Safety of Fragrances: A Case for Concern

Introduction

Fragrances are found every where in our environment. Consumer products of all types are fragranced. Workplace exposures to fragrances are also common. Fragrances are found in cleaners, pesticides, and even machine cutting fluids. (1) Fragrance/flavors are added to cigarettes to enhance flavor, especially in the lower tar and nicotine brands. (2) Environmental tobacco smoke is another source of exposure to fragrance chemicals.

Exposure to fragrance materials occurs through numerous routes. Skin contact and absorption occurs when fragranced products are applied or used. Ingestion is a common route of exposure. Olfaction plays an important part in taste; fragrance chemicals and flavor chemicals are usually one and the same. The use determines whether they are referred to as a fragrance material or a flavoring material. Breathing in fragrances, is a route of exposure for both the upper and lower airways, as well as a neurological route of exposure. (3)

Those who wish to limit their exposures to fragrances are finding it difficult at best and impossible in most circumstances. There are multiple reasons for wishing to avoid contact with fragrances. For some they are simply intrusive, for others, the implications are much more serious. Exposures to fragrances are known to trigger asthma, sinus problems, dermatitis, and migraine headaches. (4,5,6) Those that have health problems triggered by exposure to fragrances often find it difficult to function in a “fragranced” world. Exposure to “second hand” fragrance is very difficult to avoid.

Conditions Affected by Fragrance

Airborne contact dermatitis is known to occur from exposure to musk ambrette and other fragrance chemicals. (7) Simply touching a surface that someone else with fragrance on their hands has touched can cause allergic reactions. In most studies of eczema patients, fragrances are ranked either first or second as the most common cause of problems depending on the population studied. Fragrance is the number one cause of adverse skin reactions to cosmetics and laundry products. In Denmark, a study showed 6.3% of 3,440 eczema patients tested had sensitivity to fragrance. A German study showed 15.3% of 9,835 eczema patients had sensitivity to fragrance. The German population uses twice the amounts of cosmetics the Denmark uses. There is a direct relationship between the amount of exposure and the percent of the population with adverse skin reactions to fragrances. (1) In Denmark it is estimated that 1-2% of the population has fragrance allergy. (8) Conceivably the numbers in the USA are higher.

Fragrance chemicals are generally volatile organic compounds. These substances are known to contribute to poor indoor air quality. Poor air quality can contribute to health problems. Recent studies have shown that in the presence of ozone these chemicals break down into very irritating substances. These substances are short-lived and often difficult to detect. Many fragrance chemicals are air, light, and heat sensitive. Often the breakdown products are more toxic than the original substance. The mixture in air constantly changes as the chemicals interact and new ones are added as fragrances volatilize. Equipment producing heat, light and ozone affect the breakdown of these chemicals. What is in the air may vary on a day to day basis. Irritants in the air are known to contribute to upper and lower respiratory problems.

Those suffering from allergies often find exposure to fragrance causes stuffy noses, runny eyes, and a general exacerbation of problems predisposing to acute and chronic sinus infections. Irritant reactions often cause the same symptoms as allergic ones. It is difficult to tell if the basis of a problem is allergy or irritant. The problem may be a combination of both. Irritants will cause problems for anyone, though they affect some at lower levels than others. Irritants found in ambient air can cause immediate problems for some, while others are seemingly unaffected. Rhinitis, sinusitis, and asthma can result from irritant reactions as well as allergic ones. Non-allergic reactions generally do not respond well to medication and avoidance is the best way to avoid symptoms.

For those with asthma and Chronic Obstructive Pulmonary Disease (COPD), the problems are often more serious. Irritants in the air often trigger bronchoconstriction of the airways of those suffering from asthma, COPD, and other respiratory problems. Continued exposures can contribute to deterioration of health, poor control of the disease, and increasing need for medication. For some, medication provides only limited relief or the associated side effects are of major concern. There is a subset of those with asthma that seems to be specifically triggered by exposures to fragrances, often at very low levels. (4) This points toward the possibility of respiratory sensitization to specific substances, rather than a response to an irritant.

The possibility of respiratory sensitization is of special concern. If common environmental substances such as fragrances can cause respiratory sensitization similar to that found in work exposures to isocyanates, the implications are serious. While several studies have shown asthma can be triggered by exposure to fragrance, there was no attempt to determine if the asthmatic response was due to the irritant quality of the fragrance or if there was sensitization to specific ingredients.

