Introduction

The topic our group chose arose from the notion that the popular media has glamorized certain toxins. From movies to television shows to music, the overexposure of these toxins in products and services surrounding our daily lives has allowed them to become more acceptable and tolerable in our mainstream society.

The presentation will cover the crucial information of certain toxins used for cosmetic purposes such as BOTOX® Cosmetic and chemical peels as well as the toxins found in illegal drugs such as cocaine and thujone in absinthe.

Botulinum Toxin in BOTOX® Cosmetic

The BOTOX® Cosmetic website defines botulinum toxin injections as “a prescription medicine that is injected into muscles and used to improve the look of moderate-to-severe frown lines between the eyebrows (glabellar lines) in adults younger than 65 years of age for a short time (temporary)” (BOTOX® Cosmetic, 2010).

In 1949, Burgen’s group discovered that neuromuscular transmission gets blocked when in contact with the Clostridium botulinum toxin. In 1973, Alan B. Scott, MD, of the Smith-Kettlewell Eye Research Institute experimented with the botulinum toxin type A (BTX-A) on monkeys; by 1980, BTX-A was used for the first time in humans. In December 1989, BOTOX® was approved by the FDA and could officially be administered through injections. BOTOX® and BOTOX® Cosmetics then originated and is now manufactured by Allergan Inc. (a global pharmaceutical company that specializes in neuromodulator, eye care, and skin care) in Irvine, California for both therapeutic and cosmetic use (BOTOX® Cosmetic, 2010). According to the American Society of Plastic Surgeons, as of 2007, BOTOX® Cosmetic injections were the most common cosmetic operation and accounted for 4.6 million procedures in the United States.

BOTOX® Cosmetic contains botulinum toxin typeA (active ingredient) as well as human albumin and sodium chloride (inactive ingredients) (BOTOX® Cosmetic, 2010). The active botulinum toxin included in the ingredients has been purified for medical purposes so it will be less likely to cause botulism. In the unpurified form, the toxin interferes with nerve impulses and weakens or paralyzes the nerves that can cause abnormal muscle contractions for a period of time (Simpson, 1981).

Clostridium botulinum is a spore-forming, obligate anaerobe whose natural habitat is the soil. Unique strains of Clostridium baratii and Clostridium butyricum also have the capacity to produce the botulinum toxin (Simpson, 1981). The botulinum toxin is on of the most poisonous substance known. It is colorless, odorless, and tasteless. The lethal dose of botulinum toxin for humans has been estimated from previous primate studies. It is very toxic with an LD₅₀ of 0.005-0.05 µg/kg. A single gram of crystalline toxin would kill more than 1 million people if it were evenly dispersed and inhaled (even though technical factors make this scenario difficult). Due to these factors, it is even believed that botulinum toxin can pose as a major bioweapon threat. It not only has extreme potency and lethality, but it is easy to produce, transport, and misuse (Arnon, 2001).

The potency of the botulinum toxin is enzymatic. The structure consists of a di-chain polypeptide containing a 100-kd “heavy” chain joined to a 50-kd “light” chain by a disulfide bond. Since the light chain is a protease, it cleaves specific sites of the SNARE proteins (i.e. syntaxin, synaptobrevin, or SNAP-25) at the nerve terminus (the SNARE protein cleaved depends on the antigenic type of botulinum toxin present; botulinum types range from A through G). In turn, this prevents the complete assembly of the synaptic fusion complex (does not allow the synaptic membrane vesicles from attaching to the neuronal cell membrane) to release acetylcholine (a chemical compound that acts as a neurotransmitters in the nervous system) (Simpson, 1981). As previously stated, the inhibition of acetylcholine in the nervous system interferes with the normal functioning of nerve impulses, which can cause a weakened and sagging paralysis of the muscles due to the occurrence of botulism (Arnon, 2001).

Even though BOTOX® Cosmetics uses a purified version of the botulinum toxin and has low levels of toxicity, it is still likely to spread to areas of the body away from the injection site and cause major side effects including headaches, double vision, blurred vision, drooping eyelids, flu-like symptoms, allergic reactions, dysphonia, and dysarthria. Some life threatening side effects include problems breathing and swallowing. It also still carries the threat of being inhaled by the patient, which in turn can prove to be dangerous (BOTOX® Cosmetic). However, equine antitoxins (Trivalent Botulinum Antitoxin and Heptavalent Botulinum Antitoxin) have been derived to prevent such dangerous situations from occurring (Arnon, 2001).

Phenol in Chemical Peels

Chemical peels are a cosmetic treatment used to improve the texture of facial skin by causing dead skin cells to slough and peel off leaving behind smooth skin and a more rejuvenated and revitalized appearance. They can be used to correct sun exposure and aging spots, smooth out wrinkles, and remove precancerous growths (Corey, 2005).

