r t h e y a p p l i e d t h e s u n t a n

l o t i o n a n d w e n t i n t o t h e s u n . T h e F D A r e c e i v e d

m a n y c o n s u m e r c o m p l a i n t s , a n d it in i t ia t e d a s h e l f

r e c a l l o f a l l s u n t a n p ro d u c t s c o n t a i n i n g t h i s i n g re -

d i e n t. 1 S u b s e q u e n t p h o t o t e s t i n g s u g g e s t e d t h a t

6 - m e t h y l c o u m a r i n i s i n d e e d a p o t e n t p h o t o s e n s i t i -

z e r , a t l e a s t u n d e r t h e c o n d i t i o n s o f t h i s p a r t i c u l a r

applicat ion. 11

I F R A r e c o m m e n d s t ha t 6 - m e t h y l c o u m a r in a n d

a l so 7 - m e t h y l c o u m a r i n n o t b e u s e d a s a f r a g r a n c e

i n g re d i e n t .

Versalide

( A E T T )

V e r s a l i d e ( A E T T ) i s a T e t r a l i n m u s k w i d e l y

u s e d a s a m u s k f i xa t iv e in m a n y c o s m e t i c s , i n c lu d -

i n g s o a p s , c o l o g n e s , a n d a n t i p e r s p i r a n t s . I t f o u n d

w i d e u s e a s a m a s k i n g a g e n t i n n o n s c e n t e d a n t i -

p e r s p ir a n t s. S e v e r a l y e a r s a g o , A v o n t o x i c o l o g i s ts

8/9/2019 Patente 2

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Volume 12

Number 1, Part 1

January, 1985

Perfume dermatitis

d i s covered t ha t , du r i ng rou t i ne de rm al t e s t s w i t h

ra t s expo s ed t o pe r fum e o i l , t he s k i n and in t e rna l

o rgans o f t he r a t s deve l oped a b l ue co l o r . The

c e n t r a l n e r v o u s s y s t e m w a s a m o n g t h o s e o r g a n s

s h o w i n g t h e m o s t i n t e n s e c o l o ra t io n . T h e p a t h o -

l og i c change found i n t he ne rvous t i s s ue was de -

m y e l i n i za t i on o f ne rve t r ac ts . 12 Th i s neu ro t ox i c

e f f ec t was r epo r t ed t o t he R es ea rch In s t i t u t e fo r

F rag rance Mat e r i a l s , and t he t wo f r ag rance com -

pan i es t ha t m ad e Ver s a l i de s t opped s upp l y i n g i t

f o r u s e in c o n s u m e r p r o d u c t s . T h e F o o d a n d D r u g

A d m i n i s tr a t i o n (F D A ) t o o k n o a c t io n b e c a u s e t h e

c o m p o u n d w a s n o l o n g e r b e i n g u ti li z e d f o r h u m a n

u s e . I F R A r e c o m m e n d s t h a t V e r sa l id e n o t b e u s e d

i n a n y f r a g r a n c e c o m p o u n d s .

a l s a m o f P e r u

B a l s a m o f P e r u i s i n c l u d e d i n t h e A m e r i c a n

A c a d e m y o f D e r m a t o l o g y * s c r e e n i n g s e r i e s a t a

c o n c e n t r a t i o n o f 2 5 % . M a n y p e o p l e w h o a re

f r ag rance - s ens i t i ve a l s o r eac t t o ba l s am o f P e ru .

Hj o r t h ~3 foun d t ha t m os t m en i n h i s s e r ie s becam e

a l l e rg i c t o ba l s am o f P e ru due t o expos u re t o

m e d i c i n a l b a l s a m o f P e r u , w h e r e a s w o m e n b e -

c a m e a l le r g ic t h r o u g h t h e u s e o f f r ag r a n c e m a t e -

r i a ls . M an y a l l e rgens foun d in pe r fum e s a re e i the r

i ng red i en t s o f ba l s am o f P e ru o r a re c l o s e l y re l a t ed

chem i ca l s . Th es e chem i ca l s i nc l ude benzy l a l -

coho l , benzy l ace t a t e , c i nnam i c a l coho l , c i nnam i c

a l d e h y d e , c i n n a m i c a c i d , e u g e n o l , i s o e u g e n o l ,

a n d o t h e r p r o d u c t s o f c o n i f e r y l a l c o h o l s . I F R A

r e c o m m e n d s t h a t b a l s a m o f P e r u n o t b e u s e d a s a

f r ag rance i ng red i en t . On l y d i s t i l l ed p roduc t s t ha t

have no p o t en t i a l fo r s ens i t i za t i on s hou l d be u s ed .