Skin studies have determined that the fragrance chemical cinnamaldehyde acts as a hapten in the skin to bind with proteins to cause allergy. (9) This same mechanism is thought to occur in respiratory sensitization to isocyanates. (10) Isocyanates and other chemicals can cause sensitization in the skin as well as in the lungs. In some studies dermal exposure to isocyanates triggered respiratory symptoms. (11)

Perfumes and fragrances are frequent triggers for migraine headaches. Some fragrance chemicals are known to cause circulatory and EEG changes in the brain when inhaled. (12) Vascular changes may be one mechanism by which migraines may be triggered. Olfactory pathways provide a direct route of exposure to the brain. In studies of mice exposed to fragranced products (FPs) there were obvious neurological effects. (13)

“The emissions of five FPs produced various combinations of acute respiratory difficulty and neurotoxicity in mice. The findings provided objective evidence that some FPs produce toxic effects in at least one mammalian species. Collectively, the experimental data and chemistry predict that some humans exposed to these FPs might experience some combination of eye, nose, and/or throat irritation; respiratory difficulty; possibly bronchoconstriction or asthma-like reaction; and central nervous systems reactions (e.g., dizziness, incoordination, confusion, fatigue).” (Acute toxic effects of fragrance products. Arch Environ Health. 1998 Mar-Apr;53(2):138-46. Anderson RC, et al.)

Industry Self-Regulation

While dermatology aspects of fragrances are recognized, other aspects have far less documentation. The fragrance industry is basically a self-regulated one. (14)

Fragrance materials are not required to be disclosed on labels because they have trade secret status. The term “fragrance” is used to designate the fragrance formulation used in the product. Any substance can be used in a fragrance other than a few that are specifically listed in FDA regulations. (15) No pre-market approval process is required, nor any safety testing. (16) FDA regulations do require any product that has not been adequately tested for safety bear a prominent warning label saying

“WARNING: The safety of this product has not been determined.”

At present fragranced products do not carry such a label despite the fact that many fragrance ingredients have this statement on MSDS and Chemical Data sheets:

“Potential Health Effects The toxicological properties of this material have not been investigated. Use appropriate procedures to prevent opportunities for direct contact with the skin or eyes and to prevent inhalation” (17)

In 1966 when questions of the safety of fragrance materials were raised, the Research Institute for Fragrance Materials was formed by the industry. The purpose of the RIFM is to oversee safety testing on substances used in fragrances. Depending on the source, the numbers of materials in use in the fragrance industry are between three and five thousand. The RIFM has conducted safety testing on less than 1500 of these materials. (14) The testing is generally limited to oral and dermal acute toxicity, irritant and allergy potential, and other skin effects. Testing for neurological and respiratory effects are not included in testing though these areas should be of significant concern.

In 1973 the IFRA (International Fragrance Association) was established. The RIFM submits the results of testing to the International Fragrance Association. The IFRA then makes recommendations as to the safe use of the tested fragrance materials. The IFRA issues “Industry Guidelines to Restrict Ingredient Usage”. There is no enforcement agency and compliance is voluntary.

Consumer complaints about fragrances and fragranced products that are considered cosmetics are under the jurisdiction of the FDA, while other consumer products come under the jurisdiction of the Consumer Product Safety Commission. However neither agency’s complaint protocol is set up to register complaints of problems from other’s use.

Concerns on Adequacy of Testing and Self-Regulation

There are legitimate concerns about the scope and effectiveness of safety testing by the fragrance industry. In the late 1970s it was found that Acetylethyltetramethyltetralin (AETT) caused the internal organs of laboratory animals to turn blue. This substance was also severely neurotoxic. (18) Testing by the industry had not pinpointed these side effects. It was discovered by accident after the material had been used in products for over 20 years.

Musk Ambrette (MA) was also used in fragrances since the 1920s. Testing by the RIFM indicated it was safe for use. It was later determined that MA caused photosensitivity reactions and had neurotoxic properties. The IFRA recommended in 1985 that Musk Ambrette not be used in products with skin contact. In 1991, MA was still being found in products tested by the FDA. (14)

Dr. Peter Spencer testified before Congress in 1986. This excerpt from Dr. Spencer’s testimony sums up concerns.

“Musk AETT(23) and Musk ambrette, two tested raw materials of the hundreds of untested chemicals used in fragrances and flavors have demonstrated potent neurotoxic effects and the capacity to induce the breakdown of nerve cells and myelin sheath in the brain, spinal cord, and peripheral nerves.(24) Countless other substances applied daily to the skin of consumers in the form of soaps, perfumes, aftershaves, and detergents have yet to be tested for their chronic neurotoxic effects.”

