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PERFUMES FROM ANCIENT TIMES TO THE PRESENT

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 PERFUMES
FROM ANCIENT TIMES TO THE PRESENT

Perfume Maker.
Rodolphe Ernst

Medical Research in Biblical Times

Examination of Passages from the Bible, Exactly as Written

Liubov Ben-Nun

NOT FOR SALE

 The present research deals with perfumes. What is the history of
perfumes? What is the composition of perfumes? What are the
various types of perfumes? What are their positive and negative
health effects?
Biblical texts were examined and verses in which perfumes were
described were studied from a contemporary viewpoint.

Author: Dr. Liubov Ben-Nun, Professor Emeritus

Ben Gurion University of the Negev
Faculty of Health Sciences, Dept. of Family Medicine
Beer-Sheva, Israel.

B.N. Publication House. Israel. 2018.

E-Mail: L-bennun@smile.net.il

The Author gains no financial or other benefits.

Technical Assistance: ILana Siskal

NOT FOR SALE

 CONTENTS

MY VIEW 4

FOREWORD 5

INTRODUCTION 9

TERMINOLOGY 11

BIBLICAL VERSES 11

HISTORY 13

SMELL/BODY ODOR 24

PERFUMER 33

PERFUME SELECTION 35

TYPES 37

COMPOSITION OF PERFUMES 41

FRAGRANCE CONCENTRATIONS 55

FRAGRANCE SENSITIZERS 58

HEALTH EFFECTS 66

ADVERSE REACTIONS 67

CONCLUSION 97
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MY VIEW
MEDICINE IN THE BIBLE AS A RESEARCH CHALLENGE

This is a voyage along the well-trodden routes of contemporary

medicine to the paths of the Bible. It covers the connection between
body and soul, and the unbroken link between our earliest ancestors,
accompanied by spiritual yearning and ourselves. Through the verses
of the Bible flows a powerful stream of ideas for Medical Research
combined with study of our roots and the Ancient texts.

The Bible exists as evidence in the Book of Books, open to all

humankind, the text that has been translated into hundreds of
languages and dialects, and remains our eternal taboo.

Many people ask me about the connection between the Bible and
medical science. My reply is simple: the roots of science are buried
deep in the biblical period and I am just the archeologist and medical
researcher. This scientific medical journey to the earliest roots of the
nation in the Bible has been and remains moving, exciting and
enjoyable. It has created a kind of meeting in my mind between the
present and those Ancient times, through examining events frozen in
times.

Sometimes it is important to stop, to look back a little. In real

time, it is hard to study every detail, because time is passing as they
appear. However, when we look back we can freeze the picture and
examine every detail, see many events that we missed during that
fraction of a second when they occurred.

The Book of Books, the Bible, is an essential source for the whole
world.
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FOREWORD
Fragrance preparations or perfumes are used in an increasing
variety of applications, including washing, cleansing, personal care
products, and consumer goods or in applications to modify indoor air.
However, up to now, little is known to the general or scientific public
about their chemical identity and the use pattern of single
substances, not even for high production volume chemicals. Some
toxicological data are published for a comparatively small number of
substances with a focus on sensitization and dermal effects, while
other effects are neglected. Information on ecotoxicity and
environmental fate are rare, especially for long-term exposure. Data
for a detailed hazard and risk analysis are available in exceptional
cases only. According to the current legal situation, fragrance
industry is self-regulated, which means that pre-market risk
evaluation is not required for most fragrances. Odor and the ability
to smell play a major role for wildlife for all taxonomic groups.
Reproductive and social behavior, defense, communication and
orientation depend on volatile compounds which can be identical to
those used in fragrance preparations. The interdisciplinary approach
leads to the question of whether and, if so, to what extent
anthropogenic fragrances may influence life and reproduction of
organisms in the environment. Information from literature on use,
exposure and biological effects was combined to analyze the state of
knowledge. Following an overview of the amounts of fragrances
used in different consumer products and their release into the
environment, the roles of odors in nature are shown for a selection
of compounds. Existing regulation is analyzed to describe the data
basis for environmental risk evaluation. Recommendations for
further action are derived from these findings. Three main results
are elaborated: first, fragrance substances are continuously
discharged in large amounts into the environment, especially via the
waste water. Second, there are some indications of negative effects
on human health or the environment, although the data basis is very
thin due to the self-regulation of the fragrance industry and the
regulatory situation of fragrance substances. Third, many
odoriferous substances used by man are identical to those which are
signal substances of environmental organisms at very low
concentrations, thus giving rise to specific mode of actions in the
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ecosystem. For the adequate risk assessments of fragrances, test

results on their unspecific as well as their specific effects as signal
substances are needed. This would imply prioritization methods and
development of useful test methods for specific endpoints for
appropriate risk assessments. Before a comprehensive testing and
evaluation of results has been finished, a minimization of exposure
should be envisaged. Eco-labeling of products containing acceptable
fragrance ingredients could be a first step and provide consumers
with the respective information. Transparency concerning the
fragrance ingredients used and their biological potency will help to
build up confidence between producers and consumers. The
interdisciplinary approach, bringing together chemical, biological,
toxicological and ecotoxicological data with information provided by
manufacturers and with legal and consumer aspects, offers new
insights into the field of fragrance substances used in consumer
products. The amounts and application fields of fragrance
substances increase while fate and effects in the environment are
hardly known. The legal situation is not suited to elucidate the
effects of fragrances on human health and the environment
sufficiently, especially as it was shown that fragrances may play a
considerable role in the ecosystem on the behavior of organisms.
According to the precautionary principle, the lack of knowledge
should best be tackled by reducing exposure, especially for
compounds such as fragrance substances where no ethical reasons
object a substitution by less hazardous chemicals (1).
Synopsis In the fine fragrance industry, unlike many other fast
moving consumer goods (fmcg) industries, systematic consumer
product-testing has usually been conspicuous by its absence. The
reasons are varied, including perfume's own traditions rooted in
fashion rather than in marketing, the reluctance of perfumers to see
their creations tested, the frequently (and perhaps, surprisingly)
short lead times accorded for new product development and, of
course, costs. When consumer product-testing is carried out, it is
often limited for these same reasons, to 'sniff-testing', which, in the
perfume industry, is equivalent to 'first impression' testing. Such
sniff-testing may not only be unreliable, but perhaps more unreliable
for the perfume category than has been realized hitherto. Reference
is made to two consumer research studies on perfume, a qualitative
project in France, followed by a quantitative exercise in the UK. A
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comparison is made between in-home test and sniff-test results for

the same set of perfumes, which illustrates the limitations of sniff-
testing in general, and the misleading results that it may produce, in
particular. A major implication is that perfume is one product
category which should be tested in extended usage and not just for
'first impressions' (2).
Reliable exposure information for cosmetic and other personal
care products and ingredients is needed in order to conduct safety
assessments. Essential information includes both the amount of
product applied, and the frequency of use. To obtain current data,
studies to assess consumer use practices were undertaken. Six
widely used personal care product types were included in the studies.
Five of the products were cosmetics (spray perfume, hairspray, liquid
foundation, shampoo, and body wash) and one product was a
cosmetic/over-the-counter drug product (solid antiperspirant). Three
hundred and sixty women, aged 19-65 years, who regularly use the
products of interest, were recruited at 10 different geographical
locations within the U.S. The number of recruits was chosen to
ensure a minimum of three hundred completed responses per
product type. Subjects were provided with a new container of the
brand of product they normally use and kept diaries and recorded
detailed daily usage information over a two week period. Products
were weighed at the start and completion of the study in order to
determine the total amount of product used. The geometric mean
and median usage per application, respectively, for the six product
types were: spray perfume, 0.33 g and 0.23 g; hairspray, 2.58 g and
1.83 g (aerosol); 3.64 g and 2.66 g (pump); liquid foundation, 0.54 g
and 0.36 g; shampoo, 11.76 g and 9.56 g; body wash, 11.3g and 9.5 g;
and solid antiperspirant, 0.61 g and 0.45 g. The mean and median
usage per day for the six product types were: spray perfume, 0.53 g
and 0.34 g; hairspray, 3.57 g and 2.71 g (aerosol); 5.18 g and 3.74 g
(pump); liquid foundation, 0.67 g and 0.45 g; shampoo, 12.80 g and
10.75 g; body wash, 14.5 g and 12.9 g; and solid antiperspirant, 0.79 g
and 0.59 g. The mean number of applications per day for spray
perfume, hairspray, liquid foundation, shampoo, body wash, and
solid antiperspirant was 1.67, 1.49 (aerosol) and 1.51 (pump), 1.24,
1.11, 1.37, and 1.3, respectively. The findings provide current
exposure information for commonly used products which will be
useful for risk assessment purposes (3).
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People tend to choose perfumes to complement their body odor.

As kin share some body odor qualities, their ability to select
complementary perfumes for relatives might be higher compared
with selection for nonrelatives. Selection of a perfume for a target
man by himself and by either a familiar but unrelated individual
(girlfriend; Study 1) or a relative (sister; Study 2) was compared.
Target men applied the two perfumes (own or other's choice) to their
axillae and then wore cotton pads for 12 hours. Collected perfume-
body odor blends and perfumes alone were assessed by rater panels.
In Study 1, the blends were rated as nominally more pleasant when
body odors were mixed with the perfumes selected by girlfriends
compared with those selected by target men themselves. In Study 2,
body odors mixed with perfumes selected by sisters were rated
significantly more attractive than those mixed with perfumes
selected by target men. Insignificant differences were found for
attractiveness and pleasantness ratings when perfumes were rated
alone, suggesting that it was the resulting blends that were uniquely
different. The results indicate that sisters might be particularly tuned
to select suitable perfumes for their siblings (4).
Lanca perfume (chloroform/ether) is an inhalant used mainly by
higher social class students in Brazil. In light of the social and
epidemiological features of lanca use, supply, and distribution, this
investigation tests hypotheses about the degree to which use of
inhalant lanca might be occurring in clusters, consistent with social
sharing and diffusion, and might show a direct association with social
rank even within the relatively privileged social context of private
schools in a large mega-city of Latin America. Epidemiologic self-
report survey data were from a large representative sample of urban
post-primary private school students in São Paulo city, Brazil, in 2008.
Newly incident lanca use was studied, first with estimates of
clustering from the alternating logistic regressions (ALR) and then
with conditional logistic regressions to probe into the hypothesized
direct social rank association. ALR disclosed a clustering of newly
incident lanca users within private school classrooms (pairwise odds
ratio [PWOR] 2.1; 95% CI 1.3-3.3; p=0.002) as well as clusters of
recently active lanca use (PWOR 1.9; 95% CI 1.1-3.3; p=0.02).
Occurrence of lanca use within private school classrooms was directly
associated with social rank (odds ratio [OR] 0.2; 95% CI 0.1-0.8;
p=0.03 in the contrast of lowest socio-economic status [SES] versus
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highest SES strata within classrooms). Thereafter, study of other

drugs disclosed similar patterns. In conclusion, the clustering
estimates are consistent with concepts of person-to-person sharing
of lanca within private school classrooms as well as other dynamic
processes that might promote lanca clusters in this context. An
observed direct association with social rank is not specific to lanca
use. Direct SES estimates across a broad profile of drug compounds
suggests causal processes over and above the more specific initially
hypothesized social rank gradients in the lanca diffusion process. A
novel facet of the evidence is greater occurrence of drug use among
the higher social rank private school students, which should be of
interest in the social science community (5).

References
1. Klaschka U, Kolossa-Gehring M. Fragrances in the environment: pleasant
odours for nature? (9 pp). Environ Sci Pollut Res Int. 2007;14 Suppl 1:44-52.
2. Shalofsky I. First impression versus extended usage: a comparison of
product testing methodologies for perfume. Int J Cosmet Sci. 1993;15(2):63-75.
3. Loretz L, Api AM, Barraj L, et al. Exposure data for personal care products:
hairspray, spray perfume, liquid foundation, shampoo, body wash, and solid
antiperspirant. Food Chem Toxicol. 2006;44(12):2008-18.
4. Sobotková M, Fialová J, Roberts SC, Havlíček J . Effect of biological
relatedness on perfume selection for others: preliminary evidence. Perception.
2017;46(3-4):498-515.
5. Sanchez ZM, Noto AR, Anthony JC. Social rank and inhalant drug use: the
case of lança perfume use in São Paulo, Brazil. Drug Alcohol Depend. 2013;131(1-
2):92-9.

INTRODUCTION
My previous Research deals with beauty which is a universal
human experience that accompanied us from the dawn of history (1).
Many beautiful characters lived thousands of years ago, some
hundred years ago. Their beauty is presented in various paintings,
sculptures, and literature. Beauty is the quality of being pleasing,
especially to look at, or someone or something that gives great
pleasure, especially when looking at it. Standards of beauty have
changed over time, based on changing cultural values. However,
although centuries have passed, the beauty of some individuals still
captures our imagination. These fascinating images will remain
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forever in the history of humankind. The research presents the

approach towards beauty and described beautiful characters in
various ancient cultures including biblical time, as well as Egypt,
Greece, Rome, Byzantine Empire, Persia, India, China, Japan, and the
Elizabethan era (1).
An additional research deals with cosmetics (2). Cosmetics have
been part of human life since the dawn of history. The use of
cosmetics is documented in various civilizations in ancient world.
Some products and methods of use are relevant to the modern time.
In ancient cultures, in general, the adverse effects of many
cosmetics were unknown (except toxic Pb present in skin whiteners)
and so women shortened their lives because of the exposure to toxic
elements found in cosmetic products.
In the Bible, there are precise descriptions of various products and
the purposes of their use.
In modern time, the desire for perfect beauty occupied individuals
throughout the world. Although cosmetics, as mentioned in this
research, can provide positive effects there are many dangerous
adverse effects of their usage. Individuals, mostly women, who use
cosmetics, regardless of type, should be aware of side effects that are
detrimental to human health (2).
The present research deals with perfumes. What is the history of
perfumes? What is the composition of perfumes? What are the
various types of perfumes? What are their positive and negative
health effects?
Biblical texts were examined and verses in which perfumes were
described were studied from a contemporary viewpoint.

References
1. Ben-Nun L. Beauty of Humans. In: Ben-Nun L. (ed.). B.N. Publication
House. Israel. Available 2016 at www.Researchgate.net/.
2. Ben-Nun L. Medical effects of Cosmetics. In: Ben-Nun L. (ed.).
B.N. Publication House. Israel. 2016. Available at www.Researchgate.net/.
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TERMINOLOGY
The word perfume is used today to describe scented mixtures and
is derived from the Latin word, "per fumus," meaning through smoke.
The word perfumery refers to the art of making perfumes (1).
Perfume is defined as the scent of something sweet-smelling; a
substance that emits a pleasant odor; especially: a fluid preparation
of natural essences (as from plants or animals) or synthetics and a
fixative used for scenting (2).
Perfume is also defined as a pleasant smelling liquid preparation,
e.g. of floral essences applied to the skin; a sweet or pleasant smell; a
fragrance (3).
Perfume (UK: /ˈpɜːrfjuːm/ U.S.: /pərˈfjuːm/; French: parfum) is a
mixture of fragrant essential oils or aroma compounds, fixatives and
solvents, used to give the human body, animals, food, objects, and
living-spaces an agreeable scent. It is usually in liquid form and used
to give a pleasant scent to a person's body (1,2).
Fragrance is defined as a sweet or pleasant smell; a perfume or
aftershave; the smell of this (3).
In addition, perfume or fragrance is a blend of fragrant oils, aroma
compounds and fixatives to produce a pleasant and soothing scent
for humans and other living objects (4).

References
1. Perfume. Available 12 March 2018 at en.wikipedia.org/wiki/Perfume.
2. Perfume. Available 12 March 2018 at www.merriam-
webster.com/dictionary/perfume.
3. The Penguin English Dictionary. 2nd ed. Robert Allen, Consultant ed.
Penguin Books. 2003. England.
4. Shabby. Basic types of perfumes. Available 15 March 2018 at
stylecraze.com/articles/8-basic-types-of-perfumes/#gref.

BIBLICAL VERSES

Many Biblical references indicate the widespread use of

perfumes. The breath was purposely scented; clothing as well as the
body was perfumed; couches and beds were sprinkled with savory
scents; ointments were used in the last rites in honor of the dead.
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"Take also for yourself the finest of perfumes: of flowing myrrh five
hundred and of fragrant cinnamon half so much, two hundred and fifty, and
of fragrant calamus two hundred and fifty… " (Exodus 30:23).

"And you shall make of these a sacred anointing oil blended as by

the perfumer; it shall be a holy anointing oil" (Exodus 30:25).

“Take sweet spices, stacte, and onycha, and galbanum, sweet spices with
pure frankincense (of each shall there be a like weight. And make it a
perfume, a confection after the art of the apothecary, tempered together,
pure and holy" (Exodus 30:34-35).

"And he made the holy anointing oil and the pure, fragrant incense of
spices, the work of a perfumer" ( Exodus 37:29).

"I have perfumed my bed with myrrh, aloes, and cinnamon"

(Proverbs 7:17).

"Oil and perfume rejoice the heart… " (Proverbs 27:9) .

"And you wentest to the king with ointment and didst increase with
perfumes …" (Isaiah 57:9).

"Now when every maid's turn was come to go in to king Ahasverus, after
that she had been twelve months, according to the manner of the women,
(for so were the days of their purifications accomplished, to wit, six months
with oil of myrrh, and six months with perfumes, and with other ointments
for the purifying of the women" (Esther 2:12).

"… And they laid him in the resting place which was filled with spices of
various kinds blended by the perfumers' art…." (2 Chronicles 16:14) .

"He will also take your daughters for perfumers…" (1 Samuel 8:13).

Perfumes were used in religious worship, and for personal and

domestic enjoyment (1). Perfumes were mixed by persons skilled. In
the King James Version these are called "apothecaries" (raqqach).
The Revised Version (British and American) "perfumer" is probably a
more correct rendering, as the one who did the compounding was
not an apothecary in the same sense as is the person now so
designated (2).
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References
1. Perfume Available 15 March 2018 at
biblestudytools.com/dictionary/perfumes/.
2. Perfume. Available 16 March 2018 at
internationalstandardbible.com/P/perfume-perfumer.html.

HISTORY
As previously noted, in Biblical times the ancients were fond of
sweet perfumes of all kinds, and this characteristic is still especially
true of the people of Bible lands. Perfumed oils were rubbed on the
body and feet. At a feast in ancient Egypt a guest was anointed with
scented oils, and a sweet-smelling water lily was placed in his hand or
suspended on his forehead. In their religious worship the Egyptians
were lavish with their incense (1).

Egyptian scene depicting the preparation of Lily perfume.

Small pellets of dried mixed spices and resins or resinous woods

were burned in special censers. In the preparation of bodies for
burial, perfumed oils and spices were used (1).

Egyptian women enjoying perfume.

Ancient texts and archaeological excavations show the use of

perfumes in some of the earliest human civilizations (2).
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Etruscan perfume vase shaped like a female head,

2nd century BC.

Perfume was refined by the Romans, the Persians and the Arabs.
Although perfume and perfumery also existed in East Asia, much of
its fragrances were incense based. The basic ingredients and
methods of making perfumes were described by Pliny the Elder in his
Naturalis Historia (2).

MESOPOTAMIA
The world's first recorded chemist is a woman named Tapputi, a
perfume maker whose existence was first discovered on a 1200 BCE
Cuneiform tablet in Babylonian Mesopotamia (3). She held a
powerful role in the Mesopotamian government and religion, as the
overseer of the Mesopotamian Royal Palace. She developed
methods for "distillation, cold enfleurage, and tincture" (4) and other
scent extraction techniques that would lay the basis for perfume
making. She recorded her techniques and methods that were passed
on, with her most groundbreaking technique in using solvents (5).

Beauty Kit, Mesopotamian, 3000 B.C. Perfume Bottle.

Alabaster, Egypt.
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CYPRUS
To date, the oldest perfumery was discovered on the island of
Cyprus (6). Excavations in 2004-5 under the initiative of an Italian
archaeological team unearthed evidenced an enormous factory that
existed 4,000 years ago during the Bronze Age (7). This covered an
estimated surface area of over 4,000 m² indicating that perfume
manufacturing was on an industrial scale (8). The news of this
discovery was reported extensively through the world press and
many artifacts are on display in Rome (9).

Italian archaeologists have found the world's oldest perfumes on

Cyprus. The perfumes were scented with extracts of lavender, bay,
rosemary, pine or coriander and kept in tiny translucent alabaster.

ISLAMIC CULTURES
Islamic cultures contributed significantly to the development of
Western perfumery in two significant areas: perfecting the extraction
of fragrances through steam distillation and introducing new raw
materials. Both have influenced Western perfumery and scientific
developments, particularly chemistry (2).
With a rise of Islam, Muslims improved perfume production and
continued to use perfumes in daily life and in practicing religion.
They used musk, roses and amber, among other materials. As
traders, Islamic cultures such as the Arabs and Persians had wider
access to a wide array of spices, resins, herbs, precious woods, herbs
and animal fragrance materials such as ambergris and musk. In
addition to trading, many of the flowers and herbs used in perfumery
were cultivated by the Muslims — rose and jasmine were native to
the region, and many other plants (i.e. bitter orange and other citrus
trees, all of which imported from China and southeast Asia) could be
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successfully cultivated in the Middle East, and are to this day key
ingredients in perfumery (2).
In Islamic culture, perfume usage has been documented as far
back as the 6th century and its usage is considered a religious duty.
Muhammad said: The taking of a bath on Friday is compulsory for
every male Muslim who has attained the age of puberty and (also)
the cleaning of his teeth with Miswaak (type of twig used as a
toothbrush), and the using of perfume if it is available. (Recorded in
Sahih Bukhari). They often used to blend extracts with the cement of
which mosques were built. Such rituals gave incentives to scholars to
search and develop a cheaper way to produce incenses and in mass
production (10).
Many great discoveries originates from the region in 10th century,
the time when the still was invented, and as a consequence of which
the distill techniques considerably improved. Thanks to the hard
work of two talented Arabian chemists: Jābir ibn Hayyān (Geber, born
722, Iraq), and Al-Kindi (Alkindus, born 801, Iraq) who established the
perfume industry. Jabir developed many techniques, including
distillation, evaporation and filtration, which enabled the collection
of the odour of plants into a vapour that could be collected in the
form of water or oil (11).