U n s c e n t e d c o s m e t i c s

T h e p a r a d o x o f c o s m e t i c s t h a t a re l a b e le d u n -

s c e n t e d b u t t h a t i n r e a l it y c o n t a in a m a s k i n g

p e r f u m e h a s b e e n r a is e d . 24 U n s c e n t e d , ' ' m a s k -

i n g p e r f u m e s ar e u s e d t o m a s k t h e f a t ty o d o r o f

s o a p a n d o d o r o f b a s e c h e m i c a l s i n u n s c e n t e d

an t i pe r s p i ran t s and l ub r i can t s . The y a re a l s o u s ed

i n c o s m e t i c s l a b e le d l i g h t l y s c e n t e d a n d t h o se

w i t h n o d i s c e rn i b l e a n d n o n l i n g e r i n g f ra -

g rance . T he f r ag rance m a kes up le s s t han 1% o f

t h e c o s m e t i c .

American Academy of Dermatology, 1567 Maple Ave., Evanston,

IL 60201.

I n c o n s i s t e n c y i n c o s m e t i c l a b e li n g p o s e s a d i -

l e m m a t o t h e d e r m a t o l o g i s t w h o a d v i s e s f ra -

g r a n c e - s e n si t iv e p a t i e n t s t o u s e u n s c e n t e d p r o d -

u c t s. A m a s k i n g f r a g r a n c e u s u a l ly c o n s i s ts o f a

s i n gl e fr a g r a n c e m a t e r i a l o r a c o m p l e t e p e r f u m e a t

a r e d u c e d c o n c e n t r a t i o n o f a b o u t 0 . 0 1 % . S o m e

c o m p a n i e s l i s t t h e i r p r o d u c t a s u n s c e n t e d a n d

i n t h e l i s t o f i n g r e d i e n t s i n c l u d e t h e c h e m i c a l

e t h y le n e b ra s s y la t e ( M u s k T ) . H o w e v e r , m o s t p a -

t ie n t s a n d p h y s i c i a n s w o u l d n o t r e c o g n i z e e t h y l e n e

b ras s y l a t e a s a m as k i ng f r ag rance . There fo re ,

t h e re is m e r i t in i n c l u d i n g w i t h t h e c o m p o n e n t o r

c o m p o n e n t s a m a s k i n g f r a g r a n c e i n th e l is t o f in -

g red i en t s i n pa ren t hes es .

T h e s o l u t io n to t h e m a s k i n g f r a g r a n c e p r o b l e m

i s t o e it h e r ( 1) e l i m i n a t e t h e t e r m m a s k i n g f r a -

g r a n c e o r ( 2 ) u s e a p r o m i n e n t as te r is k b y t h e

t e r m u n s c e n t e d a n d l i st t h e c h e m i c a l s t h at c o n -

s t it u te t h e m as k i ng f r ag rance . 15 I f t he m a s k i ng

s c e n t i s a c o m p l e x f r a g r a n c e , t h e i n c l u s i o n o f a

c o d e n u m b e r w o u l d m a k e i t e a s y f o r th e d e r m a t o l -

o g i s t to r e q u e s t t h e m a s k i n g s c e n t f o r p a t c h t e s t -

i n g . P r o m i n e n t d i s c l o s u r e o f t h e p r e s e n c e o f a

m a s k i n g s c e n t i n u n s c e n t e d p r o d u c t s w o u l d in h e r -

e n t l y i n f o r m t h e p u b l i c o f t h e r e a s o n f o r a m a s k i n g

s c e n t a n d r e d u c e t h e c h a n c e o f c o n s u m e r d e c e p-

t ion .