“I would also add, because of my experience with regard to fragrance raw materials, that I would strongly suspect the American public would like to know what is applied to their skin voluntarily, and I suspect that they would be very troubled to learn that for 50 and 30 years respectively agents have been applied to skin voluntarily, often under the guise that they are in fact improving skin quality, but are able to penetrate the skin, and a recent experiments with animals caused devastating changes in the pervious system. I would like to add fragrances raw materials, some of which are food additives as well, …
Excerpt from Dr. Spencer’s testimony to House of Representatives 99th Congress, 2nd Session. Report 99-827 NEUROTOXINS: AT HOME AND THE WORKPLACE

More recent concerns are being focused on Musk Xylol. MX was used to replace Musk Ambrette. Safety testing by the industry indicated it was safe for use. Later studies outside the industry found MX to be carcinogenic when feed to mice. MX has been used since the turn of the century. It accumulates in human tissue and has been found in human adipose tissue and breast milk. (19)

There are further concerns because MX is being found in aquatic wildlife. Several studies have determined there is water contamination and MX accumulates in the tissues of fish, mussels, and other aquatic wildlife. Sewage treatment does not remove MX and discharged wastewater contaminates rivers and streams. The implications are not clear, but are of great concern since MX is now in the food chain and has been determined to be a carcinogen when ingested by lab animals. Japan has removed Musk Xylol from use because of concerns. Despite mounting evidence that MX may not be safe and there is widespread exposure, the IFRA has not made any recommendations on eliminating its use. (14)

Recent studies have shown that combinations of sensitizers are synergistic and increase the sensitizing potential of a fragrance. (20) This same fact was shown by early testing methods used by the RIFM. Four materials are used together in patch testing. It was found when related materials were used the incidence of allergy was greatly increased. When unrelated materials were used there were fewer incidences of allergic reactions. It was then determined that related materials were not to be used together in patch testing, despite such combinations being common in fragrance formulas. (21)

A large percentage of skin allergies can be pinpointed by the use of the screening agent called “fragrance mix”. Fragrance Mix contains 8 known skin sensitizers and is diagnostic for 70-80% of those with skin allergies to fragrances. (22) The eight materials are:

  • *[Alpha]-amylcinnamic aldehyde (CAS# 122-40-7)
  • * Cinnamic alcohol (CAS# 104-54-10
  • * Cinnamic aldehyde (CAS# 104-55-2)
  • * Eugenol (CAS# 97-52-0)
  • * Geraniol (CAS# 106-24-1)
  • * Hydroxycitronellal (CAS# 107-75-5)
  • * Isoeugnol (CAS# 97-54-1)
  • * Oak moss (CAS# 9000-54-4)

Most fragrances contain more than one of these sensitizers. In a chemical analysis of the ten most popular women’s perfumes used in the USA, three to six of the sensitizers found in Fragrance Mix were present with the average being four in each product. (23) Despite these materials being known to sensitize the skin, they continue to be used.

Most of the testing the RIFM conducts revolves around skin effects. Although olfactory pathways provide direct connection to the nervous system, neurological testing is not done. Respiratory exposure is significant, especially since many fragranced products are spray products that produce highly respirable mists. At the least fragrances are respiratory irritants that exacerbate disorders of the upper and lower respiratory tract. Studies need to be done to determine if they are the cause of some of these problems.

 Perfumery Materials

The vast majority of fragrance materials in use now are either synthetics or isolates. (24) Isolates are obtained from materials with primarily a single chemical being extracted. Synthetics are made in the lab. Often materials are neither fully synthetic nor fully natural, but rather a combination of the two. (25)

Synthetics are usually derived from chemical reactions using crude oil or turpentine oil as the starting material. Synthetics are usually single molecules that are very different than the complex mixtures found in nature. Many synthetics are not found in nature at all. (26) There are trace impurities left over from the reaction process, and these impurities affect odor quality and safety of the synthetic material.

Natural materials typically come from plants, though in the past animal sources were also in common use. Some materials are complex mixtures that contain much the same components as found in nature, only in a very concentrated form. Essential oils, absolutes, concretes, and resinoids are examples of this. Some “natural” materials are isolates where individual compounds are extracted. Still other “natural” materials are made using fermentation processes. The odor quality of naturals, even when the same chemical, is usually different than synthetics. There are usually trace compounds that give it a different odor quality than the synthetic version.