Europe & the Islamic Mediterranean AD 700–1600

Gilded and enameled glass perfume sprinkler.

Al-Kindi, however, was the real founder of perfume industry as he

carried out extensive research and experiments in combining various
plants and other sources to produce a variety of scent products. He
elaborated a vast number of ‘recipes’ for a wide range of perfumes,
cosmetics and pharmaceuticals. His work in the laboratory is
reported by a witness who said: "I received the following description,
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or recipe, from Abu Yusuf Ya'qub b. Ishaq al-Kindi, and I saw him
making it and giving it an addition in my presence" (2).
The writer goes on in the same section to speak of the
preparation of a perfume called ghaliya, which contained musk,
amber and other ingredients; too long to quote here, but which
reveals a long list of technical names of drugs and apparatus. Al-Kindi
also wrote in the 9th century a book on perfumes which he named
‘Book of the Chemistry of Perfume and Distillations’. It contained
more than a hundred recipes for fragrant oils, salves, aromatic waters
and substitutes or imitations of costly drugs. The book also described
one hundred and seven methods and recipes for perfume-making,
and even the perfume making equipment, like the alembic, still bears
its Arabic name (12).
The Persian Muslim doctor and chemist Avicenna (also known as
Ibn Sina) introduced the process of extracting oils from flowers by
means of distillation, the procedure most commonly used today. He
first experimented with the rose. Until his discovery, liquid perfumes
were mixtures of oil and crushed herbs, or petals which made a
strong blend. Rose water was more delicate, and immediately
became popular. Both of the raw ingredients and distillation
technology significantly influenced western perfumery and scientific
developments, particularly chemistry (2).

INDIA
Perfume and perfumery also existed in Indus civilization (3300 BCE
- 1300 BCE). One of the earliest distillations of Ittar was mentioned in
the Hindu Ayurvedic text Charaka Samhita and Sushruta Samhita
(12). According to a 1975 report, an archeologist named Dr Paolo
Rovesti found a terra-cotta distillation apparatus in the Indus valley
together with oil containers made of the same material, and carbon
dating puts this at 3000 B.C., much earlier than it is conventionally
believed that distillation became practiced for the isolation of
essential oils. Terra cotta vessels with plugged orifices of woven
materials were used so that when fragrant plant materials were
covered with boiling water the vapors impregnated the material,
which was subsequently wrung out to isolate the oil (13).
The perfume references are part of a larger text called Brihat-
Samhita written by Varahamihira, an Indian astronomer,
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mathematician and astrologer who lived in the historic city of Ujjain.

He was one of the ‘nine jewels’ in the court of the Maharaja of
Malwa. The perfume portion mainly deals with the manufacture of
perfumes to benefit ‘royal personages and inmates of harems’. The
text is written as Sanskrit slokas with commentary by a 10th Century
Indian commentator Utpala (13).

An Indian Silver Filigree Rose-Water Sprinkler.

Pinteres.

In India perfumes and scented articles were in use from pre Vedic
and Vedic periods for religious practices, social customs, and
domestic rituals and later gradually became part and parcel of human
life. Perfumes were also used in cosmetics and beauty aids.
Medicinal values of many perfumes were well known to ancient
Indians and were used in both rituals and to treat diseases.
Medicated fumigation (dhupan) was an advanced method for
medicinal purposes. Medicated oils, collyriums, powders were
prepared from perfumes used externally in many diseases. Perfumes
were also anointed in various body parts (Anulepan). Chewing betel
leaves along with fragrant material like nutmeg, mace, etc.
(Tambulam) was used with a view to rendering mouth clean and
fragrant. Usage of scented oils to massage the body (Abhyanga)
which keeps the skin smooth, healthy and invigorating; Udvartanam,
massaging various body parts; Udgarshanam, scrubbing; Utsadanam
rubbing with scented powders etc., were some of the health
protective and disease eliminating procedures. Scented drugs and
perfumes enhance the quality, activity and pleasantness of these
processes (14).
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CHINA
It has a long history of the fragrance activities in the ancient
China. During the period of pre-Qin, it was mainly used in the
therapy and worship. Until the Three Kingdoms, the crowd using the
fragrance expanded from the royal to the literati and the general
officials. People applied the spices to incense clothes, purify rooms,
prevent and treat epidemic diseases in daily. In the worship, the
spices were dedicated to Gods and other fairies. The fragrance was
developed quickly during the period from Wei Dynasty to South and
North Dynasties. People had more experiences of spices used as
medicines, the formula of spices were used more widely. Then,
during the period from Sui Dynasty to Song Dynasty, the fragrance
activities climbed to the peak. The fragrance activities were
institutionalized, when nobility matched their spices each other. The
Literati made spice products and enjoyed the fragrance activities.
Doctors knew more than before in the application experiences and
species of spices. In the times of Yuan, Ming and Qing Dynasty, the
fragrance activities spread among the public. The spices appeared in
each side of the daily life of nobility, when natural fruits appeared in
the fragrance activities. External therapy with spices appeared in the
clinical. In addition to prevention and therapy, spices should be used
in the embalming. After a long period, the fragrance activities had
gradually developed into a kind of culture (15).
The ancient Chinese relationship with scent didn't really focus on
the body: rather than wearing perfume, ancient Chinese culture
utilized scent by burning incense and fragrant material in special
spaces. Histories of the use of scent in Chinese society tend to
emphasize that perfumes were not originally considered a cosmetic
there; rather, they were used for disinfection and purity, as it was
believed that they could eliminate disease from rooms. While
scented flowers were a part of traditional gardens, and mandarin
oranges were once used by noblewomen to scent their hands, it
seems that for centuries, wearing perfumes on his/her body was not
necessarily the "in thing" in China. But even though there is a myth
today that there was no perfume used on bodies in ancient China, it
is nonsense. According to Chinese chemistry historians, the period
between the Sui and the Song dynasties was rife with personal
perfumes, with nobles competing for the best scents and importing
ingredients via the Silk Road. By the Qing dynasty (1644-1912), the
 11

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emperor seems to have carried a "perfume pouch" year-round, an

adaptation of the traditional pocket pouch that brought good luck —
except that his was stuffed with fragrant herbs. The big difference
between this and other perfume traditions, though? A lot of Chinese
perfume ingredients were also used for many other purposes, like
food and medicine (16).

Chinese Perfume Bottles.

Pinterest.

EUROPE
Eventually perfume arrived to European courts through Al-
Andalus in the west, and on the other side, with the crusaders in the
east. For instance, eggs and floral perfumes were brought to Europe
in the 11th and 12th centuries from Arabia, by returning crusaders,
through trade with the Islamic world. Those who traded for these
were most often also involved in trade for spices and dyestuffs.
There are records of the Pepperers Guild of London, going back to
1179; which show them trading with Muslims in spices, perfume
ingredients and dyes (17). Catharina de Medici initiated the perfume
industry in Europe when she left Italy in the 16th century to marry
the French crown prince (10).

Perfumery in Western Europe.

Bespoke Unit.
 10

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Perfumery came to Europe as early as the 14th century due

partially to Arabic influences and knowledge. But it was the
Hungarians who ultimately introduced the first modern perfume.
The first modern perfume, made of scented oils blended in an alcohol
solution, was made in 1370 at the command of Queen Elizabeth of
Hungary and was known throughout Europe as Hungary Water. The
art of perfumery prospered in Renaissance Italy, and in the 16th
century, Italian refinements were taken to France by Catherine de'
Medici's personal perfumer, Rene le Florentin. His laboratory was
connected with her apartments by a secret passageway, so that no
formulas could be stolen en route (2).
France quickly became the European center of perfume and
cosmetic manufacture. Cultivation of flowers for their perfume
essence, which had begun in the 14th century, grew into a major
industry in the south of France mainly in Grasse and now is
considered the world capital of perfume. During the Renaissance
period, perfumes were used primarily by royalty and the wealthy to
mask body odors resulting from the sanitary practices of the day.
Partly due to this patronage, the western perfumery industry was
created. Perfume enjoyed huge success during the 17th century.
Perfumed gloves became popular in France and in 1656 the guild of
glove and perfume-makers was established. Perfumers are known to
create poisons; for instance, a French duchess was murdered when a
perfume/poison was rubbed into her gloves and was slowly absorbed
into her skin (2).

An original bottle of Fougère Royaleby Houbigant. Created by Paul

Parquetin, 1884, it is one of the most important modern perfumes and
inspired the eponymous Fougère class of fragrances.

Perfume came into its own when Louis XV came to the throne in
the 18th century. His court was called "la cour parfumée" (the
 11

L. Ben-Nun Perfumes

perfumed court). Madame de Pompadour ordered generous

supplies of perfume, and King Louis demanded a different fragrance
for his apartment every day. The court of Louis XIV was even named
due to the scents which were applied daily not only to the skin but
also to clothing, fans and furniture. Perfume substituted for soap
and water. The use of perfume in France grew steadily. By the 18th
century, aromatic plants were being grown in the Grasse region of
France to provide the growing perfume industry with raw materials.
Even today, France remains the center of the European perfume
design and trade (2).

19th Century Louis XV Parquetry Perfume Casket,

Four Bottles.

After Napoleon came to power, exorbitant expenditures for

perfume continued. Two quarts of violet cologne were delivered to
him each week, and he used sixty bottles of double extract of jasmine
every month. Josephine had stronger perfume preferences. She was
partial to musk, and she used so much that sixty years after her death
the scent still lingered in her boudoir (2).
Perfume use peaked in England during the reigns of Henry VIII
(reigned 1509-1547) and Queen Elizabeth I (reigned 1558-1603). The
sharpness of her nose was equaled only by the slyness of her tongue.
Ladies of the day took great pride in creating delightful fragrances
and they displayed their skill in mixing scents (2).
As with industry and the arts, perfume underwent profound
change in the 19th century. Changing tastes and the development of
modern chemistry laid the foundations of modern perfumery as
alchemy gave way to chemistry (2).
 12

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RUSSIA
Perfume manufacture in Russia grew after 1861 and became
globally significant by the early 20th century (18). The production of
perfume in the Soviet Union became a part of the planned economy
in the 1930s (19).]

Russian 19th century porcelain perfume.

References
1. Perfume. Available 10 March 2018 at biblehub.com/topical/p/perfume.htm.
2. History of Perfume. Available 14 March 2018 at
en.wikipedia.org/wiki/Perfume.
3. Strathern, Paul. Mendeleyev's Dream — The Quest For the Elements. New
York: Berkley Books. 2000. ISBN 0-425-18467-6.
4. Alic M. Hypatia's heritage, a history of women in science from antiquity
through the nineteenth century. Boston, MA: Beacon Press. 1987, pp. 22.
5. Kass-Simon G, Farnes P, Nash D (eds.). Women of science: righting the
record (First Midland Book ed.). Bloomington, Ind.: Indiana Univ. Press. 1999, p.
301.
6. Theodoulou M. Archaeological dig sniffs out world's oldest perfumery. The
Scotsman. Available 14 March 2018 scotsman.com/news.
7. Morgan T. Bronze Age perfume 'discovered. Available 15 March 2018 at
http://news.bbc.co.uk/2/hi/europe/4364469.stm.
8. Moore Malcolm. Eau de BC: the oldest perfume in the world. 2007.
Available 16 March 2018 at
telegraph.co.uk/news/?xml=/news/2007/03/21/wperfume21.xml.
9. Roach John. Oldest Perfumes Found on "Aphrodite's Island". National
Geographic News. Oldest perfumes. 2007. Available 10 March 2018 at
news.nationalgeographic. com/news/2007/03/070329-oldest-perfumes. html?
Source=rss.
10. Wiedemann M Plessner. "AL-ANBĪḲ". The Encyclopaedia of Islam, 1 (2nd
ed.), Brill. 1986, p. 486 a.
11. Henry George Liddell, Robert Scott (eds.). "ἄμβιξ". Greek-English Lexicon
(8th ed.), Harper & Brothers, 1897, p. 73.
12. Marcellin Berthelot. Introduction à l'étude de la chimie des anciens et du
moyen âge, Steinheil. 1889, p. 164.
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L. Ben-Nun Perfumes

13. Sharma AK, Wahad S, Śrīvāstava R. Agriculture Diversification: Problems

and Perspectives. I. K. International Pvt Ltd. 2010, p. 140.
14. Prasad GP, Pratap GP, Neelima M, Satyanrayanashastry VP. Historical
perspective on the usage of perfumes and scented Articles in ancient Indian
literatures. Anc Sci Life. 2008;28(2):33-9.
15. Ding JY, Jin ZJ. The origin and development of fragrance activity in Chinese
ancient times. Zhonghua Yi Shi Za Zhi. 2010;40(3):131-6.
16. The Strange History of Perfume, From Ancient Roman Foot Fragrance to
Napoleon's Cologne. Available 12 March 2018 at bustle.com/articles/101182-the-
strange-history-of-perfume-from-ancient-roman-foot-fragrance-to-napoleons-
cologne.
17. Tracy P. So, What's All the Sniff About?: An In-Depth Plea for Sanity and
Equal Rights for Your Sense of Smell, Our Most Neglected and Endangered Sense.
So What's all the Sniff about. 2000, p. 46. ISBN 9780968707609.
18. Geoffrey J. Beauty Imagined: A History of the Global Beauty Industry. OUP
Oxford. 2010. ISBN 9780191609619.
19. Reid Susan E. Gender and the Destalinisation of Consumer Taste in the
Soviet Union under Khrushchev. In Martens L, Casey E. Gender and Consumption:
Domestic Cultures and the Commercialisation of Everyday Life. Ashgate Publishing,
Ltd. 2012. ISBN 9781409490845.

SMELL/BODY ODOR
Olfaction is often referred to as a multidimensional sense. It is
multidimensional in that approximately 1,000 different receptor
types, each tuned to particular odor aspects, together contribute to
the olfactory percept. In humans, however, this percept is nearly
unidimensional. Humans can detect and discriminate countless
odorants, but can identify few by name. The one thing humans can
and do invariably say about an odor is whether it is pleasant or not.
This hedonic determination is the key function of olfaction. Thus, the
boundaries of an odor object are determined by its pleasantness,
which unlike something material and more like an emotion remains
poorly delineated with words (1).
The main problem with sensory processing is the difficulty in
relating sensory input to physiological responses and perception.
This is especially problematic at higher levels of processing, where
complex cues elicit highly specific responses. In olfaction, this
relationship is particularly obfuscated by the difficulty of
characterizing stimulus statistics and perception. The core questions
in olfaction are hence the so-called stimulus problem, which refers to
the understanding of the stimulus, and the structure-activity and
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L. Ben-Nun Perfumes

structure-odor relationships, which refer to the molecular basis of

smell. It is widely accepted that the recognition of odorants by
receptors is governed by the detection of physico-chemical
properties and that the physical space is highly complex. Not
surprisingly, ideas differ about how odor stimuli should be classified
and about the very nature of information that the brain extracts from
odors. Even though there are many measures for smell, there is
none that accurately describes all aspects of it. An approach to
olfactory function where information processing is emphasized could
contribute to a high degree to our understanding of smell as a
perceptual phenomenon emerging from neural computations.
Combined analysis of the stimulus, biology, physiology, and behavior
and perception can provide new insights into olfactory function (2).
The origins of the sense of smell lie in the perception of
environmental molecules and go back to unicellular organisms such
as bacteria. Odors transmit a multitude of information about the
chemical composition of our environment. The sense of smell helps
people and animals with orientation in space, warns of potential
threats, influences the choice of sexual partners, and regulates food
intake and influences feelings and social behavior in general. The
perception of odors begins in sensory neurons residing in the
olfactory epithelium that express G protein-coupled receptors, the
so-called olfactory receptors. The binding of odor molecules to
olfactory receptors initiates a signal transduction cascade that
converts olfactory stimuli into electrical signals. These signals are
then transmitted to the olfactory bulb, the first relay center in the
olfactory pathway, via the axons of the sensory neurons. The
olfactory information is processed in the bulb and then transferred to
higher olfactory centers via axons of mitral cells, the bulbar
projection neurons (3).
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Previous research suggests that artificial fragrances may be

chosen to complement or enhance an individual's body odor, rather
than simply masking it, and that this may create an odor blend with
an emergent quality that is perceptually distinguishable from body
odor or fragrance alone. From this, it can be predicted that a new
emergent odor might be more easily identified than an individual's
body odor in isolation. A triangle test paradigm was used to assess
whether fragrance affects people's ability to distinguish between
individual odors. Six male and six female donors provided axillary
odor samples in three conditions (without fragrance, wearing their
own fragrance, and wearing an assigned fragrance). In total, 296
female and 131 male participants selected the odd one from three
odor samples (two from one donor, one from another; both of the
same sex). Participants could discriminate between the odors at
above chance levels in all three odor conditions. Olfactory
identification ability (measured using Sniffin' Sticks) positively
predicted discrimination performance, and sex differences in
performance were also observed, with female raters being correct
more often than men. Success rates were higher for odors of male
donors. Additionally, while performance was above chance in all
conditions, individual odor discrimination varied across the three
conditions. Discrimination rate was significantly higher in the "no
fragrance" condition than either of the fragranced conditions.
Importantly, however, discrimination rate was significantly higher in
the "own fragrance" condition than the "assigned fragrance"
condition, suggesting that naturally occurring variance in body odor is
more preserved when blended with fragrances that people choose
for themselves, compared with other fragrances. The data are
consistent with the idea that fragrance choices are influenced by
fragrance interactions with an individual's own body odor (4).
People can accurately assess various personality traits of others
based on body odor alone. Previous studies have shown that
correlations between odor ratings and self-assessed personality
dimensions are evident for assessments of neuroticism and
dominance. Here, differences were tested between assessments
based on natural body odor alone, without the use of cosmetics and
assessments based on the body odor of people who were allowed to
use cosmetics following their daily routine. Sixty-seven observers
assessed samples of odors from 113 odor donors (each odor donor
 16