Chemoexfoliation has been around since the late 1800s; by the 1930s and 1940s, physicians began to perform clinical trials and tests to determine if it should be allowed in the medical community. As time has passed, chemical peels have become more intricate and more varied. According to the American Society of Plastic Surgeons, as of 2007, chemical peels were one of the most common cosmetic operations and accounted for 1.03 million procedures in the United States (Corey, 2005).

There are three categories of chemical peels: light, intermediate, and deep. However, there are numerous types of chemical peels that fall into these three categories including: alpha hydroxy acid (AHA), beta hydroxy acid (BHA), trichloroacetic acid (TCA), glycolic acid, kojic acid, retinoic acid, Baker-Gordon, Jessner’s, and phenol. For this project, the group focused mainly on phenol chemical peels. The chemical solution used for phenol chemical peels is the strongest because it is used for deep skin chemical peels (Corey, 2005). It consists of two active ingredients that when mixed together causes an intense reaction that induces the exfoliating effects of the peel, croton oil and phenol (croton oil is considered to be a vehicle for phenol and the depth of the peel is more dependent on the concentration of croton oil and not phenol). However, of the two ingredients, phenol has been documented as being very toxic to humans due to its ability to denature keratin and allow it to penetrate deeper into the skin (Tisler, 1997).

The organic compound phenol (also known as carbolic acid) is composed of a six-membered (phenyl group; C₆H₅-) aromatic ring, bonded directly to a hydroxyl group (-OH). It is soluble in water and slightly acidic, which requires careful handling. Phenol was discovered in 1834 when it was extracted from coal tar. It can be made from the partial oxidation of benzene by either the cumene (isopropyl benzene) process or the Raschig-Hooker process or as a product of coal oxidation. Phenol is produced on a large scale, as it is a precursor to many useful materials and compound (i.e. drugs, plastics, etc.) (Tisler, 1997).

The toxicity of phenol is significant. Phenol can easily be absorbed through the skin (especially if it penetrates deep enough), quickly metabolized by the liver and its enzymes, and then excreted by the kidneys through the urine. Overdoses are very likely to damage the liver and kidneys and may eventually lead to problems of the central nervous system and heart (i.e. myocardial irritability/arrhythmias). The toxicity of phenol may also occur due to the formation of phenoxyl radicals in the body and its disturbances of certain body systems (especially respiratory, circulatory, etc.) (Conning, 1970).

Chemoexfoliation is safe, for the most part. However, like all cosmetic procedures, a risk is always present (as in deep chemical peels). The phenol and the produced vapors are corrosive to the skin, eyes, and respiratory tract. There are different ways the organic compound can enter the body though (e.g. through skin, through respiration, or eating and drinking products tainted with phenol) and each mode of transportation behaves differently. Repeated, prolonged skin contact with phenol can cause dermatitis or second/third-degree burns (if not decontaminated with polyethylene glycol, isopropyl alcohol, or water). However, if phenol is inhaled, the vapor is likely to cause pulmonary edema (Conning, 1970). There are methods to limit the possible side effects such as giving IV hydration to patient before and during procedure, extending the time of the full face peel to more than hour, and monitoring patients with telemetry after procedure is completed (Corey, 2005).

Cocaine

First synthesized in a pure form by Albert Niemann, cocaine from the the leaves of the Erythroxylum coca plant in the mountains of Peru and Bolivia was used as a cure for almost all illnesses and maladies in the late 1800s. In 1883, Theodor Aschenbradt administered cocaine to members fo the Bavarian army because it enhanced their endurance during manuevers. Cocaine was used in surgical procedures as a surface anesthetic for numbing or as a general anesthic for rendering a person unconscious. Africans combined it with caffeine to make a brain tonic recommended for headaches, drepression, fatigue, alcoholism, morphine addiction, abdominal pain, and menstrual cramps. Its positive effects were documented, published, and eventually picked up all over the world.



In North American in the early 1900s, cocaine was used in tonics, toothache cures, patented medicines, and chocolate flavored tablets. To increase sales, advertisements called that cocaine “could make the coward brave, the silent eloquent, and the render the sufferer insensitive to pain.” The addition alcohol yielded a more potent compound called “cocaethylene,” a popular ingredient found in Vin Mariani wine back then that was positively endorsed by prime-ministers, royalty, and even the Pope. However, its common usage as anesthetic made the public aware of its addictive potential. This was discovered specifically William Halstead conducted experiments testing the effectiveness of cocaine as an anthesia. Called the “Father of American Surgery” and one of the four founders of John Hopkins Medical School, Halstead experimented on himself and became addicted. When his addiction threatened to end his career, Halstead switched to morphine, a habit that he kept until he died.