Natural materials are not necessarily safer than synthetics. However, they have a much longer history of use so the adverse effects are better known. Natural materials are mixtures of sometimes hundreds of compounds. There are both synergistic and modifying effects of combinations of chemicals. The actions of these combinations are often very different than isolates or synthetics. (27)

Most fragrance materials are on the Generally Recognized as Safe List (GRAS). This designation is for these materials when they are used as food additives. Adequate testing has not been done to determine safety via other routes of exposure and in many cases safety testing was not done on safety of ingestion. Materials that were in use before 1958 as food additives were certified as GRAS based on their history of use. Very little actual safety testing was done. (28)

 Formulation

Classic perfumery is designed to have “notes”. The first note is composed of more volatile substances, which give an immediate effect. The middle note is the main body of the fragrance and the last note is the lingering quality of the fragrance. These notes blend together to form a pleasing scent that develops over a period of time on the user. A good perfume is designed to last 6-8 hours.

In the mid-eighties, a different method developed in formulating fragrances. These formulas use fewer compounds, but in larger amounts. The newer synthetic materials used are extremely powerful and long lasting. (25) These more powerful formulations are not only used in perfumes, but also products such as detergents and fabric softeners. Scents from laundry products now last for weeks.

New technologies are also being used. A material called cyclodextrin is used to create a slow release in things such as fabric softeners. Cyclodextrins have a doughnut shaped molecule. The fragrance is trapped inside the “hole”. Moisture causes the molecule to swell and the fragrance is released. This allows the scent from fabric softeners to last a long time.

There are generally more complaints of health problems from exposure to these newer more powerful fragrances. Whether the problems stem from ingredients that are more toxic, greater exposure, new technologies, or a combination of all is not known. Testing is needed to determine why these products are causing problems.

 Trends

In the past few decades there has been a tremendous increase in the use of fragrances and fragranced products. Functional products such as cleaners and laundry products are often more highly fragranced than traditional perfumery. Most personal care products such as shampoos, lotions, soaps, etc. also contain fragrance. There is increased usage of air fresheners, candles, and other products to scent the air. Retail establishments and some businesses pump fragrance through ventilation systems in hopes of increasing sales and increasing productivity.

The average person easily uses a dozen or more scented products in a day (29) and is exposed to hundreds. Fragrance are volatile and by design get into the air. Everywhere a person goes, a little of their fragrance is left behind. So there is exposure not only to the fragrance a person uses, but to fragrances others use also.

The fragrance market has been traditionally targeted toward adults. The trend now is toward younger and younger markets. The teenage market has been heavily targeted for the past decade. “Miss Piggy” and “Kermit” have their own line of fragrance. Avon is targeting children as young as three. (30,31)

Children are exposed to fragrances from birth. The exposure is greater for children since they are smaller and their skin is thinner and more is absorbed. A higher respiratory rate increases the amount taken into the lungs. Many fragrance materials have allergic, irritant, and neurological effects. Often microenvironments are created that increases exposure to infants. When an infant is wrapped in a blanket or held close there is increased exposure. An infant’s or child’s system is more susceptible to the effects of chemicals.

Because of the trend of increased usage of fragranced products, there is increased exposure. One can no longer consider just the exposures of a single product. This is especially true when substances accumulate in body tissues.

Conclusion

There are increased complaints of fragrances causing or triggering health problems. Fragrances are known to be triggers for health problems for those with problems such as asthma, allergies, sinus problems, and migraine headaches. Avoidance of triggers is extremely difficult because of the widespread use of fragranced products. This makes it difficult for individuals with fragrance sensitivity to function in the workplace and other public environments.

Gathering objective data as to the actual incidence of fragrance induced health problems is difficult because there is no program where all complaints about fragrances can be directed. Trade secret status further complicates matters. There is generally no readily available testing for fragrance sensitivity other than for skin reactions. The vast number of fragrance materials in use makes it difficult to pinpoint specific substances that cause problems. There is no program in place in which the industry will cooperate with doctors to determine which specific chemical/chemicals are involved in the adverse reaction. This is especially true when adverse effects do not pertain to the skin.

Safety of many of the materials used in fragrances has not been established. Industry testing does not address all routes of exposure, nor exposures to the complex mixtures of substances found in fragrances. Pre-market safety testing is not required. Cosmetics including fragrances are a low priority at the FDA and after market testing is the exception rather than the rule.