L. Ben-Nun Perfumes

provided two samples - one with and one without cosmetic use); the
donors provided their personality ratings, and the raters judged
personality characteristics of the donors based on the provided odor
samples. Correlations between observers' ratings and self-rated
neuroticism were stronger when raters assessed body odor in the
natural body odor condition (natural body odor condition; r s = 0.20)
than in the cosmetics use condition (body odor + cosmetics
condition; r s = 0.15). Ratings of dominance significantly predicted
self-assessed dominance in both conditions (r s = 0.34 for natural
body odor and r s = 0.21 for body odor + cosmetics), whereas ratings
of extraversion did not predict self-assessed extraversion in either
condition. In addition, ratings of body odor attractiveness and
pleasantness were significantly lower in natural body odor condition
than in body odor + cosmetics condition, although the intensity of
donors' body odors was similar under both conditions. The findings
suggest that although olfaction seems to contribute to accurate first
impression judgments of certain personality traits, cosmetic use can
affect assessments of others based on body odor (5).
Clinical toxicologists perform risk assessments and clinical
evaluations for patients with potential exposure to airborne toxicants
in which the patient's self-reported perception of odor may be the
only indicator that an exposure may have taken place. The factors
that may affect the human ability to perceive chemical odors and
relate those odors to specific chemical exposures were reviewed.
The medical literature, from 1950 through 2012, was searched using
the OVID database and the PUBMED database. The searches
returned 238 articles, of which 113 involved human studies and were
published in the English language. Of these 113 articles, 40 articles
discussed odor issues and thus were chosen as specifically relevant to
the topic. Bibliographies of all articles were also searched for other
relevant references and six additional articles were found, making a
total of 46. Genetic/population: Ethnic background is associated with
widely differing odor detection abilities and thresholds. A significant
genetic influence for the ability to smell and perceive odor has been
reported. Gender: Women are superior to men in their ability to
identify odors. Increasing age is correlated with higher odor
detection thresholds. Medical conditions: A variety of medical
conditions have been associated with deficits in olfaction, including
diseases of the nose and sinuses, multiple sclerosis, and
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L. Ben-Nun Perfumes

schizophrenia. Alcoholism and smoking: Abuse of alcohol results in

impaired olfactory sense, and smoking tobacco products alter odor
detection threshold in a dose-related manner. Occupational and
environmental factors: repeated inhalation of any chemical results in
olfactory fatigue over relatively short time frames that leads to a
decreased ability to accurately detect and identify an odor. Recent
exposure to relatively high concentrations of a chemical affects
sensitivity to that particular odorant, altering subsequent detection
thresholds by up to three orders of magnitude. Applicability of
proposed odor thresholds: humans are only able to identify three to
four components of complex olfactory mixtures and the odorants
present in the mixture affect which individual components are
detected. Odorants present in suprathreshold concentrations in a
mixture may effectively mask the presence of odorants present in
perithreshold concentrations. Self-rating of olfactory function may
not correlate with actual olfactory ability. It is even more difficult to
accurately determine intensity of an odor in a quantifiable way. For
example, under conditions of constant stimulation with hydrogen
sulfide, perceptual intensity decreased exponentially with time of
stimulation. Concomitant visual stimulation also affects odor
intensity. Some chemicals, such as hydrogen sulfide, may induce
reactions in humans related solely to their odor, even when they are
present in concentrations substantially lower than those levels
usually associated with the development of adverse clinical effects.
There is a wealth of literature suggesting that the intensity of
perceived odor, the degree of irritation, and the reported health
effects of exposure to an odorant chemical are affected by
psychological state and bias. Multiple theories have been proposed
to explain the cognitive basis for perceived illness in association with
the perception of odor. The concept of odor has been reported to be
intrinsically and cognitively associated with illness rather than with
health. Assign negative bias to an odor prior to an exposure results in
the reporting of significantly more health-related symptoms
following exposure. This suggests that those symptoms are not
mediated by the odor directly, but rather by an individual's cognitive
associations between odor and health. In conclusion, attempts to
verify exposure intensity based on the report of a perceived odor is
unreliable and has no useful application in legitimate exposure
assessment paradigms. Detection of an odor does not imply a
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medically significant exposure to a toxicant and, due to subject bias

and the difficulty of detecting individual odorants in mixtures may
not constitute an exposure to the purported substance (6).
Infant body odor is subjectively pleasant to parents and activates
reward areas in the brain. Hence, body odor perception might
contribute to parental bonding. However, it is unknown whether the
perceived pleasantness of children's body odor varies over the course
of a child's development. Two hundred and thirty-five parents (M =
36.9 years, SD = 7.3) were asked to assess the personal odor
pleasantness of their children (n=367; M = 9.3 years, SD = 6.4). Odor
pleasantness was found to decrease as a function of children's age.
Neither sex of the parent nor sex of the child contributed significantly
to this effect. In conclusion, the effect of age-related changes on
personal odor pleasantness reflects olfactory modulation of parental-
child relationships. In conclusion, perception of young children's
personal odor as pleasant may contribute to bonding and thereby
caretaking, which is needed to a lesser degree after puberty than
before (7).
A research is reviewed regarding the relationship between odor
perception or irritation and setting an occupational exposure limit
(OEL). Special focus is directed at those settings where a small
fraction of persons report unacceptable responses to concentrations
well below the OEL. The published literature was evaluated on the
topic of irritation and olfactory response to exposure to industrial
chemicals. More than a dozen researchers have been active in this
area over the past 10 years. For some chemicals, even when one
maintains airborne concentrations below a particular OEL, the level
of exposure may not be adequate to prevent all persons from
reporting an appreciable adverse response. In some cases, worker's
pre-existing belief systems about the source of an odor may be
sufficient to notice that they have not been exposed to any
detectable concentration. In addition, detection of odors by workers
may tap into the person's aversion to odors, in general. In both
situations, it is often necessary to address these specific issues
through risk communication and dealing directly with risk perception.
In conclusion, for practical reasons, the current objective of
organizations charged with setting OELs for chemicals is to identify
concentrations that do not cause irritation or widespread reports of
 21

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unpleasant sensory stimulation in the vast majority of workers (e.g.,

about 80-95%) (8).
Emotions are characterized by synchronized changes in several
components of an organism. Among them, physiological variations
provide energy support for the expression of approach/avoid action
tendencies induced by relevant stimuli, while self-reported subjective
pleasantness feelings integrate all other emotional components and
are plastic. Consequently, emotional responses evoked by odors
should be highly differentiated when they are linked to different
functions of olfaction (e.g., avoiding environmental hazards). As this
differentiation has been observed for contrasted odors (very pleasant
or unpleasant), it has been questioned whether subjective and
physiological emotional response indicators could still disentangle
subtle affective variations when no clear functional distinction is
made (mildly pleasant or unpleasant fragrances). Here, the
sensitivity of behavioral and physiological [respiration, skin
conductance, facial electromyography (EMG), and heart rate]
indicators were compared in differentiating odor-elicited emotions in
two situations: when a wide range of odor families was presented
(e.g., fruity, animal), covering different functional meanings; or in
response to a restricted range of products in one particular family
(fragrances). Results show clear differences in physiological
indicators to odors that display a wide range of reported
pleasantness, but these differences almost entirely vanish when
fragrances are used even though their subjective pleasantness still
differed. Taken together, these results provide valuable information
concerning the ability of classic verbal and psychophysiological
measures to investigate subtle differences in emotional reactions to a
restricted range of similar olfactory stimuli (9).
Sensory irritation levels was assessed from isopropanol (IPA)
unconfounded by subjective evaluations of odor for comparison
against the recommended exposure limits (400 ppm threshold limit
value (TLV)); American Conference of Governmental Industrial
Hygienists). The lateralization method was used to assess intra-nasal
irritation thresholds for IPA, while odor detection thresholds were
also measured. Thresholds for 1-butanol and phenyl ethyl alcohol
(PEA) were obtained as positive and negative irritant controls. To
compare potency and hedonic characteristics, subjects provided
subjective ratings of odor, irritation and annoyance intensity for
 20

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three concentrations of each chemical. Workers occupationally

exposed to IPA (n=26) were compared with previously unexposed
controls (n=26). The (geometric) mean odor detection threshold for
IPA was slightly higher among exposed workers than controls (39
ppm vs. 11 ppm). Lateralization thresholds measuring intra-nasal
irritation were elevated when compared with controls (6,083 ppm in
exposed workers vs. 3,361 ppm in naïve controls), with a significantly
higher proportion of phlebotomists being unable to lateralize the
maximum concentration regarded as safe, than controls.
Calculations of the 6th percentile for lateralization thresholds
revealed that 95% of the sample did not experience sensory irritation
below 512 ppm. Thus, while odor detection thresholds were well
below the current recommended exposure limits, the irritation
thresholds were well above these values. The odor, irritation and
annoyance from IPA was perceived, on average, as between weak
and almost strong, from lowest to highest concentration. In
conclusion, the results indicate that current exposure guidelines
would be adequately protective of the acute adverse effect of nasal
sensory irritation, as operationally defined by the intra-nasal
lateralization threshold. Exposures to higher concentrations should
perhaps be evaluated on the basis of existing knowledge about
systemic, rather than local (e.g., irritation), toxic effects. IPA appears
to be a weak sensory irritant and occupational exposure to IPA
appears to elicit small changes in sensitivity that do not generalize to
other odorants (e.g., PEA and 1-butanol) and are likely to be
reversible (10).
The subjectivity of irritancy judgments can bias attempts to
establish exposure guidelines that protect individuals from the
sensory irritation produced by volatile chemicals. At low to moderate
chemical concentrations, naive and occupationally exposed
individuals often show considerable variation in the reported levels
of perceived irritation. Such variation could result from differences in
exposure history, differences in the perceived odor of a chemical, or
differences in generalized response tendencies to report irritation, or
response bias. Thus, experimental evaluation of sensory irritancy
must dissociate sensory irritation from response bias. To this end,
judgments of perceived irritation from 800 ppm acetone were
obtained from acetone-exposed workers and age- and gender-
matched naive controls. To assess the role of response bias during
 21

L. Ben-Nun Perfumes

exposure to odorants, subjects were also exposed to PEA, an odorant

that does not produce sensory irritation. Following exposure,
subjects completed a subjective symptom survey that included
symptoms that have been associated with long-term solvent
exposures and symptoms that have not. Acetone-exposed workers
and naive controls reported large differences in the perceived
intensity of odor and irritation from acetone, yet no differences in
the perception of PEA. However, for both groups, the most
significant factors mediating reported irritancy and health symptoms
from acetone were the perceived intensity of its odor and an
individual's bias to report irritation from PEA. The perception of odor
intensity and degree of response bias will differ between and within
groups of exposed and naive individuals; hence, an assessment of the
influence of these factors in experimental and workplace studies of
chemical irritancy is warranted (11).

ASSESSMENT: olfaction is often referred to as a multidimensional

sense. It is multidimensional in that approximately 1,000 different
receptor types, each tuned to particular odor aspects, together
contribute to the olfactory percept. In humans, however, this
percept is nearly unidimensional.
The origins of the sense of smell lie in the perception of
environmental molecules and go back to unicellular organisms such
as bacteria.
Artificial fragrances may be chosen to complement or enhance an
individual's body odor, rather than simply masking it, and this may
create an odor blend with an emergent quality that is perceptually
distinguishable from body odor or fragrance alone.
Fragrance choices are influenced by fragrance interactions with an
individual's own body odor.
Sensitivity of physiological emotional measures to odors depends
on the product and the pleasantness ranges used. Emotional
responses evoked by odors should be highly differentiated when they
are linked to different functions of olfaction (e.g., avoiding
environmental hazards).

References
1. Yeshurun Y, Sobel N. An odor is not worth a thousand words: from
multidimensional odors to unidimensional odor objects. Annu Rev Psychol. 2010;
61:219-41, C1-5.
 22

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2. Auffarth B. Understanding smell - the olfactory stimulus problem. Neurosci

Biobehav Rev. 2013;37(8):1667-79.
3. Manzini I, Frasnelli J, Croy I. How we smell and what it means to us: basic
principles of the sense of smell. HNO. 2014;62(12):846-52.
4. Allen C, Havlíček J, Roberts SC. Effect of fragrance use on discrimination of
individual body odor. Front Psychol. 2015 Aug 7;6:1115.
5. Sorokowska A, Sorokowski P, Havlíček J. Body odor based personality
judgments: the effect of fragranced cosmetics. Front Psychol. 2016 Apr 18;7:530.
6. Greenberg MI, Curtis JA, Vearrier D. The perception of odor is not a
surrogate marker for chemical exposure: a review of factors influencing human
odor perception. Clin Toxicol (Phila). 2013;51(2): 70-6.
7. Croy I, Frackowiak T, Hummel T, Sorokowska A. Babies smell wonderful to
their parents, teenagers do not: an exploratory questionnaire study on children's
age and personal odor ratings in a Polish sample. Chemosens Percept. 2017;
10(3):81-7.
8. Paustenbach DJ, Gaffney SH. The role of odor and irritation, as well as risk
perception, in the setting of occupational exposure limits. Int Arch Occup Environ
Health. 2006;79(4):339-42.
9. Pichon AM, Coppin G, Cayeux I, et al. Sensitivity of physiological emotional
measures to odors depends on the product and the pleasantness ranges used.
Front Psychol. 2015 Dec 1;6:1821.
10. Smeets M, Dalton P. Perceived odor and irritation of isopropanol: a
comparison between naïve controls and occupationally exposed workers. Int Arch
Occup Environ Health. 2002;75(8):541-8.
11. Dalton P, Wysocki CJ, Brody MJ, Lawley HJ. Perceived odor, irritation, and
health symptoms following short-term exposure to acetone. Am J Ind Med. 1997;
31(5):558-69.

PERFUMER
A perfumer is a term used for an expert on creating perfume
compositions, sometimes referred to affectionately as a Nose
(French: le nez) due to their fine sense of smell and skill in producing
olfactory compositions. The perfumer is effectively an artist (1) who
is trained in depth on the concepts of fragrance aesthetics and who is
capable of conveying abstract concepts and moods with fragrance
compositions (1).
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Perfumer filling a perfume vial from an aryballos, fragment.

Ancient History Painting – Etruscan.

At the most rudimentary level, a perfumer must have a keen

knowledge of a large variety of fragrance ingredients and their
smells, and be able to distinguish each of the fragrance ingredients
whether alone or in combination with other fragrances. As well, they
must know how each ingredient reveals itself through time with
other ingredients. The job of the perfumer is very similar to that of
flavourists, who compose smells and flavourants for many
commercial food products. The practice of perfume-making has
recently attracted academic interest among major research funding
agencies (2).

Potpourri. Edwin Austin Abbey. 1899.

References
1. Glen O. Brechbill. The Perfumers - An Index to the Aromatic Artists.
Available 10 March 2018 at Perfumerbook.com.
2. The SNSF P3 Grant Search Database. Available 12 March 2018 at
p3.snf.ch/Project-147133.
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PERFUME SELECTION

People tend to choose perfumes to complement their body odor.

As kin share some body odor qualities, their ability to select
complementary perfumes for relatives might be higher compared
with selection for nonrelatives. Selection of a perfume was
compared for a target man by himself and by either a familiar but
unrelated individual (girlfriend; Study 1) or a relative (sister; Study 2).
Target men applied the two perfumes (own or other's choice) to their
axillae and then wore cotton pads for 12 hours. Collected perfume-
body odor blends and perfumes alone were assessed by rater panels.
In Study 1, the blends were rated as nominally more pleasant when
body odors were mixed with the perfumes selected by girlfriends
compared with those selected by target men themselves. In Study 2,
body odors mixed with perfumes selected by sisters were rated
significantly more attractive than those mixed with perfumes
selected by target men. Insignificant differences were found for
attractiveness and pleasantness ratings when perfumes were rated
alone, suggesting that it was the resulting blends that were uniquely
different. The results indicate that sisters might be particularly tuned
to select suitable perfumes for their siblings (1).

Scent communication in man is undoubtedly of importance,

although it is unconscious, rather than active, as compared to
subhuman primates. Besides human sexual life it also affects a
number of further characteristics of human life and its infrastructure
including the mother-child relationship, creation of the odor basis of
the family with the possibility to identify the family members solely
by their odor as well as other parameters investigated thus far.
Pheromones have effect upon the selection of a suitable partner of
the opposite sex (or of the same sex in homosexual partners). The
formation of specifically significant responses during communication
between the two sexes, first of all in sexual life and its
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manifestations, may also be influenced by pheromone-based

perfumes or classical cosmetic perfumes, as far as they are selected
and used appropriately. The situation is much easier if the partners
are of the olfactory type where for both partners the mutual
olfactory parameters are the most attractive for their sexual life and
its parameters, which significantly contributes to the quality of their
overall coexistence (2).

Cross-culturally, fragrances are used to modulate body odor, but

the psychology of fragrance choice has been largely overlooked. The
prevalent view is that fragrances mask an individual's body odor and
improve its pleasantness. In two experiments, positive effects of
perfume on body odor perception were found. Importantly,
however, this was modulated by significant interactions with
individual odor donors. Fragrances thus appear to interact with body
odor, creating an individually-specific odor mixture. In a third
experiment, the odor mixture of an individual's body odor and their
preferred perfume was perceived as more pleasant than a blend of
the same body odor with a randomly-allocated perfume, even when
there was no difference in pleasantness between the perfumes. This
indicates that fragrance use extends beyond simple masking effects
and that people choose perfumes that interact well with their own
odor. The results provide an explanation for the highly individual
nature of perfume choice (3).

Vintage atomizer perfume bottle.

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ASSESSMENT: there is effect of biological relatedness on perfume

selection for others.
Cosmetic perfumes vs. human pheromones of the human female
and male are signaling and perform context of their sexual behavior.
Pheromones have effect upon the selection of a suitable partner of
the opposite sex or of the same sex in homosexual partners.
The formation of specifically significant responses during
communication between the two sexes, first of all in sexual life and
its manifestations, may also be influenced by pheromone-based
perfumes or classical cosmetic perfumes, as far as they are selected
and used appropriately.
Fragrances mask an individual's body odor and improve its
pleasantness. Fragrance use extends simple masking effects and
people choose perfumes that interact well with their own odor.

References
1. Sobotková M, Fialová J, Roberts SC, Havlíček J. Effect of biological
relatedness on perfume selection for others: preliminary evidence. Perception.
2017;46(3-4):498-515.
2. Zaviacic M, Sisovsky V, Zaviacic T. Cosmetic perfumes vs. human
pheromones (natural chemical scents) of the human female and male in signalling
and performing context of their sexual behaviour. Bratisl Lek Listy.
2009;110(8):472-5.
3. Lenochová P, Vohnoutová P, Roberts SC, et al. Psychology of fragrance use:
perception of individual odor and perfume blends reveals a mechanism for
idiosyncratic effects on fragrance choice. PLoS One. 2012;7(3):e33810.

TYPES
Types of perfumes include: Floral, Citrus, Woody, Oriental, Fruity,
Green, Oceanic, and Spicy (1):

FLORAL
Floral fragrances cover the largest category of the different types
of perfumes which draw inspiration from different sweet smelling
flowers like roses, jasmine, orange blossoms, gardenias and
carnations amongst others.
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cc licensed ( BY NC SA ) flickr photo

shared by Halil Gokdal

Floral fragrances are romantic and sweet smelling. These usually

have a single note or a blend of different notes from different
flowers. Floral fragrances are feminine in nature and are classic
choices for those who want a perfume with feminine touch.

CITRUS
Citrus-based perfumes have the essence of citrus to offer a tangy
feel. These perfumes are lively and are perfect for person with a
bubbly nature. Citrus fragrances are derived from lime, lemon,
tangerine and mandarin; and some can feature real sharp tangy
notes. Citrus fragrances also tend to give a naturally refreshing
feeling and are perfect for use during the daytime. These blend well
and give women a very soft fragrance which can be worn with ease.

cc licensed ( BY SA ) flickr photo

shared by Shaun Dunphy.

WOODY
A combination of wood and moss is the main theme of these
Woody fragrances, and are most commonly referred as chypre
fragrances. The predominant use of oak moss, citrus, patchouli,
bergamont as well as sweet earthy aromas help in creating a very
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soothing perfume. Chypre fragrances usually refer to fragrances for

female category and sometimes the unisex, but are not for the male
category. There is a strong and classical appeal in these chypre
fragrances as these are most frequently used by corporate workers.

cc licensed ( BY ) flickr photo

shared by Nicholas A. Tonelli.

ORIENTAL
Oriental perfumes are a mix of earthy and musky fragrances.
Ingredients like amber, musk, and animalistic base scents are often
seen in Oriental perfumes.

These are claimed to be ideal when one wants to attract attention

or seduce that very special person. It is ideal for wearing on a special
date or a romantic night out.

FRUITY
Fruity smells are pleasant and largely popular due to their
sweetness. They have a blend of spicy and fruity notes which help
make these ideal for usual dates and romantic outings. These include
smells like apple, berry, mango, peach and other juicy fruits or
possibly the essence of these fruits.
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cc licensed (BY SA ) flickr photo

shared by David.

GREEN
Green fragrances are good choices for daytime casual events, as
they offer scents of fresh leaves and newly mown grass. Green
fragrances are sporty and in most cases tend to be unisex perfumes.

cc licensed ( BY ) flickr photo

shared by Roberto Verzo.

These perfumes are considerately mild and should be worn on

casual events or occasions.

OCEANIC
Oceanic fragrances are a relatively newer type of perfumes
containing synthetic aromas to resemble smells of mountain air,
clean linen, etc.
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Oceanic fragrances are claimed to be very good choices

for job interviews and official events.

SPICY
Spicy fragrances have their own alluring scents and are luxurious
in an old fashioned sense. These fragrances are a huge hit for casual
occasions and brunches.

cc licensed ( BY SA ) flickr photo

shared by Bala Sivakumar.

The fragrances in the kitchen smell like cinnamon, ginger,

cardamom, cloves, and pepper.

Reference
1. Shabby. Basic types of perfumes. Available 15 March 2018 at
stylecraze.com/articles/8-basic-types-of-perfumes/#gref.

COMPOSITION OF PERFUMES
What does it mean to create fragrances with materials from
chemistry and/or from nature? How are they used to display their
characteristic differences, their own personality? Is it easier to create
with synthetic raw materials or with essential oils? This review
explains why a perfume formulation corresponds in fact to a
conversation, interplay between synthetic and natural perfumery
materials. A synthetic raw material carries single information, and
usually is linear. Its smell is uniform, clear, and faithful. Natural raw
materials, on the contrary, provide a strong, complex and generous
image. While a synthetic material can be seen as a single word, a
natural one such as rose oil could be compared to chatting: cold,
warm, sticky, heavy, transparent, pepper, green, metallic, smooth,
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watery, and fruity. Yet, if a very small amount of the natural material
is used, nothing happens, the fragrance will not change. However, if
a large amount is used, the rose oil will swallow up everything else.
The fragrance will smell of nothing else except rose! To formulate a
perfume is not to create a culinary recipe, with only dosing the
ingredients in well-balanced amounts. To formulate rather means to
flexibly knit materials together with a lively stitch, meeting or
repelling each other, building a pleasant form, this is neither fixed,
nor solid, nor rigid. A fragrance has an overall structure, which
ranges from a clear sound, made up of stable, unique, and linear
items to a background chat, comfortable and reassuring. But that
does, of course, not mean that there is only one way of creating a
fragrance (1).
High frequencies of contact allergy to fragrance ingredients have
been reported. Developments in analytical chemistry have made it
possible to measure exposure to well-known fragrance contact
allergens. Exposure is widespread in different types of products. The
products with the highest concentrations of allergens are prestige
perfumes intended for women. This investigation explores the
possible development in formulation of prestige perfumes, with
regard to their content of the chemically defined ingredients of the
diagnostic patch test material, the fragrance mix (FM). Ten fine
fragrances were subjected to chemical analysis: 5 of these had been
launched years ago (1921-1990) and 5 were the latest launches by
the same companies, introduced 2 months to 4 years before
purchase. The analysis revealed that the 5 old perfumes contained a
mean of 5 of the 7 target allergens of the FM, while the new
perfumes contained a mean of 2.8 of the allergens. The mean
concentrations of the target allergens were 2.6 times higher in the
old perfumes than in the new perfumes, range 2.2-337. It is
concluded that the old perfumes, which are still popular products on
the market, have a different composition from the new perfumes.
This may be due to change in fashion or to an effort by the fragrance
industry to focus on fragrance contact allergy, especially that to the
FM ingredients (2).
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Functional perfumery is an integral part of the fragrance business.

