2005 ANNUAL SCIENTIFIC SEMINAR The most frequently used members of this group are lmidazolidin)ul Urea, Diazolidinyl Urea, DMDM Hydantoin, Sodium Hydro:xymethylglycinatc and Quatemium-15. They are all active against bacteria but arc weak against fungi. 4. Halogenated compounds The addition of a chlorine or iodine molecule to many compounds greatly increases their anti-fungal activity. Some of our most potent anti-fungal preservatives arc of this group. They also typically hme , cry poor water solubility and arc difficult to incorporate. In this class are Ch.loro:-..y lenol, Chlorphcnesin, DichlorobeflZ)·I Alcohol and lodopropynyl Butylcarbamate. 5. Isothiazolinoncs This class of compounds are some of the most potent presen·alivcs and are frequently used at le,·els of less than 50 ppm. There arc three major isothiazolinoncs. Methylisothiazolinone, which was just appro,·ed in Japan and the EU: Bcnzylisothiazolinonc ,, hich has not been appro,·cd : and the mixture of Methylchloroisothiazolinonc and mcth� lisothiazolinonc. 6. Quatemia Quatemia compounds all hm·c a positi,·c charged nitrogen. As a result these are pH dependent with the best activity at pH's abO\·e 7. They arc weakest against Gram ncgati,·e bacteria. They cannot be used with anionic systems. Popular prescrvati,·es in this class are: Benzalkonium Chloride, Benzethonium Chloride. He:xamidinc Diiscthionate. Polyamino Biguanide. 7. 1.2 Dials There is growing interest in this class of prcsenative although none are registered as presern1ti,·es. CH2-CH- (CHz)n-CH3 I I OIi Oil As the number of carbons increase, the solubility in water decreases and the anti-microbial activity increases. They are weakest against fungi. Most popular are the C-5.6 and 8. They are Pcntylene Gl)·col. 1,2-He:xanediol and Caprylyl Glycol. Conclusions By looking at the structure of the prcserntive, a formulator can get some idea of its activity, its solubility and finally how it can be used to preser,e formulations. When looking at preservative "cocktails", you should look to sec if the components add to the overall activity or duplicate the activity of other parts. 363

364 JOURNAL OF COSMETIC SCIENCE REGULATORY UPDATE ON PRESERVATIVES - WORLDWIDE Focus Janet Winter Blaschke International Cosmetics & Regulatory Specialists, L.L.C. Cosmetic chemists anl their companies are constantly searching for a "worldwide product" It is an understandable goal that companies have a goal of having one version of a product worldwide. Whether or not this is possible, the first stumbling block for the formulator and microbiologist is the challenge of acceptable preservatives. Companies are constantly in search of a "universal formula". Sometimes formulators will tell marketers that they have a "worldwide formula" for a product. When you hear this terminology, it is time for some additionr1I reser1rch. Each country in the world has its own regulatory system. Along with those systems come ingredient restrictions Preservatives are at the top of these lists. Preservative lists fall into three categories: 1) Positive Lists 2) Negative lists :{) Restrictive Lists Positive lists are those which communicate only which preservatives are acceptable. Negative lists are those which delineate preservatives that are not acceptable under any circumstances. Restrictive lists document which preservatives are acceptable, but only under certain circumstances. Ofl en these Hre restrictions on percent.r1ge limits of use of the actual ingredient,' or components of that ingredient, and types of use, such as leave-on products or rinse-off products Preservatives are significant in that they have specific biological activity for their intended purpose. This functionality increases the scrutiny of the products, especially by governments ancl sometimes by consumer groups as well. These can often, rightly or wrongly, bear fruit in regulations that are designed to protect the health of consumers. !\Jany of the preservatives that arc currently in use have been used for decades. With the advent of different scientific approaches, and histor)· of use, some of these long-standing ingredients are under scrutiny. The world is continuing to shrink. However, that does not mean that things are getting simpler. It only means that there is more information that is shared for the governments to analyze. In the U.S. Regulatory landscape, FD.:-\ requires Lhe producers of finished product to assure the products' safety for use by the consumers. This is true for Cosmetics and Over­ t he-Counter (OTC) Drugs. In the European Union, there is a different approach. Acceptable preservatives are listed in a Positive list. This list is also a restrictive list., such that it defines certain use conditions for the ingredients. This can include specific products (for eye makeup only), product usage (not for use in products that are dispensed in aerosol form) and limits of usa�e in some or all products (e.g., 1 % in rinse-off products, 0.5 % in leave-on products). Previously the E.U. has exercised the right to put preservatives on a "Provisionally allowed" list. There can also be a Negative list which provides for preservatives that are forbidden to be used in any type of Cosmetic product. Of timely importance is the issue of safe use by the consumer by the use of date­ identifying products. l\Iost recently, the European Union enacted the Seventh Amendment to the Cosmetic Directive, which requires some kind of dating on almost all Cosmetic products. This new requirement, known as the Period After Opening (PAO) affects all