S u n t a n s a l o n p h o t o d e r m a t i t is

A p a t i e n t d e v e l o p e d a s e v e r e p h o t o d e r m a t i ti s o n

t h e a r m s a n d n e c k a f t e r a p p l y i n g S h a l i m a r p e r -

f u m e a n d g o i n g t o a s u n t a n s a lo n . T h e S h a l i m a r

p e r f u m e u s e d w a s 3 0 o r 4 0 y e a r s o l d a n d a p p a r -

en t l y s t i l l con t a i ned t he pho t o t ox i c o i l o f be r -

g a m o t . A p p l y i n g s o m e r e c e n t l y m a n u f a c t u r e d

S h a l i m a r p e r f u m e a n d g o i n g t o t h e s u n t a n s a l o n

p r o d u c e d n o r e a c t i o n . M o s t p e r f u m e s t h a t c o n t a in

o i l o f b e r g a m o t c o n t a i n t h e b e r g a p t e n - f r e e v a r i e ty ;

t h e r e f o r e , t h e p h o t o t o x i c r e a c t i o n s t h a t w e r e

c o m m o n y e a rs a g o a r e r a r e l y s e e n t o d a y .

Co nt a c t ur t i ca r ia

C on t ac t u r t i ca r i a m ay be a l l e rg i c o r nona l l e r -

g i c . 18 B a l s am o f P e ru and c e r t a i n o f i ts de r i va t i ves

c a n c a u s e n o n a l l e r g i c u rt i ca r i a . T h e c h i e f a g e n t

r e s pon s i b l e fo r t h i s is c i nna m i c a l dehy de , a l -

t h o u g h c i n n a m i c a c i d , b e n z o i c a c i d , a n d b e n z a l -

d e h y d e a r e a l so a c t i v e . T h e m e c h a n i s m o f a c ti o n

i s p r o b a b l y a n o n a l l e r g i c h i s t a m i n e - l i b e r a ti n g e f -

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Larsen

Journal of the

American Academy of

Dermatology

T a b l e

V , S u g g e s t e d r e s t ri c t io n s o n i n g r e d i e n t u s a g e ( I F R A ) *

Limit on concentration

Excluded or product use

1. AE Tr (Ac etyl ethyltetramethyl tetral in)

2. Allanroot oil (elecampane oil)

3 . Anisy l idene ace tone

4 . Benzy l idene ace tone

5. P-Ter t-ButylphenoI

6 . Cyclamen a lcoho l t

7 . Diethyl ma leate

8. Dihydrocoumarin

9. 4 , 6-Dim ethyl-8- t butyl coum arin

10. Dimethylci traconate

11. Ethyl acrylate

12 . Hydroab ie ty l a lcoho l

13. 6- Isopropyl-2-decalol

14 . 7 -Methoxyeoumar in

15. a Methyl anisyl idene acetone

16. 6-Methyl coum arin

17. 7-Methyl coumarin~

18. 4-M ethyl-7 -ethox yt coumarin

19. Methylcrotonate

20. Nitrobenzene

21. Pentyl idene cyelohexanone

22. Balsam of Peru

23. Pseudoionones

2 4 . P s eu d o m e t h y l i o n o n e#

25, Styrax

Use with

quenching agent(s)

5-Acety l - 1 ,1 ,2 ,3 ,3 ,6 -hexa-

methy l indan t

Allylesters$

Angelica root~

B er g am o t o i l t ,

Bit ter orange oi l expressed?

Cassia oi l

Cinnamic alcohol

Cinnamon bark o i l , Cey lon

Cos?us root, essential oil, ab-

solute, and concrete

Cumin o i l t

Lemon o i l co ld expressed t

L ime o i l expressed?

Methyl heptine carbonate

M ethyl N-me thyl anthranilate?

dimethyl anthranilate

Opponax?,l[

Per i l laldehyde

Oi ls f rom Pinacea f ami ly

Propylidene phthal ide

Rue o i l?

Safrole

Musk ambret te?

I soeugeno l

Carvone ox ide

Cinnamic a ldehyde

Cinnamic a ldehyde methy l an -

thranilate Sch if f base

Citral

Farnesol

Pheny lace ta ldehyde

*Adapted from Perf & Flavorist 6:64, 1981,

?M ay possessphototoxic or photoallergic properties.