It demands that the ingredients chosen for compounding withstand
the aggressive nature of some of the bases used for soaps,
detergents, softeners, bleach, and personal-care products. The
synthetic efforts in this area reported in this short personal account,
presented in a talk at the RSC/SCI conference Flavours & Fragrances
2004 (Manchester), have resulted in the discovery of the two new
proprietary molecules Fleuranil (5/6) and Khusinil (7), which fulfill the
criteria of functional perfumery. The structure-odor relationships of
several analogs of Fleuranil and Khusinil are prepared in the course of
these investigations (3).
A simple and fast method is proposed to analyze commercial
personal perfumes. This method includes measurement of
phthalates, known to be major sources of endocrine disruptor
chemicals (EDC), which originate from the less volatile fraction of
perfumes. The quantification of phthalates were carried out directly
with no sample preparation required on 30 samples of commercial
products using gas chromatography and mass spectrometry (GC-MS)
as a detector. The total concentrations of 15 investigated
compounds ranged from 17 to 9650 mg/L with an average of 2,643
mg/L. The highest total concentration was found in cologne. Diethyl
phthalate (DEP), diisobutyl phthalate (DiBP), di(2-ethylhexyl)
phthalate (DEHP), and di-n-butyl phthalate (DBP) were detected in
appreciable concentrations. The composition of counterfeit samples
varied widely from that of authentic products. The composition of
old products was different from that of recent perfumes, which
contain less harmful chemicals, attributed to the ban on some
phthalates in Europe due their toxicity. It should be noted that older
and contaminated products are not equivalent to authentic products
when considering quality, safety, and probably effectiveness. Older
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and nonapproved perfumes contain chemicals that are not allowed

for commercial use and may contain toxic impurities (4).
In the last few years, the use of phthalates in perfumes has gained
attention because these chemicals are sometimes added
intentionally as a solvent and a fixative. Five phthalate esters,
dimethyl phthalate (DMP), DEP, dibutyl phthalate (DBP), BBP, and
DEHP, were measured in 47 branded perfumes using headspace solid
phase microextraction (SPME) followed by gas chromatography-mass
spectrometry (GC-MS). The results revealed considerable amounts of
phthalate in all 47 brands with detection frequencies > limit of
quantitation in the following order: DEP (47/47) > DMP (47/47) > BBP
(47/47) > DEHP (46/47) > DBP (23/45). Of the 47 brands, 68.1, 72.3,
85.1, 36.2, and 6.7% had DEP, DMP, BBP, DEHP, and DBP levels,
respectively, above their reported threshold limits. Of these
phthalates, DEP had the highest mean value (1621.625 ppm) and a
maximum of 23,649.247 ppm. The use of DEP in the perfume
industry is not restricted because it does not pose any known health
risks for humans. DMP had the second highest level detected in the
perfumes, with a mean value of 30.202 ppm and a maximum of
405.235 ppm. Although DMP may have some uses in cosmetics, it is
not as commonly used as DEP, and again, there are no restrictions on
its use. The levels of BBP were also high, with a mean value of 8.446
ppm and a maximum of 186.770 ppm. Although the EU banned the
use of BBP in cosmetics, 27 of the tested perfumes had BBP levels
above the threshold limit of 0.1 ppm. The mean value of DEHP found
in this study was 5.962 ppm, and a maximum was 147.536 ppm. In
spite of its prohibition by the EU, 7/28 perfumes manufactured in
European countries had DEHP levels above the threshold limit of 1
ppm. The DBP levels were generally low, with a mean value of 0.0305
ppm and a maximum value of 0.594 ppm. The EU banned the use of
DBP in cosmetics; however, three brands were above the threshold
limit of 0.1 ppm, and all were manufactured in European countries.
The results of this study are alarming and definitely need to be
brought to the attention of the public and health regulators.
Although some phthalate compounds are still used in cosmetics,
many scientists and environmental activists have argued that
phthalates are endocrine-disrupting chemicals that have not been yet
proven to be safe for any use, including cosmetics. Phthalates may
also have different degrees of estrogenic modes of action. We
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should not dismiss the widespread use of phthalates in everyday

products and exposure to these chemicals from sources such as food,
medications, and other personal care products (5).
A novel method for rapid screening of phthalate esters (PAEs) was
developed in perfumes. The PAEs were hydrolyzed to phthalic acid
(PA), and the PA in the acidified solution was extracted with tributyl
phosphate (TBP) which was detected by high performance liquid
chromatography-diode array detection (HPLC-DAD). Meanwhile,
exposure dose to PAEs was estimated by the percentage of a
topically applied dose that permeates the skin. The parameters such
as the concentration and volume of KOH, the volume of ethanol,
hydrolysis time and temperature were employed to evaluate the
hydrolysis efficiency of PAEs. The optimized hydrolysis conditions
were 10 mL of 4 mol/L KOH, and 1 mL of ethanol at 80℃ for 20 min.
The linear range of phthalic acid was 3-240 μmol/L with a good
correlation coefficient (R2=0.9991). The limits of detection (LOD) and
quantification (LOQ) were 4.6 μmol/kg and 5.9 μmol/kg, respectively.
The recoveries varied from 83.4% to 92.7% with relative standard
deviations equal to or lower than 6.8% (n=5). A total of 35 perfume
samples were determined, and the contents of total PAEs were found
in the range of < LOD-77.738 mmol/kg, and the max exposure dose to
PAEs for female adults was 0.4742 μg/(kg·d) through use of
perfumes. The method is simple and reliable, and has a wide range
of applicability. It can be used as a new choice for the detection of
PAEs in perfume (6).
High levels of PAEs added as solvents or fixatives in 47 brands of
perfumes were reported. DEP was the most abundant compound
(0.232-23,649 ppm), and 83.3% of the perfumes had levels >1 ppm,
the threshold limit cited by a Greenpeace investigation. All samples
had dimethyl phthalate levels higher than its threshold limit of 0.1
ppm, and 88, 38, and 7% of the perfumes had benzyl butyl phthalate,
di(2-ethylhexyl) phthalate, and dibutyl phthalate levels, respectively,
above their threshold limits. The role of PAEs as endocrine disruptors
has been well documented, but their effect on genotoxic behavior
has received little attention. In vitro single-cell gel electrophoresis
(comet) and micronucleus (MN) assays with human lymphoblastoid
TK6 cells were used to evaluate the genotoxic potency of 42 of the
same perfumes and to determine its association with PAEs. All
perfumes induced more DNA damage than a negative control (NEG),
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≥ 90% of the samples caused more damage than cells treated with
the vehicles possibly used in perfume's preparations such as
methanol (ME) and ethanol (ET), and 11.6% of the perfumes caused
more DNA damage than a positive control (hydrogen peroxide).
Chromosome breakage expressed as MN frequency was higher in
cells treated with 71.4, 64.3, 57.1, and 4.8% of the perfumes than in
NEG, cells treated with ME or ET, and another positive control (x-
rays), respectively. The genotoxic responses in the comet and MN
assays were not correlated. The comet assay indicated that the
damage in TK6 cells treated with five PAEs at concentrations of 0.05
and 0.2 ppm either individually or as a mixture did not differ
significantly from the damage in cells treated with the perfumes.
Unlike the comet assay, the sensitivity of the MN assay to PAEs was
weak at both low and high concentrations, and MN frequencies were
generally low. This study demonstrates the possible contribution of
PAEs in perfumes to DNA damage and suggests that their use as
solvents or fixatives should be regulated. Other ingredients with
mutagenic/genotoxic properties, however, may also have
contributed to the DNA damage (7).
Findings suggest that long-term exposure to DEP, one of the
widely used PAEs, can lead to serious health problems. Most
perfumes contain non-negligible amounts of DEP. Rapid and
sensitive detection of DEP in perfumes is thus of increasing
importance. A novel procedure based on extractive electrospray
ionization mass spectrometry (EESI-MS) has been developed for fast
detection and identification of DEP in perfumes without the need for
any sample pretreatment. The limit of determination for DEP in
perfume was less than 100 ppb using tandem mass spectrometry on
a commercial quadrupole time-of-flight mass spectrometer. The
dynamic range of this method was about 4 orders of magnitude. A
single sample analysis was completed within a few seconds, providing
a rapid way to obtain semiquantitative information on the DEP
content in perfumes. This study shows that both volatile and
nonvolatile analytes (e.g., amino acids) in liquids can be directly
sampled by neutral desorption, providing a convenient way for high-
throughput screening of target compounds using EESI-MS (8).
High levels of phthalates in name-brand cosmetics products have
raised concerns about phthalate exposure and the associated risk for
cosmetics sales clerks. The exposure and risk of phthalates in 23
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cosmetics, 4 perfume, and 9 clothing department store sales clerks

were assessed. Totally, 108 urine samples pre- and post-shift were
collected and analyzed for phthalate monoesters through liquid
chromatography-electrospray ionization-tandem mass spectrometry.
Phthalates in 32 air samples were collected and analyzed through gas
chromatography-mass spectrometry. Demographic characteristics
and information on the exposure scenarios were obtained through
questionnaires. Principal component analysis, cluster and risk
analysis were applied to identify the exposure profile and risk of
phthalate. Median post-shift levels of urinary mono-2-ethylhexyl
phthalate (MEHP) and monomethyl phthalate (MMP) were
significantly higher than the corresponding pre-shift levels in
cosmetics group (53.3 vs. 30.9 μg/g-c for MEHP; 34.4 vs. 22.5 μg/g-c
for MMP; both p<0.05) and the post-shift levels of urinary MMP was
significantly higher than the corresponding pre-shift levels in perfume
group (26.6 vs. 14.9 μg/g-c, p<0.05). Median levels of air DEP in
cosmetics (1.77 μg/m3) and perfume (1.75 μg/m3) groups and di-(2-
ethylhexyl) phthalate (DEHP) in perfume group (6.98 μg/m3) were
higher than those in clothing group (DEP: 0.89; DEHP: 2.16 μg/m3).
Over half of cosmetic (70%) and perfume sale clerks had exceeded
cumulative risk of phthalate exposure for anti-androgenic effect. In
conclusion, cosmetic and perfume workers had increased risks of
reproductive or hepatic effects for DBP and DEHP exposure. Not only
inhalation but dermal exposure is important route of phthalate
exposure for cosmetics and perfume workers (9).
High-performance liquid chromatography (HPLC) with UV/VIS
spectrophotometric detection combined with the chemometric
method of cluster analysis (CA) was used for the assessment of
repeatability of composition of nine types of perfumed waters. In
addition, the chromatographic method of separating components of
the perfume waters under analysis was subjected to an optimization
procedure. The chromatograms thus obtained were used as sources
of data for the chemometric method of CA. The result was a
classification of a set comprising 39 perfumed water samples with a
similar composition at a specified level of probability (level of
agglomeration). A comparison of the classification with the
manufacturer's declarations reveals a good degree of consistency
and demonstrates similarity between samples in different classes. A
combination of the chromatographic method with cluster analysis
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(HPLC UV/VIS - CA) makes it possible to quickly assess the

repeatability of composition of perfumed waters at selected levels of
probability (10).
Three covalent anthocyanin-flavonol complexes (pigments 1-3)
were extracted from the violet-blue flower of Allium 'Blue Perfume'
with 5% acetic acid-MeOH solution, in which pigment 1 was the
dominant pigment. These three pigments are based on delphinidin
3-glucoside as their deacylanthocyanin and were acylated with
malonyl kaempferol 3-sophoroside-7-glucosiduronic acid or malonyl-
kaempferol 3-p-coumaroyl-tetraglycoside-7-glucosiduronic acid in
addition to acylation with acetic acid. By spectroscopic and chemical
methods, the structures of these three pigments 1-3 were
determined to be: pigment 1, (6(I)-O-(delphinidin 3-O-(3(I)-O-(acetyl)-
β-glucopyranoside(I))))(2(VI)-O-(kaempferol 3-O-(2(II)-O-(3(III)-O-(β-
glucopyranosyl(V))-β-glucopyranosyl(III))-4(II)-O-(trans-p-coumaroyl)-
6(II)-O-(β-glucopyranosyl(IV))-β-glucopyranoside(II))-7-O-(β-
glucosiduronic acid(VI)))) malonate; pigment 2, (6(I)-O-(delphinidin 3-
O-(3(I)-O-(acetyl)-β-glucopyranoside(I))))(2(VI)-O-(kaempferol 3-O-
(2(II)-O-β-glucopyranosyl(III))-β-glucopyranoside(II))-7-O-(β-
lucosiduronic acid(VI)))); and pigment 3, (6(I)-O-(delphinidin 3-O-(3(I)-
O-(acetyl)-β-glucopyranoside(I))))(2(VI)-O-(kaempferol 3-O-(2(II)-O-
(3(III)-O-(β-glucopyranosyl(V))-β-glucopyranosyl(III))-4(II)-O-(cis-p-
coumaroyl)-6(II)-O-(β-glucopyranosyl(IV))-β-glucopyranoside(II))-7-O-
(β-glucosiduronic acid(VI)))) malonate. The structure of pigment 2
was analogous to that of a covalent anthocyanin-flavonol complex
isolated from Allium schoenoprasum where delphinidin was
observed in place of cyanidin. The three covalent anthocyanin-
flavonol complexes (pigment 1-3) had a stable violet-blue color with
three characteristic absorption maxima at 540, 547 and 618 nm in pH
5-6 buffer solution. From circular dichroism measurement of
pigment 1 in the pH 6.0 buffer solution, cotton effects were observed
at 533 (+), 604 (-) and 638 (-) nm. Based on these results, these
covalent anthocyanin-flavonol complexes were presumed to
maintain a stable intramolecular association between delphinidin and
kaempferol units closely related to that observed between
anthocyanin and hydroxycinnamic acid residues in polyacylated
anthocyanins. Additionally, an acylated kaempferol glycoside
(pigment 4) was isolated from the same flower extract, and its
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structure was determined to be kaempferol 3-O-sophoroside-7-O-(3-

O-(malonyl)-β-glucopyranosiduronic acid) (11).
Sclareol is a diterpene natural product of high value for the
fragrance industry. Its labdane carbon skeleton and its two hydroxyl
groups also make it a valued starting material for semisynthesis of
numerous commercial substances, including production of Ambrox®
and related ambergris substitutes used in the formulation of high end
perfumes. Most of the commercially-produced sclareol is derived
from cultivated clary sage (Salvia sclarea) and extraction of the plant
material. In clary sage, sclareol mainly accumulates in essential oil-
producing trichomes that densely cover flower calices. Manool also
is a minor diterpene of this species and the main diterpene of related
Salvia species. Based on previous general knowledge of diterpene
biosynthesis in angiosperms and on mining of the recently published
transcriptome database obtained by deep 454-sequencing of cDNA
from clary sage calices, we cloned and functionally characterized two
new diterpene synthase (diTPS) enzymes for the complete
biosynthesis of sclareol in clary sage. A class II diTPS (SsLPPS)
produced labda-13-en-8-ol diphosphate as major product from
geranylgeranyl diphosphate (GGPP) with some minor quantities of its
non-hydroxylated analogue, (9 S, 10 S)-copalyl diphosphate. A class I
diTPS (SsSS) then transformed these intermediates into sclareol and
manool, respectively. The production of sclareol was reconstructed
in vitro by combining the two recombinant diTPS enzymes with the
GGPP starting substrate and in vivo by co-expression of the two
proteins in yeast (Saccharomyces cerevisiae). Tobacco-based
transient expression assays of green fluorescent protein-fusion
constructs revealed that both enzymes possess an N-terminal signal
sequence that actively targets SsLPPS and SsSS to the chloroplast, a
major site of GGPP and diterpene production in plants. In conclusion,
SsLPPS and SsSS are two monofunctional diTPSs which, together,
produce the diterpenoid specialized metabolite sclareol in a two-step
process. They represent two of the first characterized hydroxylating
diTPSs in angiosperms and generate the dihydroxylated labdane
sclareol without requirement for additional enzymatic oxidation by
activities such as cytochrome P450 monoxygenases. Yeast-based
production of sclareol by co-expresssion of SsLPPS and SsSS is
efficient enough to warrant the development and use of such
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technology for the biotechnological production of scareol and other

oxygenated diterpenes (12).
In the thermal village of Monchique, Algarve, different streams of
water-related knowledge and practices coexist for centuries. Those
waters are traditionally known as aguas santas (holy waters) and
believed to have redemptive healing powers. In the seventeenth
century, the Catholic Church took control of the place, refashioned
the bathing rituals, developed infrastructures and provided
assistance to the patients, granting free treatment to the poor. In the
nineteenth century, the state replaced the church and imposed that
treatments should be provided by professionals trained in the
scientific principles of medical hydrology. Secular and scientific as
they were, clinical logbooks still allowed for the account of patients
that embodied miracle-like redemptive cures 'at the third bath'.
People went to Monchique both for its magic and its medicine,
bringing in the body ailments achieved in their lives of hard labour.
They also went there for a socializing break while healing. From
mendicants to rich landowners, coming mostly from the Algarve and
neighboring Alentejo, they crowded the place in summertime. In the
twentieth century, as in other places in continental Europe, the spa
evolved into a highly musicalized place that qualified for medical
expenses reimbursements, which implied the eclipsing - at least from
representation - of its leisure component. In the twenty-first century,
a new trend of consumer-centered, market-based, post-water
balneology with an emphasis on wellness and leisure reinvented the
spa as place for lush and diversified consumption. The seemingly
contradictory systems (markets and medicine) coexist much in the
same way that magic, religion and medicine coexist in the old water
sites. The new SPAs, rather than putting an end to the old spas, have
enabled them to survive by reinventing thermal sites as places of
attraction and leisure (13).
Terpenoids represent a large class of natural products with
significant commercial applications. These chemicals are currently
obtained through extraction from plants and microbes or through
chemical synthesis. However, these sources often face challenges of
unsustainability and low productivity. In order to address these
issues, Escherichia coli and yeast have been metabolic engineered to
produce non-native terpenoids. With recent reports of engineering
yeast metabolism to produce several terpenoids at high yields, it has
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become possible to establish commercial yeast production of

terpenoids that find applications as perfume ingredients,
pharmaceuticals and advanced biofuels. The strategies rewire the
yeast pathway for terpenoid biosynthesis (14).
A series of thioether profragrances was prepared by reaction of
different sulfanylalkanoates with δ-damascone and tested for their
release efficiencies in a fabric-softener and an all-purpose cleaner
application. Dynamic headspace analysis on dry cotton and on a
ceramic plate revealed that the performance of the different
precursors depended on the structure, but also on the particular
conditions encountered in different applications. Profragrances
derived from other α,β-unsaturated fragrance aldehydes and ketones
were synthesized analogously and evaluated using the same test
protocol. Thioethers were found to be suitable precursors to release
the corresponding fragrances, but neither the quantity of
profragrance deposited from an aqueous environment onto the
target surface, nor the amount of fragrance released after deposition
could be linearly correlated to the hydrophilicity or hydrophobicity of
the compounds. Different sets of compounds were the best
performers for different types of applications. Only one of the
compounds evaluated in the present work, namely the thiolactic acid
derivative of δ-damascone, efficiently released the corresponding
fragrance in both of the tested applications. Profragrance
development for functional perfumery thus remains a partially
empirical endeavour. More knowledge (and control) of the various
application conditions are required for an efficient profragrance
design (15).
Carbon monoxide (CO) is a colorless, odorless gas with a
reputation for being an anthropogenic poison; there is extensive
documentation of the modes of human exposure, toxicokinetics, and
health effects. However, CO is also generated endogenously by
heme oxygenases (HOs) in mammals and microbes, and its
extraordinary biological activities are recognized and increasingly
utilized in medicine and physiology. This review introduces recent
advances in CO biology and chemistry and illustrates the exciting
possibilities that exist for a deeper understanding of its biological
consequences. However, the microbiological literature is scant and is
currently restricted to: 1] CO-metabolizing bacteria, CO oxidation by
CO dehydrogenase (CODH) and the CO-sensing mechanisms that
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enable CO oxidation; 2] the use of CO as a heme ligand in microbial

biochemistry; and 3] very limited information on how microbes
respond to CO toxicity. The horizons in CO biology have been
extended by intense research activity in recent years in mammalian
and human physiology and biochemistry. CO is one of several "new"
small gas molecules that are increasingly recognized for their
profound and often beneficial biological activities, the others being
nitric oxide (NO) and hydrogen sulfide (H2S). An important advance
in recent years has been the development of CO-releasing molecules
(CO-RMs) for aiding experimental administration of CO as an
alternative to the use of CO gas. The chemical principles of CO-RM
design and mechanisms of CO release from CO-RMs (dissociation,
association, reduction and oxidation, photolysis, and acidification)
are reviewed and a survey of the most commonly used CO-RMs is
presented. Amongst the most important new applications of CO in
mammalian physiology and medicine are its vasoactive properties
and the therapeutic potentials of CO-RMs in vascular disease, anti-
inflammatory effects, CO-mediated cell signaling in apoptosis,
applications in organ preservation, and the effects of CO on
mitochondrial function. There is very limited literature on microbial
growth responses to CO and CO-RMs in vitro, and the transcriptomic
and physiological consequences of microbial exposure to CO and CO-
RMs. There is current interest in CO and CO-RMs as antimicrobial
agents, particularly in the control of bacterial infections (16).
Ylang-ylang (Cananga odorata Hook. F. & Thomson) is one of the
plants that are exploited at a large scale for its essential oil which is
an important raw material for the fragrance industry. The essential
oils extracted via steam distillation from the plant have been used
mainly in cosmetic industry but also in food industry. Traditionally, C.
odorata is used to treat malaria, stomach ailments, asthma, gout, and
rheumatism. The essential oils or ylang-ylang oil is used in
aromatherapy and is believed to be effective in treating depression,
high blood pressure, and anxiety. Many phytochemical studies have
identified the constituents present in the essential oils of C. odorata.
A wide range of chemical compounds including monoterpene,
sesquiterpenes, and phenylpropanoids have been isolated from this
plant. Studies have shown a wide variety of bioactivities exhibited by
the essential oils and the extracts of C. odorata including
antimicrobial, antibiofilm, anti-inflammatory, antivector, insect-
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repellent, antidiabetic, antifertility and antimelanogenesis activities.

