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Cosmetics

Botox - Animal cruelty for a questionable beauty

Botox is the brand name of one of the products containing the nerve poison botulinum toxin. The toxin is used for medical and increasingly for cosmetic applications. A small injection causes facial wrinkles to disappear. But the price for the short term 'beauty' is paid by the suffering and death of thousands of mice. 

Each batch is tested before it reaches consumers. A sample is injected into the abdomen of mice. The mice suffer paralysis, impaired vision and respiratory distress. After three or four days of suffering, they die from suffocation. Since 2007 Doctors Against Animal Experiments have been running the campaign 'Stop Botox animal testing' to inform the public, to put pressure on the manufacturers still testing on animals as well as on authorities to speed up the validation and implementation of animal-free methods and to remove the mouse assay in the EU legislation.

Success

Animal-free testing methods are already available, but not all manufacturers use these. In 2011 the campaign led to a first success: market leader Allergan got a regulatory approval for a non-animal test in the US, Canada and the EU. The German company Merz received an approval for a cell-based assay in 2015. In August 2018, the French manufacturer Ipsen finally received approval in the EU and Switzerland for a cell-based test - 7 years after Allergan. However, all three companies replace only a large part of their animal experiments.

Despite these successes, an estimated 400,000 mice per year are subjected to a cruel death by asphyxiation in Europe only.

Our campaign will be continued until no mouse has to die for botulinum toxin products anymore.

What is Botox?

'Botox' is a brand name of a product which is manufactured using the bacteria poison botulinum toxin. Because of its frequent use in the mass media the name 'Botox' has been established in the public’s mind as a generic term for the injectable anti-wrinkle treatment with the bacteria toxin. 

Botulinum toxin is produced by the bacterium Clostridium botulinum which can occur in contaminated meat tins. It is the most powerful currently known poison. Inconceivable small amounts, a hundred thousandth milligram, can kill a person. 

It blocks the signal transmission from nerve to muscle. The muscle gets paralyzed. A poisoned person dies of suffocation after the respiratory muscles become paralyzed. If highly diluted these properties can be used for the treatment of several medical conditions, including cervical dystonia, torticolis, blepharospasm, hyperhidrosis, strabismus and migrane. 

Injecting Botox in facial muscles paralyzes them and causes the facial skin to smooth out. This effect lasts two to six months. That's how long it takes the body to build new nerve endings.

How is Botox tested on animals?

Because the toxin is potentially highly dangerous, it must be much diluted prior to application as a drug for humans. The manufacture process can cause variations in potency. Therefore, each batch is tested for its potency before marketing. 

The standard procedure is a classic LD 50 test. Groups of mice are injected with different doses of Botox in the abdomen. The LD50 test causes substantial pain and suffering for the mice. The animals undergo paralysis, impaired vision and respiratory distress. After three or four days of suffering they finally die from suffocation. 

For the testing of chemicals, modified LD50 test protocols have been accepted for several years. These tests require fewer animals and are apparently less painful. However, even these small improvements are not accepted for testing Botox. The classical LD50 test continues to be performed which requires death as the endpoint. 

Apart from the batch testing for each newly registered product or if changes in the production process are occurring so called stability tests are performed. These tests are conducted in the first five years after the formal registration and require particularly large numbers of animals

Approximately 100 mice are being used to test each batch of botulinum toxin products. (1) In 2008, 74 000 mice suffered and died in botox tests for the company Ipsen, while 34 000 died for Merz during the same year. According to global projections, in 2008, the three major companies Allergan, Merz and Ipsen used an estimated 600,000 mice. (2) According to more recent research, in Europe alone, about 400,000 mice were subjected to this cruel death (3) – globally this figure is likely to be much higher as the huge markets in Asia and North-America are not included. Due to the continually high demand for botox, the number of mice killed is likely to continue to rise.

What are the mice subjected to?

An undercover investigation conducted by Cruelty Free International at the Wickham Laboratories, Hampshire, UK between February and October 2009, showed mice dying in agony. The animals had been injected with the botulinum toxin product Dysport®.

 

Which 'alternatives' are available?

The manufacturers Allergan and Merz received regulatory approvals for their cell-based assays in the U.S., Canada, the EU and Switzerland in 2011 and 2015, respectively. The assays were developed in-house and use human nerve cells. So far, however, both companies have replaced only a large part of their animal tests, the batch testing. Allergan expects an 80% replacement of its Botox animal tests. 20% are still being used for the so called bulk testing and legal requirements in other countries. (4) Merz has reduced its animal testing from 90,000 in 2014 to around 11,400 in 2016. (5) The French manufacturer Ipsen claimed in August 2018 to have received a license in the EU and Switzerland for a cell-based test. The company did not reveal how many animals are spared in this way. (6)

How is Botox regulated?

The European Pharmacopoeia is a kind of menu for the production, labelling, testing and storing of pharmaceutical products in Europe. The regulations are set by an EU authority, the European Directorate for the Quality of Medicines & Health Care (EDQM) in Strasbourg, France. 