In order to determine the extent in which fragrances affect health much work is needed. The following need to be in place:

  1. Reliable methods of collecting data
    • a. A program for registering complaints from both users and non-users of products
    • b. Requirement for industry to collect and report complaints
  2. Establishment of a program for identifying materials and products that cause adverse reactions while protecting industry “trade secrets”.
  3. Safety testing on fragrance materials both individually and in common combinations.
  4. Safety testing via all routes of exposure with both acute and chronic effects examined.
  5. Safety be established for children for all products, but especially those products targeted toward new parents, infants, and children.
  6. Studies to establish the effects of fragrances on health.
  7. Establishment of a working committee to address issues of fragrance safety. The committee would be composed of those that are fragrance sensitive, doctors, FDA staff, and representative from the fragrance industry.

The above measures would help insure the safety of products for which there is an almost constant exposure.

REFERENCES:

  1. Fragrance contact allergy. Cosmetics and Toiletries July 1998 (v113 n7) Start Page: p47(4) ISSN: 0361-4387 Johansen, Jeanne Duus Menne, Torkil
  2. Environmental Health Perspectives, Volume 102, Number 9, September 1994
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  4. Placebo- controlled challenges with perfume in patients with asthma-like symptoms. Allergy 1996 Jun;51(6):434-9, Millqvist E, Lowhagen O
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  8. Perfume Causes Allergy. Danish Environment Internet Edition 2, September 1996: Niels moller Madsen.
  9. Interaction of cinnamaldehyde (a sensitizer in fragrance) with protein. Contact Dermatitis 1989 Mar:29(3):161-6. Weibel H, Hansen J
  10. A role for cellular immunity in the induction of airway hyperresponsiveness induced by small molecular weight compounds. Toxicol Lett 1994 Jun: 72(1-3): 151-4. Garssen J, Mijkamp FP, van der Vliet H, van Loveren H
  11. Dermal contact with toluene diisocyanate (TDI) produces respiratory tract hypersensitivity in guinea pigs. Toxicol Appl Pharmacol. 1981 Apr: 58(2):221-30. Karol MH, et al
  12. EEG and ERP studies of low-level odor exposures in normal subjects. Toxicol Ind Health 1994 Jul-Oct: 10(4-5):579-86. Lorig TS
  13. Acute toxic effects of fragrance products. Arch Environ Health. 1998 Mar-Apr;53(2):138-46. Anderson RC, et al.
  14. Nitro musks in fragrance products: an update of FDA findings (includes related article on self-regulation by the fragrance industry) Cosmetic and Toiletries. (v111 n6) Start Page: p73(4) ISSN: 0361-4387 Wisneski, Harris S. Havery, Donald C.
  15. U.S. Food and Drug Adminstration Center for Food Safety and Applied Nutrition Office of Cosmetics Fact Sheet February 23, 1995 “Prohibited Ingredients”
  16. U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition Office of Cosmetics Fact Sheet February 3, 1995. “FDA Authority Over Cosmetics”
  17. Acros Organics: Hexyl alcohol, 98 MSDS
  18. Neurotoxic fragrance produces ceroid and myelin disease. Science 1979 May 11;204(4393):633-5 Spencer PS, Sterman AB, Horoupian DS, Foulds MM
  19. Musk xylene: analysis, occurrence, kinetics, and toxicology.  Crit Rev Toxicol. 1998 Sep;28(5):431-76. Kafferlein HU, et al.
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  23. Contact Allergy to popular perfumes; assessed by patch test, use test and chemical analysis, Br J Dermatol 135 419-422 (1996) JD Johansen, SC Rastogi and T Menne,
  24. AROMA CHEMICALS AND THE FLAVOR AND FRAGRANCE INDUSTRY., Chemical Economics Handbook. p. 503.5000 A. Laszlo P. SomogyiBirgitta RhombergYasuhiko Sakuma
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  27. Immediate contact reactions to chemicals in the fragrance mix and a study of the quenching action of eugenol. Br J Dermatol. 1990 Nov;123(5):595-606. Safford RJ, et al.
  28. Code of Federal Regulations 21CFR170.30
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  30. CHILDREN’S FRAGRANCE GIFT SETS MAKE UNIQUE, AFFORDABLE PR Newswire Date: 03-Dec-1998 14:59
  31. The Children’s Market Approaching A New Millennium. Drug & Cosmetic Industry Aug-1998 Vol. 163 Iss. 2 Pg. 46. Courtnay Sander

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