The information concerning the traditional uses, phytochemistry, and
biological activities of C. odorata is summarized. In conclusion, C.
odorata not only is an important raw material for perfume industry
but also considered as a prospective useful plant to agriculture and
medicine (17).
Over the past decade, there has been growing interest within
ethnobiology in the knowledge and practices of migrating people.
Within this, scholars have given relatively less attention to displaced
people and refugees: to the loss, maintenance, and adaptation of
refugees' ethnobiological knowledge, and to its significance for
refugees' wellbeing. This study focuses on cosmetics and remedies
used to heal skin afflictions that are traditionally used by Sahrawi
refugees displaced in South Western Algerian refugee camps. The
research methods included a structured survey carried out with 37
refugee households, semi-structured interviews with 77 refugees, 24
retrospective interviews with refugees and other knowledgeable
informants, and a voucher specimen collection of the plants and
products cited. The use of 55 plant species, nine animal species, and
six mineral products were used within the three main use categories
discussed in this paper: 1] Remedies for health issues that are typical
of the desert environment where the Sahrawi once lived as nomads
and now live as refugees (e.g. eye afflictions); 2] Remedies for
wounds that are influenced by the Sahrawi's recent history of
guerrilla warfare; and 3] Cosmetics and products used for body care,
decoration and perfuming (e.g. hair care, teeth cleansing, henna use)
and for aromatizing the air inside of tents and which are widely used
in everyday life and social practices. In conclusion, the changes have
occurred in the patterns of use and procurement of these products
with exile and sedentarization in refugee camps, and refugees are not
simply passive recipients of national and international aid, but rather
struggle to maintain and recover their traditional ethnobiological
practices in exile (18).

ASSESSMENT: different sets of ingredients are the best

performers for different types of perfume applications. Some of
these ingredients are toxic to humans.

References
 43

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1. Ellena C. Perfume formulation: words and chats. Chem Biodivers.

2008;5(6):1147-53.
2. Rastogi SC, Menné T, Johansen JD. The composition of fine fragrances is
changing. Contact Dermatitis. 2003;48(3):130-2.
3. Narula AP. The search for new fragrance ingredients for functional
perfumery. Chem Biodivers. 2004;1(12):1992-2000.
4. Orecchio S, Indelicato R, Barreca S. Determination of selected phthalates by
gas chromatography-mass spectrometry in personal perfumes. J Toxicol Environ
Health A. 2015;78(15):1008-18.
5. Al-Saleh I, Elkhatib R. Screening of phthalate esters in 47 branded perfumes.
Environ Sci Pollut Res Int. 2016;23(1):455-68.
6. Zhao S, Wang Z, Deng H, et al. Determination of total phthalates in perfume
and their exposure assessment. Se Pu. 2017;35(12):1301-5.
7. Al-Saleh I, Al-Rajudi T, Al-Qudaihi G, Manogaran P. Evaluating the potential
genotoxicity of phthalates esters (PAEs) in perfumes using in vitro assays. Environ
Sci Pollut Res Int. 2017;24(30):23903-14.
8. Chingin K, Chen H, Gamez G, et al. Detection of diethyl phthalate in
perfumes by extractive electrospray ionization mass spectrometry. Anal Chem.
2009;81(1):123-9 Erratum in Anal Chem. 2009;81(6):2414.
9. Huang PC, Liao KW, Chang JW, et al. Characterization of phthalates
exposure and risk for cosmetics and perfume sales clerks. Environ Pollut.
2018;233:577-87.
10. Ruzik L, Obarski N, Papierz A, Mojski M. Assessment of repeatability of
composition of perfumed waters by high-performance liquid chromatography
combined with numerical data analysis based on cluster analysis (HPLC UV/VIS -
CA). Int J Cosmet Sci. 2015;37(3):348-56.
11. Saito N, Nakamura M, Shinoda K, et al. Covalent anthocyanin-flavonol
complexes from the violet-blue flowers of Allium 'Blue Perfume'. Phytochemistry.
2012;80:99-108.
12. Caniard A, Zerbe P, Legrand S, et al. Discovery and functional
characterization of two diterpene synthases for sclareol biosynthesis in Salvia
sclarea (L.) and their relevance for perfume manufacture. BMC Plant Biol.
2012;12:119.
13. Bastos C. From sulphur to perfume: spa and SPA at Monchique, Algarve.
Anthropol Med. 2011;18(1):37-53.
14. Zhang Y, Nielsen J, Liu Z. Engineering yeast metabolism for production of
terpenoids for use as perfume ingredients, pharmaceuticals and biofuels. FEMS
Yeast Res. 2017 Dec 1;17(8).
15. Maddalena U, Trachsel A, Fankhauser P, et al. Thioether profragrances:
parameters influencing the performance of precursor-based fragrance delivery in
functional perfumery. Chem Biodivers. 2014;11(11):1700-33.
16. Davidge KS, Motterlini R, Mann BE, et al. Carbon monoxide in biology and
microbiology: surprising roles for the "Detroit perfume". Adv Microb Physiol.
2009;56:85-167.
17. Tan LT, Lee LH, Yin WF, et al. Traditional uses, phytochemistry, and
bioactivities of Cananga odorata (Ylang-Ylang). Evid Based Complement Alternat
Med. 2015;2015:896314.
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18. Volpato G, Kourková P, Zelený V. Healing war wounds and perfuming

exile: the use of vegetal, animal, and mineral products for perfumes, cosmetics,
and skin healing among Sahrawi refugees of Western Sahara. J Ethnobiol
Ethnomed. 2012 Dec 27;8:49.

FRAGRANCE CONCENTRATIONS
A fragrance concentration refers to the strength that a fragrance
has. Perfumes with a higher fragrance concentration contain more
perfume oils and less alcohol. Fragrance concentrations are broken
into categories including parfum, eau de parfum, eau de toilette, eau
de cologne, and eau fraiche (1):

PARFUM
Parfum, also known as extrait de parfum or pure perfume, has the
highest fragrance concentration. Parfum contains from 15% to 40%
fragrance however, concentration is generally between 20% to 30%
for most parfums. Of all scents, parfums last the longest; usually six
to eight hours. Parfum generally also commands the highest price of
all the fragrance types due to the high concentration of fragrance.
People with sensitive skin may do better with parfums as they have
far less alcohol than other fragrance types and therefore are not as
likely to dry out the skin.

EAU DE PARFUM
After parfum, eau de parfum has the next highest concentration
of fragrance. Eau de parfum generally has a fragrance concentration
of between 15% and 20%. On average, the scent of eau de parfum
 45

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will last for four to five hours. It is generally less expensive that
parfum and while it does have a higher concentration of alcohol than
parfum, it is better for sensitive skin than other fragrance types. Eau
de parfum is one of the most common fragrance types and is suitable
for everyday wear.

EAU DE TOILETTE
Eau de toilette has a fragrance concentration of between 5% and
15%. It is cheaper than eau de parfum and is one of the most
popular types of fragrance available. Eau de toilette fragrance
normally lasts for two to three hours.

Eau de toilette is considered by some to be for daywear while eau

de parfum is considered nightwear. The term eau de toilette came
from the French term "faire sa toilette" which means getting ready.

EAU DE COLOGNE
Eau de cologne has a much lower concentration of fragrance than
the above types of perfume, generally a 2% to 4% percent
concentration of fragrance and a high concentration of alcohol. It is
cheaper than other types of fragrance however, the scent generally
lasts for up to two hours. Eau de cologne generally comes in bigger
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bottles and more of the fragrance needs to be used. Originally eau

de cologne referred to a traditional recipe that used herb and citrus
notes.

Original Eau de Cologne flacon 1811, from Johann Maria Farina,

Farina gegenüber.

EAU FRAICHE
Eau fraiche is similar to eau de cologne in that the scent generally
lasts for up to two hours. Eau fraiche has an even lower
concentration of fragrance than eau de cologne, normally only 1% to
3%. While eau fraiche has a low fragrance concentration, it does not
contain a high amount of alcohol. Along with the fragrance, the
remainder of eau fraiche is mostly water.

Along with the types of perfume listed above, there are mists,
aftershaves, and other types of fragrances available. Higher end
fragrances can cost a significant amount of money so doing research
beforehand will ensure that he/she gets the type of fragrance he/she
is looking for. Along with fragrance types there are also fragrance
notes which determine the final scent. With all of the types and
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scents available, shopping for perfume is not always easy but it is

possible.

Reference
1. A Guide to Perfume Types. Available 10 March 2018 at
perfume.com/article-a-guide-to-perfume-types.

FRAGRANCE SENSITIZERS
This study determined the percentages of individuals who report
adverse effects from exposure to fragranced products in the U.S.
population and in subpopulations of those with asthma or chemical
sensitivity. Data were collected through telephone interviews from
two geographically weighted, random samples of the continental U.S.
in two surveys during 2002-2003 and 2005-2006 (1,057 and 1,058
cases, respectively). Respondents were asked if they find being next
to someone wearing a scented product irritating or appealing; if they
have headaches, breathing difficulties, or other problems when
exposed to air fresheners or deodorizers; and if they are irritated by
the scent from laundry products, fabric softeners, or dryer sheets
that are vented outside. Results aggregated from both surveys found
that 30.5% of the general population reported scented products on
others irritating, 19% reported adverse health effects from air
fresheners, and 10.9% reported irritation by scented laundry
products vented outside. This study reveals that a considerable
percentage of the U.S. population reports adverse health effects or
irritation from fragranced products, with higher percentages among
those with asthma and chemical sensitivity (1).
The prevalence of sensitization to fragrance mix (FM) I and
Myroxylon pereirae (MP, balsam of Peru) has decreased in recent
years among Danish women with dermatitis. This study investigated
whether the decrease could be confirmed among women in the
general population. It addressed the morbidity of FM I sensitization.
In 1990, 1998 and 2006, 4,299 individuals aged 18-69 years (18-41
years only in 1998) completed a premailed questionnaire and were
patch tested to FM I and MP. Data were analyzed by logistic
regression analyses and associations were expressed as odds ratio
[OR] with 95% confidence intervals [CI]. The prevalence of FM I and
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MP sensitization followed an inverted V-pattern among women aged

18-41 years (i.e. an increase from 1990 to 1998, followed by a
decrease from 1998 to 2006). Logistic regression analyses showed
that 'medical consultation due to cosmetic dermatitis' (OR 3.37, 95%
CI 1.83-6.20) and 'cosmetic dermatitis within the past 12 months' (OR
3.53, 95% CI 2.02-6.17) were significantly associated with
sensitization to FM I. In conclusion, in line with trends observed in
Danish patients with dermatitis, the results supported a recent
decrease in the prevalence of FM I and MP sensitization in Denmark.
The study also showed that fragrance sensitization was associated
with self-reported cosmetic dermatitis and use of health care related
to cosmetic dermatitis (2).
Contact allergy to fragrance ingredients is frequent.
Recommendations and regulations of some of the most frequent and
potent fragrance allergens have recently been introduced. Exposures
were investigated to 4 important fragrance allergens in
hydroalcoholic cosmetic products. Twenty five popular perfume
products of Danish as well as international brands were purchased
from the Danish retail market. Contents of 4 important fragrance
allergens, isoeugenol, hydroxy-iso-hexyl 3-cyclohexene
carboxaldehyde (HICC, Lyral), were determined by gas
chromatography-mass spectrometry, and atranol and chloro-atranol
were determined by liquid chromatography-tandem mass
spectrometry. Isoeugenol was found in 56%, HICC in 72%, atranol in
59%, and chloro-atranol in 36% of the 22 eau de toilette/eau de
parfum products. The concentrations of isoeugenol were, in all
products, below the recommended maximum concentration of
0.02%. HICC reached a maximum of 0.2%, which is 10-fold higher
than maximum tolerable concentration considered safe by the EU
Scientific Committee. The median concentrations of atranol and
chloro-atranol in the investigated products were similar to those
found in similar products in 2003. A significant decrease in the
frequency of presence of chloro-atranol in the products was
observed. There is still a wide-spread exposure to potent fragrance
allergens in perfumes (3).
Isoeugenol, an important fragrance allergen in consumers, has
been restricted to 200 p.p.m. since 1998 according to guidelines
issued by the fragrance industry. However, no decline in contact
allergy to isoeugnol has been detected. It has been speculated that
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isoeugenol derivatives, especially isoeugenyl acetate, are used

instead. Isoeugenyl acetate is probably metabolized in the skin to
isoeugenol and gives positive patch test reactions in 1/3 of
isoeugenol-sensitized individuals. The content of isoeugenol,
isoeugenyl acetate, and two isoeugenol ethers were investigated in
perfumes/aftershaves. Twenty nine international brand perfumes/
aftershaves were analyzed for the target fragrance ingredient by gas
chromatography-mass spectrometry. All samples were analyzed in
duplicate at detection levels of 1-5 p.p.m. Sixteen products (55%)
contained isoeugenol. The maximum concentration was 202 p.p.m.
10 products (34%) contained isoeugenyl acetate, which in 9 cases
occurred together with isoeugenol. The concentrations of isoeugenyl
acetate ranged from 20 to 4689 p.p.m. 13 products (44%) contained
64.9-1755.0 p.p.m. isoeugenyl methyl ether. Isoeugenyl benzyl ether
was not detected in any of the investigated products. In conclusion,
soeugenyl acetate is present in perfumes/aftershaves, in some
products in significant amounts. This may lead to elicitation of
contact allergy in isoeugenol-sensitized individuals and may
contribute to unchanged levels of isoeugenol sensitization (4).
The prevalence of contact allergy to the FM in individuals with
eczema is up to 10%. Within the mix, isoeugenol (CAS 97-54-1) is an
important individual allergen. Until May 1998, the IFRA
(International Fragrance Association) guidelines suggested that
isoeugenol could safely be used at a level of 0.2% in consumer
products. In May 1998, IFRA recommended that isoeugenol should
not be used at a level that exceeds 0.02% in consumer products, but
did not provide guidance on allergen substitution. An alternative to
isoeugenol, based on aroma and absence of guidelines on use, is
isoeugenyl acetate (CAS 93-29-8). Totally, 155 consecutive subjects
were patch tested to isoeugenyl acetate (1.2%, 0.4%, 0.13% eth.) and
isoeugenol 1% pet. 6 (3.9%) had an allergic reaction to 1.2%
isoeugenyl acetate at D4. The reactions to the other 2 dilutions
tended to be graded. Eight individuals had at least a palpable
erythema by D4 to isoeugenol 1% pet. The majority of individuals
allergic to isoeugenol were also intolerant of isoeugenyl acetate.
Effective labelling of fragrance substances on consumer products will
facilitate monitoring of exposure (5).
Chloroatranol and atranol have been identified as the main
allergens in the fragrance material of botanical origin, oak moss
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absolute. A previous study has shown that nearly all individuals

sensitized to chloroatranol will elicit to 5 microg/ml. in a repeated
open application test and that 50% will get a reaction to 0.15 micro
g/ml under patch test conditions. Thus, chloroatranol is known as a
potent allergen. The aim of the current investigation was to quantify
exposure to chloroatranol and the chemically related substance
atranol in some popular perfumes, eaux de parfum and eaux de
toilette available on the European market. In total, 31 products were
analyzed by liquid chromatography-electrospray ionization-
tandemmass spectrometry (LC-ESI-MS-MS) for their contents of
atranol and chloroatranol. The 2 substances were found in 87%
(n=27) of the products. The median concentration of atranol in
perfumes was 0.502 micro g/ ml and 0.012 micro g/ml in eaux de
toilette, and 0.235 micro g/ml and 0.006 micro g/ml for
chloroatranol, respectively, in perfume and eaux de toilette.
Chloroatranol was found at a maximum concentration of 53 micro
g/ml and atranol at one of 190 micro g/ml. The wide exposure to oak
moss allergens, together with significant amounts of these potent
allergens in at least half of perfumes and some eau de toilettes
explains the high frequencies of oak moss absolute allergy. It is
suggested that regulations should be introduced aimed directly at
these substances, and not just at oak moss absolute (6).
Some fragrance substances have the potential to cause skin
sensitization associated with the development of allergic contact
dermatitis (ACD). Fragrances are invariably relatively volatile leading
to the consideration that inhalation of fragrances might be a relevant
route for either the induction of allergic sensitization or the
elicitation of allergic reactions. Moreover, there has been increasing
recognition that allergic sensitization of the respiratory tract can be
induced by topical exposure to certain chemical allergens. Here the
central question addressed is whether inhalation exposure to
fragrance allergens has the potential to cause skin and/or respiratory
sensitization via the respiratory tract, or elicit allergic symptoms in
those already sensitized. In addressing those questions, the
underlying immunobiology of skin and respiratory sensitization to
chemicals has been reviewed briefly, and the relevant experimental
and clinical evidence considered. The essential mechanistic
differences between skin and respiratory allergy appear consistent
with other sources of information, including the phenomenon of ACD
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that can arise from topical exposure to airborne allergens, but in the
absence of accompanying respiratory effects. In conclusion, in
contrast to topical exposure (including topical exposure to airborne
material), inhalation of fragrance sensitizers does not represent a
health risk with respect to allergy (7).
The induction of contact allergy to fragrance ingredients and the
consequent risk of ACD present a human health concern that cannot
be ignored. The problem arises when exposure exceeds safe levels,
but the source(s) of exposure which lead to induction often remain
unclear. This contrasts with the elicitation of ACD, where the eczema
frequently can be traced to specific source(s) of skin exposure.
Cosmetic products are often implicated, both for induction and
elicitation. However, other products contain fragrance ingredients,
including household cleaning products. The risk assessment
concerning the ability of these products to induce fragrance contact
allergy is considered and the clinical evidence for the induction
and/or elicitation of ACD is reviewed. It can be concluded that the
risk of the induction of fragrance contact allergy from household
cleaning products is low. Especially where more potent fragrance
allergens are used in higher exposure products, the aggregated
exposure from such products can augment the risk for the elicitation
of ACD. This supports the need to manage this risk via the provision
of information to consumers (8).
The use of cosmetics exposes consumers to mixtures of
ingredients, many of which are contact allergens. Fragrances in
particular are mostly used in combination; combinations of
fragrances have been shown to enhance sensitization and elicitation.
The pattern of co-exposure to fragrances was examined in different
categories of cosmetics, addressing the 26 fragrances that need to be
identified on the label according to the Cosmetics Directive
76/768/EEC amended by 2003/15/EC. A survey of products
marketed in Germany, conducted in 2006-2009 by the Chemical and
Veterinary Investigation Office in Karlsruhe, identified 4,991 products
with information on the presence of fragrances. The products were
categorized according to Annex I to the Cosmetics Directive. The
occurrence and co-occurrence of fragrances were analyzed in tabular
form and as social network diagrams. The median number of
fragrances in products varied greatly between categories, ranging up
to nine in perfumes. Limonene and linalool were the most commonly
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identified fragrances, often used together, but also with other

fragrances. Thirty per cent of all products were not declared to
contain any fragrances. In conclusion, the pattern of co-exposure to
fragrance ingredients in important categories of cosmetic products
has been described. The observations illustrate and quantify the
'cocktail' of fragrance allergens that may facilitate sensitization (9).
Exposure to fragrances is increasingly encountered in the
environment. Some fragrances are known to be important skin and
potential airway sensitizers. Whether patients with contact allergy to
isoeugenol or hydroxyisohexyl-3-carboxaldehyde (HICC) would react
to inhalation exposure was investigated at the level of the airways
and skin. Eleven patients sensitized to isoeugenol and 10 patients
sensitized to HICC were exposed for 60 min to 1000 microg m(-3) of
these compounds in an exposure chamber at rest, and to geraniol
1000 microg m(-3) as a control. Patients wore protective clothing to
prevent skin exposure. Assessments were performed prior to
exposure, and immediately, 2, 5, 24 and 72 h afterwards. There were
insignificant changes in lung function but a tendency towards an
increased bronchial hyper-responsiveness after exposure to any of
the compounds. Laboratory parameters of inflammation did not
indicate responses. Single patients reported respiratory symptoms
unrelated to objective measures. In contrast, the observed skin
symptoms corresponded to the patients' specific sensitization. Four
patients reported symptoms compatible with delayed-type
hypersensitivity, and two demonstrated a flare after isoeugenol. On
re-exposure they did not respond to a lower, more realistic level of
isoeugenol. In conclusion, inhalation of high concentrations of
fragrance contact allergens apparently poses a risk for some patients
of developing manifest haematogenic contact dermatitis, while the
changes in the respiratory tract are limited to symptoms in some
subjects without objective changes (10).
Contact allergy to fragrances is a common problem world-wide.
The currently used FM for patch testing has only eight constituents
and does not identify all fragrance-allergic patients. As perfumes
may contain 100 or more substances, the search for markers for
allergy continues. The synthetic fragrance 4-(4-hydroxy-4-
methylpentyl)-3-cyclohexene carboxaldehyde (Lyral) was tested
together with the FM and 11 other fragrance substances on
consecutive patients in six European departments of dermatology.
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All patients were carefully questioned regarding a history of reactions

to scented products in the past and were grouped into four
categories: 'certain', 'probable', 'questionable' and 'none'. Lyral (5%
in petrolatum) gave a positive reaction in 2.7% of 1,855 patients
(range 1.2-17%) and ranked next to 11.3% with FM allergy. Twenty-
four patients reacted to both Lyral and FM, but 21 (1.1%) reacted
positively only to Lyral. Of 124 patients with a 'certain' history, 53.2%
reacted to the FM and a further 7.2% to Lyral only. If any kind of
history of fragrance intolerance was given, 80% (40 of 50) of Lyral
positive patients had a 'positive' history while only 58.6% (123 of 210)
of FM positive patients had such a history; this difference was
significant at p<0.01. Lyral was identified by gas chromatography-
mass spectrometry in some products which had caused an ACD in
four typical patients who showed a patch test positive to Lyral and
negative or doubtful to FM. In conclusion, the testing of 5% Lyral (in
petrolatum) is recommended in patients suspected of contact
dermatitis (11).
Fragrances are a common cause of contact dermatitis and account
for a large percentage of reactions to cosmetic products. Novel
fragrance compounds that may not be detected by the common
fragrance screening agents (including balsam of Peru and FM) are
continually being produced. Lyral is one of those allergens found in
many cosmetic and household products. This review will discuss the
recent literature and the significance of this allergen to ACD (12).
Lyral is a fragrance that is present in many cosmetic products. It
has turned into an emergent allergen during the last years. In studies
carried out in other European countries, the prevalence of
sensitization to Lyral has been found to be 1.9-2.7 %, but it is
unknown the prevalence in Spain, as well as the need to include it or
not in the standard series of the Spanish Group of Contact Dermatitis
(GEIDC). All patients were patch-tested to Lyral with suspicion of
contact dermatitis of any origin who attended the Service between
April and May-2005. From a total of 170 patients included in this
study, 2 of them had a sensitization to Lyral (1.2 %). One of these
two patients had an axillae contact dermatitis caused by a deodorant
containing Lyral. The other patient was a masseur-woman with a
contact dermatitis on both hands, with periods of dissemination to
upper extremities and trunk, and who used several cosmetics
products for private reasons and during her job. In conclusion,
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although the sample of this study is quite small, the results allow to
suspect that Lyral is one of the main allergens, or even the most
important, in causing ACD to fragrances in the environment.
Therefore, Lyral should be included in the standard series of GEIDC,
either as independent allergen, or including it in a new mixture of
fragrances (13)

ASSESSMENT: some fragrances are known to be important

skin and potential airway sensitizers. These fragrance substances
have the potential to cause skin sensitization associated with the
development of ACD. Fragrances in particular are mostly used in
combination; combinations of fragrances can enhance sensitization
and elicitation.