The European Pharmacopoeia requires that for every batch of botulinum toxin an LD50 test is carried out on mice (7). Botox products are approved as drugs, which is why the EU Cosmetic Directive which bans testing cosmetic products on animals does not apply here. In addition the Directive defines cosmetic products as being applied topically (to the skin and so forth), whereas botox products are injected. 

However,  manufacturers can develop and validate their own alternative assays if these yield the same results as the mouse test. The alternative test is then accepted only for their product.
Botox products are approved as drugs, which is why the EU Cosmetic Directive which bans testing cosmetic products on animals does not apply here. In addition the Directive defines cosmetic products as being applied topically (to the skin and so forth), whereas botox products are injected. 

Doctors who use botox-type products for aesthetic purposes are doing this mostly 'off label'; this means that the drug has not been approved for this purpose. Depending on which preparation is used patients have to sign an agreement that they are being treated at their own risk with a drug that has not been officially approved for treating wrinkles. Botox Cosmetics®, Vistabel® and Azzalure® are licensed for the temporary treatment of certain wrinkles such as frown lines. All other cosmetic applications are done 'off label'.

How was Botox discovered?

Botulinum toxin was found in tins of contaminated meat. In 1895 the Belgian microbiologist Emile Van Ermengen identified the bacterium Clostridium botulinum as the causative agent of the deadly 'sausage poison'. He called it 'botulinum toxin' after the Latin words 'botulus' = sausage and 'toxin' = poison. 

In 1946 botulinum toxin A was purified for the first time. Monkeys were used to test the paralyzing effects. In the 1980’s it was used to treat people suffering with cross eyes by injecting the toxin into the eye muscles. More medical indications were soon found. In 1989, Allergan received approval for its drug Oculinum for the treatment of strabism, blepharospasm and other muscle conditions. Later the product was renamed BOTOX. Nowadays more than 50 nerve and muscle diseases can be treated with botulinum toxin. (1) 

Since 1992 the toxin has been increasingly used for cosmetic purposes. In 2002, Allergan's BOTOX © COSMETICS received approval in the U.S. (1). Soon the bacteria poison became a lifestyle drug and a worldwide big seller.

Which companies are producing botulinum toxin?

There are 9 distinct types of botulinum toxin, referred to as types A, B, C etc.. Botulinum toxin A is primarily used for medical and cosmetic purposes. Botulinum toxin B is also available as a drug. 

Manufacturers of botulinum toxin A products:

Allergan Inc., P.O. Box 19534, Irvine, CA 92623, USA

BOTOX® is the original product. In 2002 BOTOX® COSMETICS gained approval for cosmetic applications in the U.S. It is manufactured in smaller dosages than BOTOX® which is destined for medical purposes. BOTOX® COSMETICS is marketed in European countries as Vistabel®. Production and animal tests for the European market were carried out in Ireland. Allergan received regulatory approval in the U.S., Canada and the EU for a cell-based assay for most of their animal tests. (4)

Ipsen Ltd., 190 Bath Road, SL1 3XE Slough, UK

Dysport® is approved for medical applications only. The animal experiments were carried out at the Wickham Laboratories, UK, and maybe in Ireland. Ipsen claims to have received approval for a cell-based test from authorities in the EU and Switzerland in August 2018. (6)

Merz-Pharma GmbH & Co. KGaA, Eckenheimer Landstraße 100, 60318 Frankfurt, Germany

Xeomin® is approved for two medical purposes only: the treatment of torticollis and blepharospasmus. Bocouture® is licensed for the treatment of frown lines. The animal tests are conducted at the contract testing lab LPT in Hamburg, Germany.  In 2015 Merz’s cell-based assay was approved in the EU and Switzerland. (5)

Croma Pharma GmbH, Industriestraße 6, 2100 Leobendorf, Austria

The Austrian company Croma has acquired a license in 2014 to distribute botulinum toxin A products of the Korean company Hugel in Europe and North America. Distributor in Germany is the company Stada AG. Currently the product is not on the market yet.

Galderma Ltd., Meridien House, 3rd Floor, 69 - 71 Clarendon Road, Watford, Hertfordshire, WD17 1DS, UK

Galderma was originally a joint venture of Nestlé and L'Oreal. In 2014, it was fully acquired by Nestlé. Azzalure® is the same as Ipsen's Dysport® for cosmetic purposes.

Nestlé Suisse S.A, PO Box 2222, 1800 Vevey, Switzerland: Dysport®, Azzalure®

Food giant Nestlé entered the Botox business in 2015. The Swiss company sells the botulinum toxin products Dysport® and Azzalure® from the manufacturer Ipsen through the newly established Nestlé Skin Care branch.