~:Allylesters may be use d on ly when (the irritant) free allyl alcohol is

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Volume 12

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Perfum e dermatitis

t h e o p e n e p i c u t a n e o u s m e t h o d , h e p r e s e n t e d t h e

d o s e o f a f l a g r a n c e r e q u i r e d t o i n d u c e a n d e l i c i t

s e n s i t i z a t i o n . I n m a n , m o s t f ra g r a n c e a l l e r g y p o -

t e n t i a l i s d o c u m e n t e d w i t h t h e m a x i m i z a t i o n

m e t h o d . 4 H o w e v e r , f a l s e- n e g a t iv e a s s ay s o c c u r

w i t h t h i s m e t h o d d u e t o l i m i t a t i o n o f t h e s it e o f th e

t e s t g r o u p . 19

T h e f r a g r a n c e i n d u s t r y i s c o n s t a n t l y t r y i n g t o

e l i m i n a t e f r a g r a n c e m a t e r i a l s t h a t c a u s e a d v e r s e

r e a c t io n s . T h e I F R A l is t s th e c h e m i c a l s t h e y r e c -

o m m e n d n o t b e u s e d a t a ll a n d p r o v id e s a l is t o f

a p p r o v e d c h e m i c a l s w i t h l i m i t s a n d c o n c e n t r a ti o n s

T a b l e V ) . I f t h e f ra g r a n c e i n d u s t r y f o l l o w s t h e s e

r e c o m m e n d a t i o n s , h o p e f u l l y t h e i n c i d e n c e o f

f r a g r a n c e s e n s i t i v i t y , i n c l u d i n g p h o t o s e n s i t i v i t y ,

w i l l d e c r e a s e .

T h e f u t u r e

W e w i l l n o t l e a r n a b o u t n e w f r a g r a n c e a l l e r g e n s

u n l e s s w e l o o k f o r t h e m b y t e s t i n g a l l c o s m e t i c

a n d t o i l e t r y c a s e s a n d d e t e r m i n e t h e o f f e n d i n g a l -

l e r g e n s . T h i s i s d o n e m o s t e a s i l y b y t e s t i n g t h e

f i n a l f o r m u l a t i o n , e x c e p t w h e n i r r i t a t i n g , a s w i t h

s h a m p o o s . I f th e f i n a l f o r m u l a t i o n i s p o s i ti v e , a U

t h e c o m p o n e n t s , i n c l u d i n g t he f r a g ra n c e , s h o u l d

b e o b t a i n e d a n d t e s t e d s e p a r a t e l y . I f t h e f r a g r a n c e

c o m p o n e n t i s p o s i ti v e , f u r th e r b r e a k d o w n o f t h e

f r a g ra n c e t o i ts i n d i v i d u a l c o m p o n e n t s s h o u l d b e

d o n e i n o r d e r to d i s c o v e r n e w f r a g r a n c e a l l e r g e n s .

M a n y f r a g r a n c e a l l e r g i e s a r e o c c u l t , a n d t h u s

w e s h o u l d l o o k f o r f r a g r a n c e a l l e r g y i n a n y

n o n h e a l i n g , r e c u r r e n t , o r c h r o n i c d e r m a t i t i s .

P r e v e n t i o n

A v o i d i n g f r a g r a n c e d c o s m e t i c s a n d t o il e tr ie s i s

f a i r l y s t r a i g h t f o r w a r d i f p a t i e n t s r e a d t h e l a b e l s .

T h e r e a r e s o m e c o s m e t i c l in e s t ha t a re c o m p l e t e l y

f r a g r a n c e - f r e e , s u c h a s A l m a y . H o w e v e r , t h e r e

a r e n o c o m m e r c i a l s o u r c e s o f p e r f u m e s a n d c o -

l o g n e s w i t h f r a g r a n c e i n g r e d i e n t s o n t h e l a b e l s .

M o s t i n d i v i d u a l c o m p a n i e s w i l l a n s w e r w h e t h e r a

s p e c i f i c f r a g r a n c e d o e s o r d o e s n o t h a v e a g i v e n

c o m p o n e n t .

O n c e f r a g r a n c e s e n s i t i v i t y o c c u r s , i t m a y b e

d i f f i c u l t t o a v o i d f r a g r a n c e s . S i n c e c o s m e t i c l a b e l-

i n g d o e s n o t i n c l u d e f r a g r a n c e c o m p o n e n t l a b el -

i n g , u s e t e s ts m u s t b e d o n e w i t h t h e c o s m e t i c s a n d

p e r f u m e s . M o s t f r a g r a n c e - s e n s i t i v e p a t i e n t s c a n

s a fe l y a p p l y p e r f u m e t o t h e i r c l o t h i n g o r h a i r. A l -

t e r n a te l y , f r a g r a n c e - fr e e c o s m e t i c s c a n b e u s e d o n

t h e s k i n .