References
1. Caress SM, Steinemann AC. Prevalence of fragrance sensitivity in the
American population. J Environ Health. 2009;71(7):46-50.
2. Thyssen JP, Linneberg A, Menné T, et al. The prevalence and morbidity of
sensitization to fragrance mix I in the general population. Br J Dermatol. 2009;
161(1):95-101.
3. Rastogi SC, Johansen JD, Bossi R. Selected important fragrance sensitizers in
perfumes - current exposures. Contact Dermatitis. 2007;56(4):201-4.
4. Rastogi SC, Johansen JD. Significant exposures to isoeugenol derivatives in
perfumes. Contact Dermatitis. 2008;58(5):278-81.
5. White IR, Johansen JD, Arnau EG, et al. Isoeugenol is an important contact
allergen: can it be safely replaced with isoeugenyl acetate? Contact Dermatitis.
1999;41(5):272-5.
6. Rastogi SC, Bossi R, Johansen JD, et al. Content of oak moss allergens
atranol and chloroatranol in perfumes and similar products. Contact Dermatitis.
2004;50(6):367-70.
7. Basketter D, Kimber I. Fragrance sensitisers: is inhalation an allergy risk?
Regul Toxicol Pharmacol. 2015;73(3):897-902.
8. Basketter DA, Lemoine S, McFadden JP. Skin sensitisation to fragrance
ingredients: is there a role for household cleaning/maintenance products? Eur J
Dermatol. 2015;25(1):7-13.
9. Uter W, Yazar K, Kratz EM, et al. Coupled exposure to ingredients of
cosmetic products: I. Fragrances. Contact Dermatitis. 2013;69(6):335-41.
10. Schnuch A, Oppel E, Oppel T, et al. Experimental inhalation of fragrance
allergens in predisposed subjects: effects on skin and airways. Br J Dermatol.
2010;162(3):598-606.
11. Frosch PJ, Johansen JD, Menné T, et al. Lyral is an important sensitizer in
patients sensitive to fragrances. Br J Dermatol. 1999;141(6):1076-83.
12. Militello G, James W. Lyral: a fragrance allergen. Dermatitis.
2005;16(1):41-4.
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13. Heras F, Díaz-Recuero JL, Cabello MJ, Conde-Salazar L. Sensitization to

Lyral. Actas Dermosifiliogr. 2006;97(6):374-8.

HEALTH EFFECTS
Fragranced consumer products-such as air fresheners, cleaning
supplies, and personal care products pervade society. This study
investigated the occurrence and types of adverse effects associated
with exposure to fragranced products in Australia, and opportunities
for prevention. Data were collected in June 2016 using an on-line
survey with a representative national sample (n=1,098). Overall, 33%
of Australians report health problems, such as migraine headaches
and asthma attacks, when exposed to fragranced products. Of these
health effects, more than half (17.1%) could be considered disabling
under the Australian Disability Discrimination Act. Additionally, 7.7%
of Australians have lost workdays or a job due to illness from
fragranced product exposure in the workplace, 16.4% reported
health problems when exposed to air fresheners or deodorizers,
15.3% from being in a room after it was cleaned with scented
products, and 16.7% would enter but then leave a business as quickly
as possible due to fragranced products. About twice as many
respondents would prefer that workplaces, health care facilities and
professionals, hotels, and airplanes were fragrance-free rather than
fragranced. While 73.7% were not aware that fragranced products,
even ones called green and organic, emitted hazardous air pollutants,
56.3% would not continue to use a product if they knew it did. This is
the study in Australia to assess the extent of adverse effects
associated with exposure to common fragranced products. It
provides compelling evidence for the importance and value of
reducing fragranced product exposure in order to reduce and prevent
adverse health effects and costs (1).
The influence of fragrances such as perfumes and room
fresheners on the psychophysiological activities of humans has been
known for a long time, and its significance is gradually increasing in
the medicinal and cosmetic industries. A fragrance consists of
volatile chemicals with a molecular weight of less than 300 Da that
humans perceive through the olfactory system. In humans, about
300 active olfactory receptor genes are devoted to detecting
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thousands of different fragrance molecules through a large family of

olfactory receptors of a diverse protein sequence. The sense of smell
plays an important role in the physiological effects of mood, stress,
and working capacity. Electrophysiological studies have revealed
that various fragrances affected spontaneous brain activities and
cognitive functions, which are measured by an
electroencephalograph (EEG). The EEG is a good temporal measure
of responses in the central nervous system and it provides
information about the physiological state of the brain both in health
and disease. The EEG power spectrum is classified into different
frequency bands such as delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13
Hz), beta (13-30 Hz) and gamma (30-50 Hz), and each band is
correlated with different features of brain states. A quantitative EEG
uses computer software to provide the topographic mapping of the
brain activity in frontal, temporal, parietal and occipital brain regions.
It is known that decreases of alpha and beta activities and increases
of delta and theta activities are associated with brain pathology and
general cognitive decline. In the last few decades, many scientific
studies were conducted to investigate the effect of inhalation of
aroma on human brain functions. The studies have suggested a
significant role for olfactory stimulation in the alteration of cognition,
mood, and social behavior. This review aims to evaluate the available
literature regarding the influence of fragrances on the
psychophysiological activities of humans with special reference to
EEG changes (2).

References
1. Steinemann A. Health and societal effects from exposure to fragranced
consumer products. Prev Med Rep. 2016;5:45-47. eCollection 2017 Mar.
2. Sowndhararajan K, Kim S. Influence of fragrances on human
psychophysiological activity: with special reference to human
electroencephalographic response. Sci Pharm. 2016;84(4):724-51.

ADVERSE REACTIONS
Fragranced consumer products, such as cleaning supplies, air
fresheners, and personal care products, are a primary source of
indoor air pollutants and personal exposure. Previous research
indicates that fragranced products can trigger adverse health effects,
with implications for workplaces and public places. This study
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examines the multiple dimensions of exposures related to fragranced

products and effects in the U.S. population. The study investigated
the prevalence and types of fragranced product exposures,
associated health effects, awareness of product emissions, and
preferences for fragrance-free policies and environments. Data were
collected using an online survey with a nationally representative
population (n=1,136) of adults in the U.S. Overall, 34.7% of the
population reported health problems, such as migraine headaches
and respiratory difficulties, when exposed to fragranced products.
Totally, 15.1% have lost workdays or a job due to fragranced product
exposure in the workplace. Also, 20.2 % would enter a business but
then leave as quickly as possible if they smell air fresheners or some
fragranced product. Over 50% of the population would prefer that
workplaces, health care facilities and professionals, hotels, and
airplanes were fragrance-free. While prior research found that
common fragranced products, even those called green and organic,
emitted hazardous air pollutants, more than two thirds of the
population were not aware of this, and over 60% would not continue
to use a fragranced product if they knew it emitted such pollutants.
Results from this study provide strong evidence that fragranced
products can trigger adverse health effects in the general population.
Reducing exposure to fragranced products, such as through
fragrance-free policies, can provide cost-effective and relatively
simple ways to reduce risks and improve air quality and health (1).
This article reviews side-effects of fragrance materials present in
cosmetics with emphasis on clinical aspects: epidemiology, types of
adverse reactions, clinical picture, diagnostic procedures, and the
sensitizers. Considering the ubiquitous occurrence of fragrance
materials, the risk of side-effects is small. In absolute numbers,
however, fragrance allergy is common, affecting approximately 1% of
the general population. Although a detailed profile of patients
sensitized to fragrances needs to be elucidated, common features of
contact allergy are: axillary dermatitis, dermatitis of the face,
including the eyelids, and neck, well-circumscribed patches in areas
of "dabbing-on" perfumes, wrists, behind the ears and aggravation of
hand eczema. Depending on the degree of sensitivity, the severity of
dermatitis may range from mild to severe with dissemination and
even erythroderma. Airborne or "connubial" contact dermatitis
should always be suspected. Other less frequent adverse reactions
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to fragrances are photocontact dermatitis, immediate contact

reactions and pigmentary changes. The fragrance mix, although
useful for the detection of sensitive patients, both causes false-
positive and false-negative reactions, and detects only 70% of
perfume-allergic patients. Therefore, future research should be
directed at increasing the sensitivity and the specificity of the mix.
Relevance is said to be established in 50-65% of positive reactions,
but accurate criteria are needed. Suggestions are made for large-
scale investigation of several fragrances on the basis of literature
data and frequency of use in cosmetics. The literature on adverse
reactions to balsam of Peru (an indicator for fragrance sensitivity),
essential oils (which currently appear to be used more in
aromatherapy than in perfumery) and on fragrances used as flavours
and spices in foods and beverages is not discussed in detail, but
pertinent side-effects data are tabulated and relevant literature is
provided (2).

ALLERGY. Contact allergy to fragrances is assessed mostly in

clinical populations of patients. Studies in the general population are
scarce and vary in their methodology across countries. The
prevalence of fragrance contact allergy in the European general
population and to assess the clinical relevance of positive patch test
reactions to different fragrances. In five European countries
(Germany, Italy, the Netherlands, Portugal and Sweden) a random
sample from the general population aged 18-74 years was drawn. In
total, 12 377 subjects were interviewed in this cross-sectional study
and a random sample (n=3,119) was patch tested using the TRUE
Test and Finn Chamber techniques. Patch test procedures were
harmonized by mandatory training before the study and monitoring
during the study. The highest prevalence for contact allergy of 2.6%
(95% confidence interval [CI] 2.1-3.2) was found for fragrance mix
(FM) I in petrolatum, with a high content of atranol and chloratranol,
followed by 1.9% (95% CI 1.5-2.4) for FM II in petrolatum. The
conservatively estimated prevalence of fragrance contact allergy was
1·9% (95% CI 1.5-2.5). This is defined as the existence of a positive
patch test to FM I or FM II; any of their individual materials;
Myroxylon pereirae; sesquiterpene lactones or 3- and 4-
hydroxyisohexyl 3-cyclohexene carboxaldehyde that show clinical
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relevance, defined conservatively as lifetime avoidance of scented

products and an itchy skin rash lasting > 3 days in a lifetime. Using
the reported lifetime prevalence of any contact dermatitis instead of
the lifetime prevalence of any itchy skin rash, the prevalence is 0.8%
(95% CI 0.5-1.2). The prevalence rates of contact allergy to
fragrances in women are about twice those in men (3).
Information on allergy to aromatic agents present in cosmetics
and products of household chemistry is reported. In the perfume
industry, about 3,000 aromas are used. Single products may contain
from 10 to 300 compounds. The problem of difficulties encountered
in the diagnosis of hypersensitivity to odors is addressed. The
mixture of 8 such products used in diagnostic screening is able to
detect allergy only in about 30% of patients who do not tolerate
cosmetics. Changing frequency of allergy to individual aromas is
discussed. It has been observed that cinnamon products are less
allergic than chemical compounds present in oak moss. Since the
1990s of the last century, allergy to a synthetic aromatic agent, Lyral
is the subject of interest in many research centers involved in studies
of contact allergy. Half the cosmetics present in European markets,
especially deodorants, after shave cosmetics; hand and body lotions
contain this agent. It induces positive reactions in about 10% of
patients allergic to aromatic agents. Detection of allergy to Lyral is
difficult as it is not included in the set of commercial allergens used
to diagnose hypersensitivity to aromatic agents (4).
An epidemiologic survey in the UK revealed that 23% of women
and 13.8% of men experience some sort of adverse reaction to a
personal care product over the course of a year. Although most of
these reactions may be due to subjective sensory irritation, various
studies reveal that up to 10% of dermatologic patients who are patch
tested are allergic to cosmetic products or their constituent
ingredients. Causative products include deodorants and perfumes,
skin care products, hair care products, and nail cosmetics. Allergic
contact dermatitis (ACD) mainly results from fragrance chemicals and
preservatives. Additional fragrance chemicals may need to be tested
in order to identify those patients 'missed' by the current FM; in
particular, hydroxy-isohexyl-3-cyclohexene carboxaldehyde (HMPPC
Lyral) has been singled out as an important sensitizing agent. The
increased usage of natural fragrances and botanic extracts can also
cause problems in their own right or through co-reactivity. The
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preservative methyldibromo glutaronitrile has been recognized as an

increasingly important sensitizer in Europe, which has led to the
recent recommendation that it should be prohibited from 'leave-on'
products until information on 'safe' consumer levels becomes
available. Other emerging allergens include UV filters,
tosylamide/formaldehyde resin, and nail acrylates. The diagnosis of
cosmetic allergy should be confirmed with patch testing; including
testing of 'whole' products, when necessary, and repeat open
application tests can be used to confirm the relevance of reactions in
cases of doubt (5).
The oxidized forms of the fragrance terpenes limonene and
linalool are known to cause allergic contact dermatitis. Insignificant
rates of contact allergy to these fragrances have been reported in
European studies and in a recent worldwide study. Patch testing to
oxidized terpenes is not routinely carried out either in the U.K. or in
other centres internationally. The objective of this study was to
investigate the prevalence of contact allergy to oxidized limonene
and linaloolin the U.K. Between 1 August 2011 and 31 December
2012, 4,731 consecutive patients in 13 U.K. dermatology
departments were tested for hydroperoxides of limonene 0.3% pet.,
hydroperoxides of linalool 1.0% pet., stabilized limonene 10.0% pet.,
and stabilized linalool 10.0% pet. Doubtful (?+) and equivocal (±)
reactions were grouped together as irritant reactions. Two hundred
and thirty-seven patients (5.0%) had a positive patch test reaction to
hydroperoxides of limonene 0.3% pet and 281 (5.9%) to
hydroperoxides of linalool 1.0% pet. Irritant reactions to one or both
oxidized terpenes were found in 242 patients (7.3%). Eleven patients
(0.2%) had a positive patch test reaction to the stabilized terpenes
alone. In conclusion, this large, multicenter U.K. audit shows a
significant rate of allergy to the hydroperoxides of limonene and
linalool plus a high rate of irritant reactions. Testing to the oxidized
forms alone captures the majority (97.0%; 411 of 422) of positive
reactions; testing to nonoxidized terpenes appears to be less useful.
In conclusion, the hydroperoxides of limonene and linalool should be
added to an extended baseline patch test series (6).
The incidence of allergy induced by fragrances, leading mostly to
the development of contact dermatitis and urticaria chronica, has
been growing in a large number of countries. In general, allergy is of
non-occupational nature, however, it can also have traits of
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occupational exposure. The FM is used in screening for allergy to

aromas, but it frequently produces false positive or false negative
results of the test. The aim of the study was to assess whether the
FM is suitable for detecting allergy to aromas in persons with
suspected occupational allergy and also to analyze types of allergy to
separate fragrances. In a group of 1937 patients diagnosed in the
Nofer Institute of Occupational Medicine in Lódź, the incidence of
allergy to FM was assessed. They underwent dermatological
examinations and tests with use of the European standard kit
(Chemotechnique Diagnostics, Malmö, Sweden) in the years 2000-
2005. In addition, in the group of patients with positive tests, the
type of allergy to individual aromas was analyzed using fragrance
series (Chemotechnique Diagnostics, Malmö, Sweden). The positive
reaction to FM was found in 99 (5.1%) patients (5.2% women and
4.9% men). In 57.6% of patients, allergy to balsam of Peru was also
observed. Allergy to at least one aroma was diagnosed in 82 (72%)
persons tested with an expanded fragrance series. In the remaining
23 (28%) patients, patch tests proved to be false positive. In the
latter group, 17 patients showed negative results of the test to
balsam of Peru. In the study group, 65% of patients reacted to 1, 2 or
3 and 36% to more aromas. The following allergens sensitized most
frequently: cynnamic alcohol, hydroxycitronellal, cinnamic aldehyde,
isoeugenol, eugenol, Ylang-Ylang oil, oakmoss absolute, and jasmine.
ACD was diagnosed in 69.7%, urticaria chronica in 5.1% of patients,
atopic dermatitis in 4%, whereas in 21.2% no skin lesions were
observed. In conclusion, the results of the study confirmed
observations of other authors that the usefulness of FM in the
diagnosis of allergy to aromas is limited (a high number of false
positive results of skin tests). A combined reaction to FM and balsam
of Peru is helpful in diagnosis in persons whom a complete allergic
diagnosis cannot be performed. Less frequent hypersensitivity was
found to oakmoss absolute and more frequent to cinnamic aldehyde
and alcohol, hydroxycitronellal, eugenol, isoeugenol in Lódź than in
studies reported by other authors (7).
Assessment of the value of patch testing patients' own perfumes,
eau de toilette, deodorants and shaving lotions with regard to
diagnosing contact allergy to fragrances, and an analysis of the
spectrum of concurrent patch test reactions to single fragrance
allergens. Data of the Information Network of Departments of
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Dermatology regarding patch test results with above products

brought in by the patient, considered as possible cause of contact
dermatitis, were retrospectively analyzed. Between 1998 and 2002,
1,468 patients were patch tested with 2,557 single products
(deodorants, n=1,094; eau de toilette, n=598; perfume, n=530; and
pre- or after-shave, n=325; remainder not classifiable), mostly 'as is'.
Positive reactions were observed in 129 patients (to 191 products).
In 58 of these patients, no further patch test reactions to the
fragrance mix (FM-I), Myroxylon pereirae resin (balsam of Peru) or (4-
hydroxy-4-methyl-pentyl)-3-cyclohexencarboxaldehyde (e.g. Lyral(R))
were found. A strong association between contact sensitivity to the
above commercial allergens and positive reactions to products was
observed. Some single compounds such as ylang-ylang oil, propolis
and especially oak moss absolute are important allergens in the
'perfume-positive' subgroup, but less in a subgroup positive to own
deodorants. Patch testing this scope of products, brought in by the
patient, can be regarded as a simple, safe and effective method to
diagnose clinically relevant contact sensitization - the more so, as the
composition of such products is ever-changing, and the sensitivity of
established 'screening allergens' is thus insufficient (8).
Conducting a sound skin sensitization risk assessment prior to the
introduction of new ingredients and products into the market place is
essential. The process by which low-molecular-weight chemicals
induce and elicit skin sensitization is dependent on many factors,
including the ability of the chemical to penetrate the skin, react with
protein, and trigger a cell-mediated immune response. Based on the
chemical, cellular and molecular understanding of ACD, it is possible
to carry out a quantitative risk assessment. Specifically, by estimating
the exposure to the allergen and its allergenic potency, it is feasible
to assess quantitatively the sensitization risk of an ingredient in a
particular product type. This paper focuses on applying exposure-
based risk assessment tools to understanding fragrance allergy for 2
hypothetical products containing the fragrance allergen cinnamic
aldehyde. The risk assessment process predicts that an eau de
toilette leave-on product containing 1,000 ppm or more cinnamic
aldehyde would pose an unacceptable risk of induction of skin
sensitization, while a shampoo, containing the same level of cinnamic
aldehyde, would pose an acceptable risk of induction of skin
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sensitization, based on limited exposure to the ingredient from a