Because of its high rate of addiction, cocaine’s use is highly limited. It is used in eye surgey as an anestheitc. Because of its property of vasoconstricting blood vessels, cocaine is used to stop nose bleeds and used as an anesthetic for cuts for small children. LD50 is 95.1mg/kg




The most extensively studied effect of cocaine is its effect on the central nervous system. It blocks the reabsorption of dopamine by the dopamine transporter protein so that dopamine accumulates in the synaptic cleft. As a result, there is a strong, prolonged effect of dopamine signaling at the receptors on the receiving neuron. Prolonged use causes a change in the body’s homeostatic level causing withdrawal symptoms when cocaine use is stopped.

Thujone in Absinthe

(Alpha-thujone)

Alcoholic beverages have seen their fair share of bans around the globe. From the absolute ban of alcohol is countries such as Libya, Saudi Arabia, Bangladesh, Sudan and a few other countries, to the prohibition of alcohol era of the United States in the 1920’s. In countries where alcohol has been permitted to be purchased, manufactured and consumed there is one type of liquor that has been banned from a handful of countries and only in recent times has become legal in a dilute form, the liquor absinthe. The reason behind the ban on this liquor is from the presence of thujone. Thujone is a chemical toxin isolated from Artemisia absinthium, commonly known as wormwood. Historically thujone content in absinthe was around 350 ppm. Current available content of legal absinthe is 9 ppm.






Wormwood isolates have been used in medical remedies for years. Alpha-thujone has also been used as an antinociceptive (reducing sensitivity to painful stimuli), insecticidal, and anthelmintic (an agent that causes expulsion of parasitic intestinal worms) activity (Hold, 2000). It is has also been used to treat loss of appetite, dyspeptic disorders and liver and gallbladder conditions (Blumenthal, 1998). Alpha-thujone is considered the active stereoisomer between the two compounds (Hold, 2000).






Alpha-thujone acts as a receptor antagonist (competes and blocks agonist binding sites). Alpha-thujone activates the GABA receptor, which upon activation Cl- ions pass through the pores resulting in hyperpolarization of the neuron. This action in turn prevents the opportunity for successful action potential. The neurotoxic effects that alpha-thujone causes in mice has been recorded to induce convulsion action that occurs when GABA-gated chloride channel are activated. In mice the LD50 is 45mg/kg.(Hold, 2000).

Conclusion

Even though toxins used for cosmetic purposes and found in illegal drugs are highly purified and/or minimal and not likely to cause dangerous, adverse effects, it is important to remember that a toxin will have a risk regardless of purity. Since these toxins are seen in products and services with more regularity, it may falsely give the illusion to people that a lot of toxins may also not be as toxic as first thought. The society that we live in has made us believe that beauty and entertainment comes with a high price. However, I think they forgot to include that this high price is not necessarily monetary.

References

Botulinum Toxin in BOTOX® Cosmetic

Arnon, S. S., et. al. (2001). Botulinum toxin as a biological weapon. The Journal of the American Medical Association. 285, 1059-1070.

BOTOX Cosmetic. (2010). About BOTOX Cosmetic: What about safety. Retrieved April 10, 2010, from BOTOX Cosmetic website: http://www.botoxcosmetic.com/What_About_Safety.aspx

Simpson, L. L. (1981). Origin, structure, and pharmacological activity of botulinum toxin. Pharmacological Review. 33, 155-188.



Phenol in Chemical Peels

Conning, D. M. & Hayes, M. J. (1970). The dermal toxicity of phenol: an investigation of the most effective first-aid measures. British Journal of Industrial Medicine. 27, 155-159.

Corey, C. L. (2005). Facial chemical peels. Retrieved April 15, 2010, from Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery website: http://www.bcm.edu/oto/grand/11_10_05.htm

Tisler, T. & Zagorc-Koncan, J. (1997). Comparative assessment of toxicity of phenol, formaldehyde, and industrial wastewater. Water, Air, & Soil Pollution. 97, 315-322.


Cocaine

Barnett, G. (1981). Cocaine pharmacokinetics in humans. Journal Ethnopharmacol. Vol. 3 No. 2. 353–366

Carey, R.J. (2008). Cocaine effects on behavioral responding to a novel object placed in a familiar environment. Pharmacology Biochemistry Behavior. Vol. 88 No. 3. 265–271

Gay, G.R., et. Al. (1975). Cocaine: history, epidemiology, human pharmacology, and treatment. a perspective on a new debut for an old girl. Clinical. Toxicology. Vol. 8 No. 2. 149–178



Thujone in Absinthe

Hold, K. M. et al. (2000). Alpha-Thujone (the active component of absinthe): gamma-Aminobutyric acid type A receptor modulation and metabolic detoxification. Proceedings of the National Academy of Sciences of the United States of America. Vol. 97 No. 8, 3826-2831

Meschler, J.P. (1999). Thujone Exhibits Low Affinity for Cannobinoid Receptors But Fails to Evoke Cannabinmimetic Responses. Pharmacology Biochemistry and Behavior. Vol. 62, No. 3, 473-480.

Smith, P.E. (2006). Neurology and Art: Absinthe Attacks. Practical Neurology. Vol. 6, 276-381.