D D E N D U M

C i n n a m i c a l d e h y d e ( c i n n a m a l d e h y d e ) 2 i n p e t -

r o l a t u m i s a m a r g i n a l i r r i ta n t . T h e r e f o r e , t e s t i n g a t 1

i n p e t r o l a tu m m a y b e m o r e a p p r o p r i a te .

REF ERENCES

1, Eiermann H J, Larsen WG , M aibach HI , Tay lor JS: Pro-

spect ive s tudy of cosm et ic reac t ions ; 1977-1980. J AM

ACAD DBRMATOL6: 909 - 917 , 1982 .

2 , Larsen WG: Al lerg ic contac t dermat i ti s to the per fum e in

M ye o l og c r e a m. J AM ACA D DERMATOL 1 : 131 - 133 ,

1979.

3 . Larsen WG: Perfum e dermat i t i s . A rch Derm atol 113:

623-626, 1977.

4 . Ca l na n CD, Cr on i n E , Ryc r o f t R : A l l e r gy t o pe r f ume

ingredients. C on tac t Dermatit is 6:500- 501 , 1980.

5 . Thu ne P, Solberg Y, M cFadd en N: Perfume a l le rgy due

to oak mos s and other l ichens . Contac t Dermati ti s

8 :396-399, 1982.

6 . Opdyke DL: M us k a m br e t te . M onogr a phs o f f r a g ra nc e

raw materia ls . Foo d Cosm et Tox icol 13:875, 1975.

7 . Raugi GH, Stor rs FJ , Larsen WG: Photoal lerg ic contac t

dermat i t i s to men ' s per fumes . Contac t Dermat i t i s :

251-260, 1979.

8 . Koc he ve r r E , Za l a r GL , E i nb i nde r J , Ha r be r LC: As s a y

of contac t photosens i t iv i ty to musk ambrette in guinea

pigs . J Inves t Dermatol 73:144-146, 1979.

9 . J a c ks on RT , Ne s b i t t L T J r , De Le o VA: 6 -

Me thylcoumar in ph otocon tae t dermat i ti s . J AM ACAD

DERMATOL 2:12 4-1 27, 1980.

10 . E i e r ma nn HJ : Re gu l a t o r y i s s ue s c onc e r n i ng AETT a nd

6-MC . Contac t Derm at i t is 6 :120-1 22, 1980

11. Kaidbey KH , Kl igm an AM : Ident if ica tion o f topica l pho-

tosens it iz ing agents in humans . J Inves t Dermatol

70:149-151, 1978.

12 . Spe nc e r PS , S t e r ma n AB, Hor oup i a n D : Ne u r o t ox i c

changes in ra ts exposed to the f ragrance compound

acetyI e thyl te t ramethyl te t ra l in . Neu rotoxicolo gy 1:

221-238, 1979.

13. Hjor th N: Eczematous a l le rgy to ba lsams. Al l ied per -

fum es and f lavor ing agents wi th specia l re ference to ba l -

s a m o f Pe r u , A c t a De r m Ve ne r e o l ( S toc kh ) 41 ( s upp l

46) :102, 1961.

14. Li t t J : Unsc ented f ragrance . J AM ACA D DERMATOL

2:525 , 1980. (Current issues . )

15. L arsen W G: R esponse . I AM ACAD DRMATOL 2:526,

1980. (Cu rrent i ssues . )

16 . Von Kr ogh G , Ma i ba c h HI : The c on t a c t u r t i c a r i a s yn -

drome, in Marzul l i FN, Maibach HI , edi tors : Der-

matotoxicology, ed . 2 . New York 1983, Hemisphere

Publ ishing Co. , pp . 301-322.

17. M eDanie l W R, Ma rks JG: Co ntac t ur ticar ia due to sen-

s i t iv i ty to spray s tarch . Arch Dermatol 115:628, 1979.

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8 L a r s e n

Joutalal-of the

Amer ican Academ y o f

Dermatology

18, Klejak W: Allergic contact derm atitis in the guinea pig,

in

Marzull i FN , Maibach HI, editors: Dermatotoxicol-

ogy, ed. 2. N ew York, 1983 , Hem isphere Publishing

Co., pp. 193-236.