rinse-off product application (9).
This study (10) has been performed to evaluate the efficacy of FM
as a screen for fragrance allergy. Patients were included if they had
had positive allergic reactions to FM, to 1 of the 8 ingredients of FM,
to 1 of 14 other fragrance materials, or to their own perfume.
Totally, patients were studied. There were 65 women and 23 men (in
3, their sex was not recorded) allergic to FM on patch testing. The
mean (+/-SD) age was 48.4+/-18.6 years; 22 patients gave a past
history of atopic eczema. Dermatitis of the hands (31%) and face
(26%) were the most common presenting complaints; 85 patients
(93%) had a positive allergic patch test reaction to FM; 22 of the 40
tested to the extended fragrance series were positive to other
perfumes as well, and of these, there were 14 reactions (in 9
patients) to allergens not in the FM. In addition, 6 patients were
positive only to separately tested fragrance constituents and not to
the FM. In conclusion, FM is an accurate screen for fragrance contact
sensitivity. However, patch testing to an extended series is needed if
there is clinical suspicion of perfume allergy, as otherwise about 7%
of patients allergic to fragrances will be missed (10).
The aim of the study was to investigate the elicitation potential of
perfumes from 17 commonly sold lower-price cosmetic products.
Eight of the perfumes were from stay-on cosmetics and 9 were from
wash-off cosmetics. Each perfume was tested in 500 consecutive
eczema patients, who also were tested with the European standard
patch test series. 4.2% reacted to 1 or more of the wash-off product
perfumes and 3.2% to 1 or more of the stay-on product perfumes.
Concordant positive reactions between the FM and the product
perfumes were found in 81.3% of positive reactions to the stay-on
product perfumes and in 52.4% of the reactions to the wash-off
product perfumes. Compared to the FM alone, only 1 additional case
of contact allergy to the product perfumes was detected by balsam of
Peru. Chemical analysis revealed that between 1 and 5 of the
chemically-defined constituents of the FM were present in all of the
product perfumes. Geraniol was found in 12 of the 17 perfumes and
was most often detected. The concentration of the target fragrance
materials ranged from 0.005%-1.35 w/v%. It is concluded that the
allergenic constituents of the FM are impossible to avoid if perfumed
cosmetics are used. Patients suspected of perfume allergy need to
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be tested with their own perfumed products, as far from all cases of
perfume allergy are detected by the FM and/or balsam of Peru in the
European standard patch test series (11).
Allergy to fragrance is the most common cause of cosmetic
contact dermatitis and therefore constitutes a significant clinical
problem. The widespread use of fragranced materials in skin care
and household products is probably the most important reason for
the high incidence of fragrance sensitization. This report will
summarize the history of fragrance, review how to detect and
evaluate fragrance allergy, discuss the problems inherent in patch
testing with the FM and its constituents, describe systemic contact
dermatitis from ingestion of certain flavors, and give suggestions for
fragrance-sensitive patients. In conclusion, the use of FM in patch
testing has been invaluable in detecting fragrance allergy. Continued
investigation into positive patch test responses to fragrance in
scented products is essential in helping to identify new fragrance
allergens. Additionally, more cooperation is necessary between
industry and dermatologists in assisting patients to avoid proven
allergens (12).

CONTACT DERMATITIS. Fragrances are a common cause of

allergic contact dermatitis (ACD) in Europe and North America. They
can affect individuals at any age and elicit a spectrum of reactions
from contact urticarial to systemic contact dermatitis. Growing
recognition of the widespread use of fragrances in modern society
has fueled attempts to prevent sensitization through improved
allergen identification, labeling, and consumer education. This
review provides an overview and update on fragrance allergy (13).
Fragrances are the first or second most common cause of contact
allergy in dermatitis patients. The aim of this study was to identify
risk products for fragrance contact allergy. The design was a case-
control study with a case group of 78 fragrance-mix (FM)-positive
eczema patients and two control groups, one consisting of 1,279
subjects selected as a random sample of the general population and
the other consisting of 806 FM-negative eczema patients. The
identification of risk products was based on the patients' histories of
rash to scented products. Analysis of the associations between first-
time rash caused by different specified product categories and FM
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sensitivity was performed using logistic regression. First-time rash

caused by deodorant sprays and/or perfumes were related to
fragrance contact allergy in a comparison with both control groups.
The risk (odds ratio) of being diagnosed as fragrance allergic was 2.3
to 2.9 greater in cases of a history of first-time rash to deodorant
sprays and 3.3 to 3.4 greater in cases of a history of rash to perfumes
than if no such history were present. The rash to cleansing agents,
deodorant sticks, or hand lotions was also statistically significant but
only in comparison with one of the control groups. In conclusion,
safety evaluation of fragrance materials used in perfumes and
deodorant sprays should be performed with special attention (14).
Fragrance materials are not only present in products primarily
used for their scent such as perfume, eau de toilette, deodorant and
aftershave, but also in cosmetics, toiletries, household products and
industrial materials. Of the general population, approximately one
percent is allergic to fragrance materials, men nearly as frequent as
women. Of patients consulting the dermatologist because of
dermatitis, 6-11% has a positive patch test to the FM. ACD due to
fragrances usually consists of erythema and desquamation, often
localized in the neck, behind the ears, in the arm-pits or around the
eyes. It can worsen pre-existing dermatoses such as hand eczema,
atopic dermatitis, perianal dermatitis or vulvar dermatitis. The
diagnosis of contact allergy to fragrances is made by epicutaneous
tests with the European standard series (including some markers for
fragrance sensitivity: the FM, balsam of Peru and colophony) and the
patient's own contact materials. A positive patch test reaction must
be followed by evaluation of its relevance. Advice to the patient is
directed towards avoidance of fragranced products, if possible, and
explanation of how use tests can identify fragranced products which
can be used without ill effects (15).
In published reports from Europe, 3- and 4-(4-hydroxy-4-
methylpentyl) cyclohexene-1-carboxaldehyde (HMPCC) (Lyral) has
been described as a common cause of ACD. In Europe, the rates of
reaction to HMPCC among patients undergoing patch testing for
suspected ACD have varied from 1.2 to 17.0%, depending on the
country. Data on the incidence of sensitivity to HMPCC among North
Americans with suspected ACD have not been reported. The goals of
this study were 1] to assess the incidence of delayed-type
hypersensitivity reactions to HMPCC among patients undergoing
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patch testing for evaluation of eczematous dermatitis at six centers

throughout North America; 2] to determine the most appropriate
concentration of HMPCC to use in performing patch tests; and 3] to
compare and contrast the incidence rates for HMPCC hypersensitivity
to those for other fragrance materials screened with the North
American Contact Dermatitis Group (NACDG) screening tray, which
includes FM, Myroxilon pereirae (balsam of Peru), cinnamic
aldehyde, ylang ylang oil, jasmine absolute, and tea tree oil. This
report represents the prospective multicenter data on patients
tested with the fragrance-related allergens on the NACDG standard
screening tray and with HMPCC at 5%, 1.5%, and 0.5% concentrations
in petrolatum. Data from 1,603 patients evaluated at five U.S. sites
and one Canadian site were analyzed. Most patients (87.8%) were
Caucasian. The majority (67%) was women, and 26.2% had a history
consistent with atopic dermatitis. The patients ranged in age from 1
to 88 years, and the mean +/- standard deviation was 46.3 +/- 16.5
years. Myroxilon pereirae (balsam of Peru) and FM were the most
frequent patch-test-positive fragrance allergens (6.6% and 5.9%,
respectively). Cinnamic aldehyde (1.7%), ylang ylang oil (0.6%),
jasmine absolute (0.4%), HMPCC (0.4% for 5% HMPCC, 0.3% for 1.5%
HMPCC, and 0.2% for 0.5% HMPCC), and tea tree oil (0.3%) less
frequently yielded positive reactions. Men were more likely than
women to be allergic to cinnamic aldehyde. Women were more
likely than men to be allergic to jasmine absolute. Atopic patients
were no more likely to react to fragrance materials than were
nonatopic patients. Patients who reacted to jasmine absolute tended
to be older than the general population whereas those who reacted
to tea tree oil tended to be younger than the general population.
There were no other demographic differences between patients who
reacted to a given fragrance material and the entire population
studied. Testing with FM and balsam of Peru failed to identify the
majority of patients in this study who were found to be sensitized to
jasmine absolute, HMPCC, or tea tree oil. In conclusion, HMPCC is an
uncommon allergen in the North American population. Testing with
5% HMPCC in petrolatum is recommended for those patients
suspected of having a fragrance allergy (16).
The frequency of contact allergy to the 10 best-selling women's
perfumes was studied in 335 consecutive female eczema patients by
patch testing. The diagnostic ability of the FM, in relation to these
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products, was evaluated. Of eczema patients, 6.9% had a positive

patch test to one or more of the perfumes, and 56.5% of these had a
concurrent positive reaction to the FM. Hence, testing with the
patients' own cosmetics is a significant part of diagnosing perfume
allergy. The clinical relevance of the patch-test reactions to the
commercial perfumes was equal to that of the FM, as judged from
the patient's history and use testing with one of the perfumes. At
least three of the chemically defined sensitizers in the FM were
detected in all the perfumes by gas chromatography-mass
spectrometry, which indicates that the FM is a good imitation of
actual exposure (17).
The purpose of this study was to determine the frequency of
responses to selected fragrance materials in patients who were
fragrance sensitive. Totally, 178 patients were evaluated in 8 centers
worldwide with a FM and 20 other fragrance materials. Reaction to
the FM occurred in 78.7% of the subjects. Substances reacting at a
rate of 2% or higher included jasmine absolute, geranium oil
bourbon, l-citronellol, spearmint oil, 1,3,4,6,7,8-hexahydro-
4,6,6,7,8,8-hexamethyl cyclopenta-gamma-2-benzopyran, omega-6-
hexadecenlactone, dimethyltetrahydro benzaldehyde (isomer
mixture), and alpha-amylcinnamaldehyde. The chemicals should be
evaluated to corroborate their allergenicity. New fragrance allergens
are sought to extend the diagnostic capability of the FM (18).
The purpose of this study was to determine the frequency of
responses to selected fragrance materials in patients who were
fragrance sensitive. Totally, 218 fragrance sensitive subjects were
evaluated in eight centers worldwide with a FM and 17 less well-
studied fragrance materials. Reaction to the FM occurred in 76% of
the subjects. The FM detected all reactions to nerol and
hydroxycitronellol and 93% of the reactions to clove bud oil. Ten
fragrance materials were not detected by the FM and deserve further
study: benzenepropanol, beta, beta, 3-trimethyl, hexyl-salicylate, dl-
citronellol, synthetic ylang ylang oil, benzyl mixture, cyclohexyl-
acetate, eugenyl methyl ether, isoeugenyl methyl ether, 3-phenyl-1-
propanol, and 3, 7-dimethyl-7-methoxyoctan-2-ol (19).
The aim of this study was to determine the prevalence of
responses to selected fragrance materials in patients with suspect
fragrance allergy and to evaluate risk factors and associations with
such responses. The validity of using specific fragrance ingredients
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versus a mixture of fragrances was evaluated in terms of predicting

allergy to different fragrance ingredients. One hundred sixty-seven
subjects were evaluated in seven centers worldwide with a FM, the
eight ingredients in the fragrance mixture, six other well-known
fragrance allergens, balsam of Peru, and 15 lesser studied fragrance
materials. The age of the patients was 44.9 +/- 17.5 years (mean +/-
SD). More than 85% were women. A relatively high proportion gave
a past history of atopic disease. Facial eruptions (40%) and hand
involvement (26.7%) were the most common topographic sites. All
but 4 of the 35 fragrance materials produced a positive response in >
1%. A reaction to FM occurred in 47.3%. Seven of the 34 ingredients
tested produced an allergic response in more than 10% of those
tested. Men were more likely than women to exhibit a positive
response to five fragrance ingredients. White persons were more
likely to react to perfume mix (52.8% versus 25.3%) and certain
ingredients in the mix than Asian persons. Allergy to benzyl salicylate
was more common in Japan than in Europe or the United States. In
conclusion, the age at which patients with perfume allergy present
for evaluation is similar to that of other contactants. Atopic
individuals may be overrepresented in this group of patients. Face
involvement is likely. White persons are more likely to react to FM,
whereas in Asian patients benzyl salicylate was a more frequent
allergen. FM corrected with 85.6% of positive responses to fragrance
ingredients. The addition of ylang ylang oil, narcissus oil, and
sandalwood oil to FM would be expected to pick up 94.2% with
positive responses to fragrance materials; adding balsam of Peru
increases this to 96% (20).
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 FM. 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 is sensitized to
ingredients of the FM. 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 FM are
present in 15-100% of cosmetic products, including deodorants and
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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 labeled 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 2,500 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 FM 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 (21).
The prevalence of contact allergy to fragrance ingredients
increased during the last part of the 20th century with the
consequence that a substantial number of individuals are at risk of
experiencing ACD if they have a sufficient degree of skin exposure to
the chemical to which they have become sensitized. Such exposure
does not necessarily have to arise from the type of source that
originally induced the sensitization. Some sources of exposure are
associated with risk of elicitation of ACD, but the role of fragrance
deposited on fabrics, for example as a result of laundry processes,
also can be questioned. In this article, firstly, the risk of the induction
of fragrance-related ACD from exposure to fragrance via fabric is
considered. Using a quantitative risk-assessment approach, the risk
appears to be extremely low. There is the possibility that fragrance
residues on laundered fabrics might elicit reactions in those already
sensitized by a different route. Clinically, clothing pattern dermatitis
associated with fragrance allergy is almost never observed, although
this could be investigated clinically by exposing sensitized individuals
to the relevant fragrance allergen (22).
The case is reported of a 28-year-old man who developed ACD
from 2 synthetic fragrance ingredients, Lyral (3- and 4-(4-hydroxy-4-
methylpentyl)-3-cyclohexene-1-aldehyde) and acetyl cedrene, in
separate underarm deodorant preparations. There are implications
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of the patient's negative patch test reactions to the European

standard series (Trolab) and cosmetics and fragrance series (both
Chemotechnique Diagnostics). The importance is stressed of patch
testing with the patient's own preparations when cosmetic dermatitis
is suspected, and reporting offending fragrance ingredients, with a
view possibly to updating the European standard series and
commercially available cosmetics and fragrance series (23).
The currently used FM in the European baseline patch test series
(baseline series) fails to detect a substantial number of clinically
relevant fragrance allergies. The main objective of this study was to
investigate whether it is justified to include hydroxyisohexyl 3-
cyclohexene carboxaldehyde (Lyral) and FM 2 containing
hydroxyisohexyl 3-cyclohexene carboxaldehyde, citral, farnesol,
coumarin, citronellol, and alpha-hexyl cinnamal in the European
baseline patch test series. Survey of the literature on reported
frequencies of contact allergy and ACD from FM 2 and
hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral) as well as
reported results of experimental provocation test. FM 2 has been
demonstrated to be a useful additional marker of fragrance allergy
with contact allergy rates up to 5% when included in various national
baseline patch test series. Of the fragrance substances present in FM
2, hydroxyisohexyl 3-cyclohexene carboxaldehyde is the most
common sensitizer. Contact allergy rates between 1.5% and 3% have
been reported for hydroxyisohexyl 3-cyclohexene carboxaldehyde in
petrolatum (pet.) at 5% from various European centers when tested
in consecutive dermatitis patients. In conclusion, from 2008, pet.
preparations of FM 2 at 14% w/w (5.6 mg/cm(2)) and
hydroxyisohexyl 3-cyclohexene carboxaldehyde at 5% w/w (2.0
mg/cm(2)) are recommended for inclusion in the baseline series.
With the Finn Chamber technique, a dose of 20 mg pet. Preparation
is recommended. Whenever there is a positive reaction to FM 2,
additional patch testing with the 6 ingredients, 5 if there are
simultaneous positive reactions to hydroxyisohexyl 3-cyclohexene
carboxaldehyde and FM 2, is recommended (24).
The aim of the present study was to investigate the relationship
between patients' own recognition of skin problems using consumer
products and the results of patch testing with markers of fragrance
sensitization. Eight hundred and eighty-four consecutive eczema
patients, 18-69 years of age, filled in a questionnaire prior to patch
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testing with the European standard series. The questionnaire

contained questions about skin symptoms from the use of scented
and unscented products as well as skin reactions from contact with
spices, flowers and citrus fruits that could indicate fragrance
sensitivity. A highly significant association was found between
reporting a history of visible skin symptoms from using scented
products and a positive patch test to the FM, whereas no such
relationship could be established to the Peru balsam in univariate or
multivariate analysis. The results suggest that the role of Peru
balsam in detecting relevant fragrance contact allergy is limited,
while most FM-positive patients are aware that the use of scented
products may cause skin problems (25).
Among men, the most frequent contact allergens are perfumes
(FM and balsam of Peru). Considering that the main cause of nickel
allergy is ear-piercing, shaving with a razor blade might be the cause
of perfume contact allergy, by creating small wounds that increase
the penetration of applied perfume substances derived from soaps,
shaving foams and after-shave lotions. Nineteen males with contact
allergy to FM and/or to balsam of Peru were interviewed about their
shaving habits by letter. 17 responded (89%), of whom 12 (71%) had
been using razor blades continuously for a period of at least 1 year.
At the clinic, the frequency of razor blade usage was found to be 45%
in patch tested men without perfume contact allergy. When
comparing the frequencies of razor blade usage among patch tested
men with and without perfume contact allergy, there was a
statistically significant over-representation (p=0.047) among those
with perfume allergy. The risk of perfume allergy was 2.9 (odds ratio)
when using razor blades (26).

ECZEMA. Because hand eczema and fragrance allergy are

common both among patients and in the general population,
simultaneous occurrence by chance must be expected. Fragrances
are ubiquitous and a part of many domestic and occupational
products intended for hand exposure. The present review is based
on a systematic literature research using both a manual and a
Medline based search. The search identified 39 studies, including
epidemiological patch test studies, general population patch test
studies, case studies, and studies of occupational groups. The
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published data indicate a possible association between fragrance

allergy and hand eczema. In future studies, a more detailed exposure
assessment is needed, combined with patch test studies among
patients with hand eczema tested with relevant fragrance allergens,
as well as experimental control exposure studies to specific fragrance
allergens on the hands. As exposures to fragrances on the hands are
often simultaneous exposures to irritants, this combined exposure
approach needs to be considered (27).

MUCOSAL SYMPTOMS. Exposure to perfume and fragrance

products may, in some individuals, cause symptoms from the eyes
and airways. The localization, character and risk factors of such
symptoms in the general population are unknown. The objective of
this study was to investigate both the localization and character of
symptoms from the eyes and airways elicited by fragrance products,
and the associations between such symptoms and skin prick test
reactivity (atopy), methacholine bronchial hyper-reactivity (BHR),
allergic rhinitis and asthma. A questionnaire on mucosal symptoms
elicited by fragrance products was posted to 1,189 persons who had
participated in a Danish population-based study of allergic diseases in
1997/1998. The study included measurement of BHR, atopy, forced
expiratory volume in 1 s (FEV1), and serum eosinophilic cationic
protein (serum ECP). The response rate was 79.6%. Symptoms from
the eyes or airways elicited by fragrance products were reported by
42%. BHR (adjusted odds ratio 2.3, 95% confidence interval 1.5-3.5)
was independently associated with symptoms from the eyes and
airways elicited by fragrance products. There were insignificant
associations between these symptoms and atopy, FEV1 or serum
ECP. In conclusion, mucosal symptoms from the eyes and airways
were common in this population. BHR was a significant and
independent predictor of these symptoms. The lack of association
with atopy suggested that IgE-mediated allergic mechanisms do not
play a major role in the development of these symptoms (28).
Many asthmatics report worsening of symptoms following
exposure to odors and sensory irritants commonly found in
household and cosmetic products. Despite this, little evidence exists
to confirm the degree to which such subjective reports are correlated
with localized, objective changes in the upper or lower airways
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following a fragranced product exposure. Subjective symptom

reports were compared to objective measures in mild asthmatics,
moderate asthmatics and non-asthmatics following exposure to one
of two fragranced household aerosol mixtures and a clean air control
condition to determine if asthmatics reported greater subjective
symptoms of nasal congestion or exhibited objective measures of
elevated ocular irritation and nasal congestion following exposure
than did healthy controls. Measures of nasal mucosal swelling, using
acoustic rhinometry, and photographic assessments of ocular
hyperemia, using macro-photography, were taken before exposure,
immediately after an initial 5-min exposure and again following a 30-
min exposure to either of two, fragranced aerosol products and a
clean air control. Self-reports of nasal patency at each time-point
were also obtained. Although moderate asthmatics tended to report
more nasal congestion following fragranced product exposure than
did non-asthmatics, no exposure-related changes in ocular redness or
nasal mucosal swelling were observed among the three groups.
Spirometry readings also failed to show evidence of any exposure-
related changes in pulmonary function. In conclusion, despite claims
that exposure to fragranced products may trigger ocular and
respiratory symptoms among asthmatics, evidence was not found
that 30 min of exposure to one of two fragranced aerosols elicited
objective adverse effects in the ocular or nasal mucosa of mild and
moderate asthmatics. While physiological mechanisms of fragrance
impact may yet be responsible for some of the adverse reports
among asthmatics following fragrance exposure, such reports may
also reflect a non-physiological locus of symptom perception
triggered by other sensory cues (29).