Eisai GmbH, Lyoner Str. 36, 60528 Frankfurt am Main: NeuroBloc®

The Japanese company Eisai distributes the botulinum toxin B preparation Myobloc® of the American company Solstice under the name NeuroBloc® exclusively in Europe. NeuroBloc® is approved for the treatment of torticollis. Botulinum toxin B takes effect earlier, but it only lasts for a short time. An off-label use in the cosmetics sector is therefore not effective. Some patients develop neutralizing antibodies due to excessive Botox use with the result that the injections are no longer effective. In these cases botulinum toxin B can be used. It can be assumed that the use of NeuroBloc® in the cosmetics sector will become increasingly important in the future (1). Eisai has a branch office in Frankfurt, Germany. The animal experiments are commissioned to the laboratory LPT in Hamburg.

There are many other suppliers of Botox products: Acorda Therapeutics, Aldeyra Therapeutics, Azidus Brasil, Biolab Sanus Farmaceutica, Canbex Therapeutics, DAEWOONG, Emcure Pharmaceuticals, Endo Pharmaceuticals International, Evolus, Fresenius Kabi, GlaxoSmithKline, INSYS THERAPEUTICS, Johnson & Johnson , Lannett, Lanzhou Institute of Biological Products, LEO Pharma, Mylan, Par Pharmaceuticals, Pfizer, PhytoTech Therapeutics, Revance Therapeutics, Sun Pharmaceuticals, Takeda Pharmaceutical, and UroGen Pharma (8).

In addition, several companies in South Korea (Medy-Tox Inc.) and China (btxa) produce botulinum toxin products mainly for the Asian market. 

How does the market develop for botox products?

The human body needs three to six months to rebuild the paralyzed nerve endings. The anti-wrinkle effect wears off and the treatment must be repeated. This is how beauty patients become permanent customers. 

Promoted by the mass media the Botox boom has become a huge business with enormous growth rates. In 1993 the global sales of Allergan stood at $ 25 million. By 2001, this figure had reached $ 310 million (1). Its approval for cosmetic use increased the worldwide sales significantly. In 2005 Allergan sold Botox products for $ 831 million and in 2007 even $ 1.2 billions (9,10). Ipsen sold Dysport® for 128 million Euros in 2007 (11). 

In 2005, 43% of the BOTOX® products were used for cosmetic applications, 57% for medical purposes (9).

What are the dangers for the consumer?

There have been severe unwanted side-effects after the use of botulinum toxin products both for medical and cosmetic purposes. The toxin can spread from the site of injection to other parts of the body and can cause muscle paralysis. This can result in respiratory distress and difficulties swallowing. More than 600 unwanted side-effects and 28 deaths have been reported worldwide (8). The American Food and Drug Administration (FDA) reported further severe side-effects. Several children with limb spasticity had died after the treatment (9).

What needs to be done?

Every member of the public, every cosmetic surgeon or dermatologist needs to know that the anti-wrinkle treatment involves horrific animal suffering. The more Botox is used, the more animals have to suffer. As long as these animal experiments are still conducted, Botox products should be boycotted.

The aim of the campaign 'Stop Botox animal testing' is

  • to inform the public about these horrific animal experiments
  • to make the manufacturers to use animal-free methods instead of the mouse test
  • to remove the mouse test from the EU regulations

     

You can help!

  • Don't use Botox products
  • Spread the word
  • Write to the manufacturers asking them to speed up the validation and implementation of animal-free methods.

Further information

Further information in German: www.botox-tierversuche.de
 

 

References:

(1) K. Botrill: Growing old disgracefully: The cosmetic use of botulinum toxin. ATLA 2003; 31: 381-391 
(2) S. Bitz: The Botulinum Neurotoxin LD50 Test – Problems and Solutions. ALTEX 2010; 27 (2): 114-116  
(3) Katy Taylor, Corina Gericke, Laura Rego Alvarez: Botulinum toxin testing on animals is still a Europe-wide issue. ALTEX 2019; 36(1): 81-90 
(4) Allergan Receives FDA Approval for cell-based in vitro-assay for BOTOX. Invitrojobs.com, 28 June 2011 (retrieved 3 June 2019)
(5) Ärzte gegen Tierversuche: Großer Erfolg bei Botox-Tierversuchen, Press release 23 Nov. 2015
(6) Ipsen’s Cell-Based Assay Receives Approvals in The E.U. and Switzerland for its Botulinum Toxin. Ipsen Press Statement 27 August 2018 (retrieved, 3 June 2019)
(7) European Pharmacopoeia 5.0, Botulinum Toxin Type A for injection, 01/2005:2113
(8) Technavio: Global Botulinum Toxin Market 2017-2021 (retrieved 22 June 2017)
(9) Allergan: Annual Report 2005, p. 8 
(10) Pharmafirma Merz will in den Botox-Markt. Der Tagesspiegel, 2 Feb 2008  
(11) arznei-telegramm 2007: 38 (9), 88 
(12) FDA News, 08.02.2008   

Updated: 5 June 2019
Dr. Corina Gericke V.D.M.