19. M arzulli F, M aibaeh HI : Contact allergy: Predictive test-

ing of fragrance ingredients in humans by draiz6 and

maximization methods. I Environ Pathol Toxicol 3:

235-245, 1980.

20. Fisher

AA:

Patch testing w ith perfume ingredients. Con-

tact Dermatitis 1:166-168, 1975.

A p p e n d i x

I . P e r f u m e i n g r e d i e n t s , p a t c h t e s t

c o n c e n t r a ti o n s , a n d v e h i c l e s *

Concentration

Cosmetic ingredient and vehic le

Acac i a (gum arab i c) as i s

A c r y l i c m o n o m e r 1 0 o o

Al deh yde C-10 10 DE

Al deh yde C-11 as i s 10 D E

A l d e h y d e C -1 2 L a u f i c 1 0 D E

Al m ond o i l as i s

A l p h a a m y l c i n n a m i c a l d e h y d e 1 p e t

A l p h a m e t h y l i o n o n e 1 p e t

Al pha p i nene 1 pe t

Alp ha terpineol 5 oo

A l u m i n u m c h l o r h y d r o x i d e 1 0 a q s o l

p -an i sa l dehyde 1 pe t

An i se o i l 25 co

Bal m , o i l o f 1 pe t

Bal sam o f Peru 25 pe t

Bal sa m o f To l u 1 a l c

Bay , o i l o f 1 pe t

B a y r u m a s i s

Benzi l dyene ace t one 5 pe t

Benzo i n 10 a l e

Ben zoy l perox i de 1 pe t

Be nzy l acetate as i s

Ben zy l a l coho l 5 pe t

Ben zy l benzoat e 5 pe t

Ben zy l sa l icy l a te 2 pe t

Bergam ot , o i l o f . 10 pe t

B i t t e r a l mond , o i l o f 10 oo

Bl ancopho r 0 .1 pe t

b -Bu t y l -hydroxyan i so l 5 pe t

b -Bu t y l -hydrox y t o l uene 10 pe t

B u t y l a t e d h y d r o x y t o l u e n e 1 0 D E

Cana ga o i l 2 pe t

Carn at ion oi l 10 aq sol

Carophy l l ene 5 pe t

Cass i e syn t he t i que 10 DE

Cedar t one V as i s

Cedarw ood o i l 10 oo

Cet av l on 5 pe t

Cet y l a l coho l 30 pe t

acet

Acetone;ale: alcohol; aq: aqueous;as is: undiluted;BA: benzyl

alcohol; BL: butyrolactone;co: castoroil; DE: de tyl extra (isopropyl

palmitate); oo: olive oil; p et: pe trolatum;sol: solution,

*Adapted from Fisher AA: C ontactDerm atitis 1:166-168, 1975.

A p p e n d i x

I .

C o n t d

Concentration

Cosmetic ingredient and vehic le

Ci nnarna t es (2 -e t hoxyet hy l -p - 1 pe t

m e t h o x y )