RESPIRATORY SYSTEM. Respiratory symptoms from

environmental perfume exposure are main complaints in patients
with multiple chemical sensitivities and often coincide with asthma
and or eczema. In this population-based twin study, the heritability
of respiratory symptoms related to perfume was estimated and if co-
occurrences of the symptoms in asthma, atopic dermatitis, hand
eczema or contact allergy were influenced by environmental or
genetic factors common with these diseases were evaluated. In
total, 4,128 twin individuals (82%) responded to a questionnaire. The
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heritability of respiratory symptoms related to perfume was 0.35,

95% CI 0.14-0.54. Significant associations (p<0.05) between
perfume-related respiratory symptoms and asthma, atopic
dermatitis, hand eczema or contact allergy are not attributable to
shared genetic or shared environmental/familial factors, except
possibly for atopic dermatitis where genetic pleiotropy with
respiratory symptoms to perfumes suggested by an estimated
genetic correlation of 0.39, 95% CI 0.09-0.72 (30).
Exposure to volatile fragrances is commonplace and may be
related to various eye and airway symptoms. Skin exposure to
fragrances is known to cause perfume contact allergy and eczema,
but it is unknown whether eye or airway symptoms elicited by
fragrance products are associated with contact allergy or eczema. If
eye and airway symptoms elicited by fragrance products are
associated with perfume contact allergy or hand eczema was
investigated in a population-based sample. A questionnaire on eye
and airway symptoms elicited by fragrance products was mailed to
1,189 individuals who had recently participated in a Danish
population-based study of allergic diseases. Results from the
questionnaire about localization and character of the symptoms were
compared with data on patch testing and 1-year prevalence of hand
eczema collected during the health examination. Positive,
independent and significant (p<0.05) associations were found
between eye and airway symptoms elicited by fragrance products
and perfume contact allergy (adjusted odds ratios 2.0-3.7) and hand
eczema (adjusted odds ratios 1.6-2.6). Similar and consistent results
were found regarding severity of the symptoms. No associations
were found between nickel contact allergy and the symptoms.
Female sex and psychological vulnerability were independently
associated with eye and airway symptoms elicited by fragrance
products, but adjustment in multivariate analysis did not change the
results regarding perfume contact allergy and hand eczema. In
conclusion, individuals with perfume contact allergy and/or hand
eczema, as opposed to those without, have more frequent and more
severe eye or airway symptoms after exposure to volatile fragrance
products. Having hand eczema has the greatest impact on reporting
eye and airway symptoms elicited by fragrance products (31).
Production employees in the UK fragrance industry are exposed to
large numbers of chemical substances and mixtures. There is a lack
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of published literature describing the effects of occupational

respiratory exposure in this industry. Whether occupational
respiratory exposure to chemicals in the UK fragrance industry is
linked to a statistically significant change in lung function as
measured using spirometry was investigated. A multi-site cross-
sectional study in which five UK companies took part, comprised an
exposed group (fragrance production and associated functions) and a
control group (non-exposed industry employees, e.g. office staff).
Spirometric measurements (forced expiratory volume in 1 second,
forced vital capacity and peak expiratory flow) were taken pre- and
post-shift. Participants provided information on potential
confounding factors (smoking, history of respiratory problems and
body mass index). Post-shift measurements were compared
between groups, using analysis of covariance to adjust for the
baseline pre-shift measurements. A total of 112 subjects
participated: 60 in the exposed group and 52 in control group
(response rate 33 and 24%, respectively). Adjusted mean differences
in post-shift spirometric measurements between exposed and
control groups were statistically insignificant. In conclusion,
insignificant effects were observed on the spirometric performance
of the study population (32).
Although the flavor and fragrance industry is about 150 years old,
the use of synthetic materials started more than 100 years ago, and
the awareness of the respiratory hazard presented by some flavoring
substances emerged only recently. In 2001, the U.S. National
Institute of Occupational Safety and Health (NIOSH) identified for the
first time inhalation exposure to flavoring substances in the
workplace as a possible occupational hazard. As a consequence,
manufacturers must comply with a variety of workplace safety
requirements, and management has to ensure the improvement of
health and safety of the employees exposed to hazardous volatile
organic compounds. In this sensitive context, MANE opened its
facilities to an intensive measuring campaign with the objective to
better estimate the real level of hazardous respiratory exposure of
workers. In this study, exposure to 27 hazardous volatile substances
were measured during several types of handling operations
(weighing-mixing, packaging, and reconditioning-transferring), 430
measurement results were generated, and were exploited to propose
an improved model derived from the well-known ECETOC-TRA
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model. The quantification of volatile substances in the working

atmosphere involved three main steps: adsorption of the chemicals
on a solid support, thermal desorption, followed by analysis by gas
chromatography-mass spectrometry. This approach was used to
examine experimental measures done in various manufacturing
workplaces and to define correction factors to reflect more
accurately working conditions and habits. Four correction factors
were adjusted in the ECETOC-TRA to integrate important exposure
variation factors: exposure duration, percentage of the substance in
the composition, presence of collective protective equipment and
wearing of personal protective equipment. Verification of the
validity of the model is based on the comparison of the values
obtained after adaptation of the ECETOC-TRA model, according to
various exposure scenarios, with the experimental values measured
under real conditions. After examination of the predicted results,
98% of the values obtained with the proposed new model were
above the experimental values measured in real conditions. This
must be compared with the results of the classical ECETOC-TRA
system, which generates only 37% of overestimated values. As the
values generated by the new model intended to help decision-
makers of the industry to implement adapted protective action and
information, and considering the high variability of the working
environments, it was of the utmost importance not to underestimate
the exposure level. The proposed correction factors have been
designed to achieve this goal. The present method is proposed as an
improved monitoring tool to improve respiratory health and safety in
the flavor and fragrance manufacturing facilities (33).
Fragrance chemicals are used in a large array of products.
Workers may be exposed to these chemicals in the workplace directly
when used as air fresheners, or indirectly in personal care products
used by coworkers or others. This study characterizes work-related
asthma (WRA) cases associated with fragrance exposures in
California workplaces from 1993 through 2012. The California Work-
Related Asthma Prevention Program's surveillance database was
used to identify individuals with physician-diagnosed WRA associated
with the use of air fresheners and scented personal care products
(perfumes, colognes, etc.). Perfume was the ninth most common
exposure identified from 1993 through 2012. A total of 270 WRA
cases associated with fragrance exposure were reported during this
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period, representing 3.8% of all confirmed cases. These 270 cases

included 242 associated with perfume or cologne, 32 associated with
air freshener, and 4 associated with both. Similar to non-fragrance
cases, nearly a quarter of fragrance-associated cases were classified
as new-onset asthma. Fragrance-associated cases were significantly
more likely to be in office, health, and education jobs than non-
fragrance-associated cases. When compared to non-fragrance cases,
fragrance cases were significantly more likely to be female (94% vs.
62%) and be classified as having work-aggravated asthma (38% vs.
20%), yet had similar outcomes compared with cases associated with
other exposures. In conclusion, fragrance use in the workplace is
associated with WRA. Prevention methods include employee
education, enforced fragrance-free policies, well-designed ventilation
systems, and appropriate building maintenance (34).
Fragrances and strong odors have been characterized as putative
triggers that may exacerbate asthma symptoms and many asthmatics
readily avoid odors and fragranced products. However, the
mechanism by which exposure to pure, non-irritating odorants can
elicit an adverse reaction in asthmatic patients is still unclear and
may involve both physiological and psychological processes. The aim
of this study was to investigate how beliefs about an odor's
relationship to asthmatic symptoms could affect the physiological
and psychological responses of asthmatics. Asthmatics classified as
'moderate-persistent', according to NIH criteria, were exposed for 15
min to a fragrance which was described either as eliciting or
alleviating asthma symptoms. During exposure, participants were
asked to rate odor intensity, perceived irritation and subjective
annoyance while physiological parameters such as
electrocardiogram, respiratory rate, and end tidal carbon dioxide
(etCO₂) were recorded. Before, immediately after, and at 2 and 24h
post-exposure, participants were required to subjectively assess their
asthma symptom status using a standardized questionnaire. Asthma
status was measured at each of those time points using objective
parameters of broncho-constriction (spirometry) and measures of
airway inflammation (exhaled nitric oxide, FeNO). Manipulations of
perceived risk altered both the quality ratings of the fragrance as well
as the reported levels of asthma symptoms. Perceived risk
modulated the inflammatory airway response. In conclusion,
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expectations elicited by smelling a perceived harmful odor may affect

airway physiology and impact asthma exacerbations (35).
Many household products contain fragrances. Little is known
about exposure to fragrances on human health, particularly within
the airways. Therefore, this study aimed to evaluate how common
household fragrance products (i.e. air fresheners, cleaning products)
affect people with asthma, who frequently report sensitivity to these
products. Many of these products have volatile organic compounds
or semi-volatile organic compounds. The study evaluated nine
fragrance materials in an aerosol formulation to assess effects on
airway physiology, airway inflammation and symptom perception in
normal controls and those with asthma. The effects of fragrances
were evaluated in people without asthma, people with mild asthma
and people with moderate asthma in a four-way crossover placebo-
controlled study. Subjects were exposed twice to a fragranced
aerosol and twice to a placebo aerosol (15 and 30 min each).
Subjects completed a questionnaire for 29 symptoms during and up
to 3 hours after each exposure scenario. Spirometry was performed
prior to and 3 hours post-exposure; sputum induction was conducted
3 hours post-exposure. Nasal symptoms showed the greatest
frequency of response in all three subject groups, and moderate
asthmatics reported the greatest symptom severity and symptom
types. Insignificant differences were noted in physiology or cellular
inflammation. In conclusion, a trend for increased symptoms was
noted in moderate asthmatics, suggesting that asthma severity may
play a factor in fragrance sensitivity (36).
Fragranced consumer products, such as cleaning supplies, air
fresheners, and personal care products, can emit a range of air
pollutants and trigger adverse health effects. This study investigates
the prevalence and types of effects of fragranced products on
asthmatics in the American population. Using a nationally
representative sample (n=1,137), data were collected with an on-line
survey of adults in the U.S., of which 26.8% responded as being
medically diagnosed with asthma or an asthma-like condition.
Results indicate that 64.3% of asthmatics report one or more types of
adverse health effects from fragranced products, including
respiratory problems (43.3%), migraine headaches (28.2%), and
asthma attacks (27.9%). Overall, asthmatics were more likely to
experience adverse health effects from fragranced products than
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non-asthmatics (prevalence odds ratio [POR] 5.76; 95% confidence

interval [CI] 4.34-7.64). In particular, 41.0% of asthmatics report
health problems from air fresheners or deodorizers, 28.9% from
scented laundry products coming from a dryer vent, 42.3% from
being in a room cleaned with scented products, and 46.2% from
being near someone wearing a fragranced product. Of these effects,
62.8% would be considered disabling under the definition of the
Americans with Disabilities Act. Yet 99.3% of asthmatics are exposed
to fragranced products at least once a week. Also, 36.7% cannot use
a public restroom if it has an air freshener or deodorizer, and 39.7%
would enter a business but then leave as quickly as possible due to
air fresheners or some fragranced product. Of asthmatics, 35.4%
have lost workdays or a job, in the past year, due to fragranced
product exposure in the workplace. More than twice as many
asthmatics would prefer that workplaces, health care facilities and
health care professionals, hotels, and airplanes were fragrance-free
rather than fragranced. Results from this study point to relatively
simple and cost-effective ways to reduce exposure to air pollutants
and health risks for asthmatics by reducing their exposure to
fragranced products (37).
Perfume- and cologne-scented advertisement strips are widely
used. There are, however, very few data on the adverse effects of
perfume inhalation in asthmatic subjects. This study was undertaken
to determine whether perfume inhalation from magazine scent strips
could exacerbate asthma. Twenty-nine asthmatic adults and 13
normal subjects were included in the study. Histories were obtained
and physical examinations performed. Asthma severity was
determined by clinical criteria of the National Heart, Lung, and Blood
Institute (NHLBI). Skin prick tests with common inhalant allergens
and with the perfume under investigation were also performed. Four
bronchial inhalation challenges were performed on each subject
using commercial perfume scented strips, filter paper impregnated
with perfume identical to that of the commercial strips, 70%
isopropyl alcohol, and normal saline, respectively. Symptoms and
signs were recorded before and after challenges. Pulmonary function
studies were performed before and at 10, 20, and 30 minutes after
challenges. Inhalational challenges using perfume produced
significant declines in FEV1 in asthmatic patients when compared
with control subjects. Insignificant change in FEV1 was noted after
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saline (placebo) challenge in asthmatic patients. The percent decline

in FEV1 was significantly greater after challenge in severely asthmatic
patients as compared with those with mild asthma. Chest tightness
and wheezing occurred in 20.7% of asthmatic patients after perfume
challenges. Asthmatic exacerbations after perfume challenge
occurred in 36%, 17%, and 8% of patients with severe, moderate, and
mild asthma, respectively. Patients with atopic asthma had greater
decreases in FEV1 after perfume challenge when compared with
patients with nonallergic asthma. In conclusion, perfume-scented
strips in magazines can cause exacerbations of symptoms and airway
obstruction in asthmatic patients. Severe and atopic asthma
increases risk of adverse respiratory reactions to perfumes (38).

NEUROTOXICITY. Fragrance compounds are chemicals belonging

to one of several families, which are used frequently and globally in
cosmetics, household products, foods and beverages. A complete list
of such compounds is rarely found on the ingredients-list of such
products, as "fragrance mixtures" are defined as "trade secrets" and
thus protected by law. While some information regarding the
general toxicity of some of these compounds is available, their
neurotoxicity is known to a lesser extent. The prevalence and
neurotoxicity of fragrance compounds belong to the three most
common groups: phthalates, synthetic musks and chemical
sensitizers (39).

AUTISM. Autism spectrum disorder(s) (ASD) are developmental

conditions characterized by deficits in social interaction, verbal and
nonverbal communication, and obsessive/stereotyped patterns of
behavior. Although there is no reliable neurophysiological marker
associated with ASD, dysfunction of the parieto-frontal mirror neuron
system and underdeveloped olfactory bulb (OB) has been associated
with the disorder. It has been reported that the number of children
who have ASD has increased considerably since the early 1990s. In
developed countries, 1-1.5% of children have ASD, and in the U.S.
one in 88 children suffers from ASD. Currently, there is no known
cause for ASD. During the last three decades, the most commonly
accepted paradigm about autism is that it is a genetically inherited
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disease. The recent trio analyses, in which both biological parents

and the autistic child's exomes are sequenced, do not support this
paradigm. On the other hand, the environmental factors that may
induce genetic mutations in vitro have not been clearly identified,
and there is little irrefutable evidence that pesticides, water born
chemicals, or food preservatives play critical roles in inducing the
genetic mutations associated with known intellectual deficiencies
that have been linked to ASD. Here, scientific evidence is provided
that ASD is the result of exposure to perfumes and cosmetics. The
highly mutagenic, neurotoxic, and neuromodulatory chemicals found
in perfumes are often overlooked and ignored as a result of a giant
loophole in the Federal Fair Packaging and Labeling Act of 1973,
which explicitly exempts fragrance producers from having to disclose
perfume ingredients on product labels. It has been hypothesized that
perfumes and cosmetics may be important factors in the
pathogenesis of ASD. Synthetic perfumes have gained global utility
not only as perfumes but also as essential chemicals in detergents,
cosmetics, soap, and a wide variety of commonly used items, even in
food flavoring to enhance product taste. A majority of perfumes are
highly mutagenic at femtomolar concentrations, and cause significant
neuromodulations in human neuroblastoma cells at extremely low
levels of concentration, levels that are expected to reach a
developing fetal brain if the pregnant mothers are exposed to these
chemicals (40).

CHILDREN EXPOSURE TO FRAGRANCES. Hjorth in his classic

monogram "Eczematous Allergy to Balsams" emphasized that
sensitization to balsam of Peru is most important since secondary
allergens such as "fragrances" are ubiquitous. The application of a
topical medication containing balsam of Peru to the skin of an infant,
particularly in the occluded diaper area, seems a great way to
sensitize the infant not only to balsam of Peru but also to the fragrant
environment (41).
When utilized in the perfuming of children's toys, fragrances
capable of inducing contact allergy in human skin may also become
bioavailable to children via the inhalation route. The aim of this
study was to determine the area-specific emission rates of 24
fragrances from a plasticized polyvinyl chloride (PVC) reference
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material that was meant to mimic a real plastic toy. This material
was introduced into an emission chamber for 28 days at handling
conditions or at worst-case conditions. As a result, fragrances can be
separated into three categories according to their emission rates
ranging from 0.0041 to 16.2 mg/m² × h, i.e., highly volatile,
semivolatile, and low-volatile compounds. Compounds of the first
and second categories were monitored with decreasing emission
rates. Substances of the third category were detected with
increasing emission rates over time. Higher temperatures led to
higher emission rates. The emission concentration of fragrances
from four real scented toys varied between 1.10 and 107 μg/m³ at
day 1 in the test chamber. Therefore, short-term inhalation exposure
to fragrances originating from toys was in the range of 0.53-2700
ng/kg BW/d for the children of age 1 and older. Long-term exposure
to these fragrances was calculated in the range of 2.2-220 ng/kg
BW/d. Besides household products and cosmetics, fragrances can be
found in toys for children. Some fragrances are known contact
allergens in the skin, but there is a lack of information on their effects
in the human respiratory tract. Here, fragrances present in a
plasticized PVC reference material were analyzed according to their
emission profiles and volatility. Volatile fragrances emitted from real
toys and thus may get inhaled under consumer conditions to
different extents (42).
In the revised European toy safety directive 2009/48/EC the
application of fragrance allergens in children's toys is restricted. The
focus of the present work lies on the instrumental analytics of 13
banned fragrance allergens, as well as on 11 fragrance allergens that
require declaration when concentrations surpass 100 microg per
gram material. Applying a mixture of ethyl acetate and toluene
solid/liquid extraction was performed prior to quantitative analysis of
mass contents of fragrances in scented toys. In addition, an easy-to-
perform method for the determination of emitted fragrances at 23
degrees C (handling conditions) or at 40 degrees C (worst case
scenario) has been worked out to allow for the evaluation of
potential risks originating from inhalation of these compounds during
handling of or playing with toys. For this purpose a headspace solid-
phase microextraction (HS-SPME) technique was developed and
coupled to subsequent gas chromatography-mass spectrometry (GC-
MS) analysis. Fragrance allergens were adsorbed (extracted) from
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the gas phase onto an 85 microm polyacrylate fiber while incubating

pieces of the scented toys in sealed headspace vials at 23 degrees C
and 40 degrees C. Quantification of compounds was performed via
external calibration. The newly developed headspace method was
subsequently applied to five perfumed toys. The emission of
fragrance allergens from scented toys depended on the temperature
and on the content of fragrance allergens present in those samples.
In particular, at conditions mimicking worst case (40 degrees C),
fragrance allergens in toys may pose a risk to children since
considerable amounts of compound might be absorbed by lung tissue
via breathing of contaminated air (43).
A method of gas chromatography-ion trap mass spectrometry
(GC-IT-MS) was developed for the determination of 21 fragrance
allergens in sticker toys, plush toys and plastic toys. The
experimental conditions, such as sample pretreatment conditions,
and the analytical conditions of GC-IT-MS, were optimized. The
sticker toy samples and plush toy samples were extracted with
acetone by ultrasonic wave, and the extracts were separated on an
Agilent HP-1 MS column (50 m x 0.2 mm x 0.5 microm), then
determined by IT-MS and quantified by external standard method.
The plastic toy samples were extracted by the dissolution-
precipitation approach, cleaned up with an Envi-carb solid phase
extraction column and concentrated by rotary evaporation and
nitrogen blowing, then determined by GC-IT-MS and quantified by
external standard method. The calibration curves showed good
linearity in the range of 0.002-50 mg/L with the correlation
coefficients greater than 0.996 8. The limits of quantification (LOQ,
S/N > 10) were 0.02-40 mg/kg. The average recoveries of the target
compounds spiked in the sample at three concentration levels were
in the range of 82.2%-110.8% with the relative standard deviations
(RSDs) of 0.6%-10.5%. The results show that this method is accurate
and sensitive for the qualitative and quantitative determination of
the 21 fragrance allergens in the 3 types of toys (44).

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CONCLUSION
Perfumes have been part of human life since Ancient Times. The
use of perfumes is documented in several civilizations in ancient
world.
In the Bible, there are precise descriptions of various perfumed
products and how they were used.
In the Ancient World, the adverse health effects of many
perfumes were unknown.
In modern days, the desire for a pleasant smell occupies people
throughout the world. Although perfumes, as mentioned in this
Research can have positive effects, there are possible adverse effects
of their usage including contact allergic dermatitis, systemic contact
dermatitis, contact urticaria, atopic dermatitis, eczema, nasal
congestion, ocular irritation, asthma, neurotoxicity, and autism.
Patients with these conditions are usually advised to avoid
fragranced products. Individuals who use perfumes, regardless of
type, should be aware of negative health effects.

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