One fragrance chemical used in perfumes, colognes, soaps, detergents and cosmetics has been found to damage brain tissue in the laboratory animals tested. The compound, called acetyl ethyl tetramethyl tetralin (AETT), was commonly used in the above mentioned consumer products until scientists realized the chemical demonstrated serious neurotoxic properties. In fact, the chemical was in widespread use as a fragrance component in cosmetic, toiletry and soap products for a period of 22 years before the problem was detected. The first laboratory evidence of a problem came after researchers detected repeated percutaneous exposure to AETT in rats resulted in an extraordinary blue discoloration of the skin and internal organs, followed by behavioral changes and degeneration of the white matter in the brain. Upon realizing the potential harm from this compound, the fragrance industry voluntarily discontinued its use. This action was accepted by the U.S. Food and Drug Administration (FDA) early in 1978.

In an attempt to further quantify the exact nature of the neurotoxic properties of AETT, detailed testing of the compound was conducted by Dr. Peter S. Spencer and colleagues at the Program for Environmental Neurotoxicology and Teratology at the Albert Einstein College of Medicine in New York. According to Dr. Spencer’s research,

"These studies show AETT to be a cumulative neurotoxin capable of inducing in the rat hyperirritability, limb weakness, and widespread structural nervous system damage characterized by neurocellular ceroid pigmentary degeneration and widespread demyelination."

Three groups of rats were exposed to AETT on their skin or via food at different doses for a period over several months. Summarizing the results the researchers stated,

"Neurological and behavioral dysfunction developed in proportion to the dose and duration of intoxication. Animals dosed with 18-100 mg/kg/day of AETT became hyperirritable with the onset of tissue discoloration. They were easily startled and did not show a normal habituation to auditory and tactile stimuli. There was excessive spontaneous motor activity, and animals commonly attempted to bite the examiner upon handling. By 3-4 weeks, high -dosed rats (over 25 mg/kg/day) developed a peculiar, intermittent back-arching syndrome (see picture). By 5-6 weeks, there was an abnormal hind-limb extensor reflex elicited when the hind feet were raised by lifting the tail. Gait abnormalities developed with time and, by 9 weeks, ataxia, limb weakness, foot-drop and eversion of the hind feet were apparent. This clinical picture remained largely unchanged throughout the remaining period of intoxication. However, a single high-dosed rat at 26 weeks developed a picture of extreme irritability, inability to stand, and clonic-like movements of the limbs which were exacerbated by external stimuli. Lower-dosed animals also developed weakness (25 mg/kg/day), hyperexcitability (18 mg/kg/day), or only blue discoloration (9 mg/kg/day).

Regarding the physical effects upon the brain, the researchers observed degeneration of the "myelin sheath" that surrounds the axons that connect brain cells. As stated by the researchers,

"Demyelination had begun at 8 weeks in animals receiving 36 mg/kg/day percutaneously, and was apparent by 14 weeks in rats receiving 25 mg/kg/day. Demyelination commenced with splitting of myelin sheaths at the intraperiod line, followed by the accumulation of fluid, which caused the formation of edematous myelin bubbles.

In conclusion, the researchers stated,

"This study has demonstrated AETT to be a cumulative neurotoxin in the rat, capable of inducing a complex spectrum of behavioral and neuropathological changes as a function of dose and time following exposure by oral or percutaneous routes. Behavior abnormalities commence with hyperirritability and, depending on dosage, may progress temporally to ataxia and weakness. These behavioral and neurological signs are associated with the early appearance of neurocellular pigmentation and the subsequent development of widespread demyelination and scattered axonal degeneration in the central peripheral nervous systems."

Although AETT was subsequently removed from consumer products, it dramatizes the potential for neurotoxic compounds to be allowed in public use as it took 22 years before the problem was acknowledged and corrected. Because of the ubiquitous nature of fragrance compounds and their close source contact to the individual, and therefore the embryo and fetus, a cautious attitude concerning fragrance compounds during pregnancy should be maintained.

Common Fragrance Ingredient
Damages Connections Between Brain Cells

Toxicology and Applied Pharmacology, Volume 75:571-575 (1984)

Musk Ambrette is the name given to a commonly used fragrance ingredient, that according to researchers, causes serious brain damage in laboratory animals exposed to the chemical.

Musk Ambrette, whose chemical name is 2,6-dinitro-3-methoxy-4-tert-butyltoluene, is a common fixative ingredient that is currently added to fragrances in order to slow their evaporation, thereby making it more attractive to the consumer. It is found within most fragrances at a level of 1 to 3.5%. The chemical is also used to a lesser extent as an artificial flavor in compositions such as cherry, nut, spice vanilla, and mint.

The neurotoxic properties of Musk Ambrette are well established and as stated by the researchers,

"Musk ambrette, a nitro-musk compound widely used as a fixative in fragrance formulations and found to a lesser degree in flavor compositions, produces hindlimb weakness when administered in the diet or applied to skin of rats for periods up to 12 weeks. Underlying neuropathologic changes consist of primary demyelination and distal axonal degeneration in selected regions of the central and peripheral nervous system."

Primary demyelination means that the insulative myelin sheath surrounding the nerve cell connections are slowly being worn away. Degeneration of the axons means the actual connection from brain cell to brain cell is being destroyed by the chemical.