C i n n a m i c a c i d 5 p e t

C i nnam i c a l coho l 5 pe t

C i n n a m i c a l c o h o l s t y r a x t y p e 5 p e t

C i n n a m i c a l d e h y d e 1 p e t

C i n n a m o n o i l 0 . 5

C i n n a m y l a l c o h o l 5 p e t

Cis-~-terpineol 2 5 i n B L

Ci t r ace t a l paren t o 10 D E

Ci t ral o i l 1 pet

Ci t r ic acid 1 aq sol

C i t ron , o i l o f 1 pe t

C i t rone l l a , o i l o f 1 pe t

Ci t ronel lo l 1 pet

C i t rone l l y l oxya ce t a l deh yde 1 pe t

C l ove o i l 1 pe t

C o n i f e r y l b e n z o a t e i p e t

C o u m a r i n 5 p e t

p - C y m e n e 1 p e t

8 -Cad i nene 1 pe t

Del t y l ex t r a 5 pe t

Di e t hy l ph t ha l a t e 2 pe t

3 , 7 - D i m e t h y l - l - o c t a n o l

Di m et hy l ph t ha l a t e 2 pe t

Essen t i a l o i l s 1 a l e o r 2

pe t

Es t r ad i o l 5 pe t

Et hy l a l coho l as i s

Et hy l van i l l i n 10 pe t

Euca l yp t us , o i l o f 1 pe t

E u g e n o l 5 p e t

Geran i o l 2 pe t

Gera n i um o i l 2 pe t

Gi nger , o i l o f 1 pe t

Gum (s) as i s

Gy l an as i s

Ham amel i s v i rg in iana

5 aq so l

H e x y l c i n n a m i c a l d e h y d e 2 p e t

Hi b i t ane d i b l ue 1 pe t

4 - H y d r o x y a z o b e n z e n e c a r b o x y l ic 2 p e t

ac i d

Hyd roxyci t rone l l a l 5 pe t

continued

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Volume 12

Number 1, Part 1

January, 1985

P e r f u m e d e r m a t i t i s 9

A p p e n d i x I .

C o n t d

C o n c e n t r a t i o n

C o s m e t i c i n g r e d i e n t a n d v e h i c l e

a - I r i s o n e a s i s

I s o a m y l s a l i c y la t e 5 % p e t

I so b u ty l sa l i cy l a t e 5 % p e t

I s o p r o p y l m y r i s t a t e 1 0 % a l e o r 2 %

p et

I so p ro p y l q u in o lo n e as i s

J a m i n o i l 2 % p e t

Jasm in 9 1 4 0 as i s

L a u r e l o i l 2 % p e t

A p p e n d i x I . C o n t d

C o s m e t i c i n g r e d i e n t

C o n c e n t r a t i o n

a n d v e h i c l e

P er fu m es as i s (o p en an d

c lo sed )

Pet i tg rain o i l 10% oo

Pet i tg rain rect i f ied as i s

[3-Phenyl ethy l ac etate 1% pet

[3-Phenyl alcoho l 1% pet

P h e n y l a c e t a l d e h y d e 2 % p e t

P in e o f f p u re

P ip ero n a l (m e th y l i o n o n e) 1 % p e t

L a u r y l a l c o h o l 5 % p e t R h o d a m i n e 5 % p e t

Lau ry l g a l l a t e 5 % p e t Ro se , o i l o f 1 % a l c

L a u r y l s u l f a t e ( a m m o n i u m ) 5 % p e t R o s e o i l B u l g a r i a 2 % p e t

Lav en d er , o i l o f 1 % p e t Ro se 6 2 t e r a s i s

L e m o n , o i l o f 1 % p e t S a n d a l w o o d o i l 2 % p e t

Lem o n g rass , o i l o f 1 % p e t S an d e l a 1 0 as i s

L im o n en e , o i l o f 1 % p e t S assa f r as , o i l o f 1 % p e t

L in a lo o l , o i l o f 1 0 % p e t S esam e o i l 5 % o o

Lin ay l ace t a t e 1 % p e t S p i ce , o i l o f 5 % p e t

M a h o g o n a t e d r a g o c o a s i s S t y ra x e s s e n c e G D 5 % p e t

M e n t h e n y l a c e t a t e a s i s T e r p in e o l e x t r a 2 5 % i n B L

M e t h o x y c i t r o n e l la 1 % p e t T e r p i n o le n e 1 % p e t

Me th y l i o n o n e -y-pu re IF F as i s Te t r a h y d r o m u g u o l as i s

Me th y l sa l i cy l a t e 1 % p e t Th io g ly co l l a t e ( ca l c iu m ) 5 % aq so l

M i n t o i l 1 % p e t T h y m e , o i l o f 2 5 % c o

Mi rb a n e o i l ( n i t ro b en zen e) 2 5 % co

T r a n s . C i n n a m i c

a l d e h y d e 2 % p e t

M u s k a m b r e t t e 5 % p e t T r i e t h a no l a m i n e 5 % p e t

13-Myrcene 1% pet Vani lla (alco hol ic ex t ra ct ) 10% acet

My r i s t y l a l co h o l 5 % p e t Ver sa l id e p r im e 1 0 % p e t

Nero l i , o i l o f 1 0 % o o Verb en a , o i l o f 1 % p e t

Oran g e , o i l o f 1 % p e t Ve t i v e rt r ec t i f i ed as i s

P a t ch o u l i , o i l o f 1 % p e t Ylan g -Y lan g o i l 5 % p e t

P ep p erm in t o i l 1 % p e t

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