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Repost: Comprehensive Guide to Preservatives in Cosmetics. Currently, there are over 60 types of preservatives used in personal care products worldwide, but even fewer of these are widely and commonly utilized. Here, the type refers to the chemical structure of the preservative, not the product name given by the supplier; many so-called new products are merely combinations of different preservatives in varying proportions. 1. Definition of preservatives: In simple terms, preservatives are substances that can prevent the growth of microorganisms. In cosmetics, preservatives serve to protect the product from microbial contamination and extend its shelf life ； Ensure the safety of products to prevent consumers from suffering potential infections due to the use of microbiologically contaminated products. Cosmetics deteriorate due to microbial contamination, and generally, this can be detected by their appearance. Molds and yeasts often cause mold spots in areas such as the edges of product packaging ； Products contaminated by microorganisms may exhibit turbidity, precipitation, color changes, pH shifts, foaming, and altered taste; in the case of emulsions, demulsification and clumping may occur. If insufficient amounts of preservatives are added, microorganisms may adapt to their surrounding environment and develop resistance, thereby rendering the preservative ineffective. 2. Mechanism of action of preservatives: The survival and reproduction of microorganisms in cosmetics depend on certain environmental factors: physically, these include temperature, environmental pH value, osmotic pressure, radiation, and hydrostatic pressure ； In terms of chemistry, these include water sources, nutrients (sources of C, N, P, S), oxygen, and organic growth factors. Based on this, the mechanism of action of preservatives can be briefly summarized as follows: 1) In products such as ointments with very low water content, microorganisms generally find it difficult to grow ； 2) For most bacteria, the optimal pH range for growth is near neutral (6.5–7.5); strong acids and strong bases are not suitable for microbial growth. For example, common fruit acid-based products usually have a better preservative effect compared to neutral products ； 3) Increasing or decreasing osmotic pressure can lead to the rupture of cell membranes, as well as membrane contraction and dehydration ； 4) Additionally, surface tension is also one of the factors that affect microbial growth; in formulations with high concentrations of certain surfactants, it is difficult for microorganisms to grow. In this regard, cationic surfactants exhibit a significant effect, while anionic and non-ionic surfactants have little physiological toxicity toward microorganisms. 5) Under normal conditions, the optimal temperature for bacteria to grow is between 30°C and 37°C, while for molds and yeasts it is between 20°C and 25°C. Therefore, high-temperature disinfection methods can be used. However, certain spore-forming bacteria form a protective membrane once they adapt to their environment, making it impossible to kill them even at high temperatures of 80°C to 90°C for a short period of time. The effect of preservatives on microorganisms occurs only when they are in sufficient concentration and in direct contact with the microorganisms. Preservatives first come into contact with the extracellular membrane, adhere to it, pass through the cell membrane to enter the cytoplasm, and only then can they exert their therapeutic effects in various locations by preventing cell reproduction or killing the cells. In fact, it is mainly the effects of preservatives on the cell wall and cell membrane, as well as their impact on the activity of enzymes that influence cellular metabolism or on the structure of genetic particles in the cytoplasm. 3. Classification of preservatives: Most preservatives work by coming into contact with the cell membrane and reacting with certain components of the cell wall, primarily proteins, thereby destroying the protective structure of microbial cells or interfering with their metabolism and disrupting their normal growth process, thus achieving a preservative effect. Cations, on the other hand, kill microorganisms by affecting their osmotic pressure, causing the cell membrane to rupture, leading to contraction and loss of water. Based on the dozens of preservatives commonly used in the cosmetics industry today, they are classified according to their active ingredients. 1) Imidazolidinyl ureas: ISP’s Germall 115, Germall II, Germaben II-E, Germall Plus, Germall IS-45. In the Gemeyi series, the main component is imidazolidinyl ureas, which acts as a formaldehyde donor; it achieves bactericidal effects by slowly releasing formaldehyde during use. The main component of Germall 115 is imidazolidinyl urea, and its antibacterial activity is inferior to that of Germall II (bis-imidazolidinyl urea). Germaben II-E is a mixture of parabens, and it has an advantage over single-component agents in combating molds and yeasts. Germall plus and Germall IS-45 are mixtures of iodopropynylbutylmethylamine esters, and they have received positive feedback from the market. However, it is important to avoid any ingredients in the formulation that might inhibit their activity. Additionally, 1% iodopropynylbutylmethylamine ester has poor water solubility; therefore, if an organic solvent is not used for dissolving it during use, this could affect its preservative effects. The Germall IS-45 is a newer variant sold by ISP Company, containing 5% methylparaben, which enhances its ability to inhibit molds and yeasts. 2) Cycluril: LONZA’s glydant plus, DMDMH; NIPA’s DMDMH. Products of this type are also formaldehyde donors. Glydant Plus is a mixture of iodopropynylbutylmethylcarbamate, with a content of 5% of iodopropynylbutylmethylcarbamate. In addition, LONZA also offers Liquid Glydant Plus (a propylene glycol solution) with an alleged active ingredient content of 50%; it should be noted that components such as reducing agents in the formula may have an inhibitory effect on it. 3) Thiazolinones, as well as Kathon CG and 950 from Rohm and Haas, isocil PC from LONZA, and EUXYL K100 and EUXYL K727 from S&M. Products of this type are also formaldehyde donors. LONZA’s isocil PC is composed of two types of isothiazolinones; 23% magnesium salts are added to the formula to enhance its effectiveness, primarily by altering the osmotic pressure. K727 is a compound of methyl dibromoguanidine. EUXYL K100, on the other hand, is a mixture of benzyl alcohol, and it also possesses considerable antiseptic properties for the gas phase portion. 4) Parabens (p-hydroxybenzoates): Zhejiang Shengxiao, ISP’s Liquapar Oil, S&M’s EUXYL K300, NIPA’s Phenonip, etc. These types of preservatives are among the most widely used ones at present, but they require relatively large amounts. As the carbon chain length increases, their water solubility gradually decreases, which affects their distribution rate in aqueous solutions. Its anti-mold effect is quite prominent. Methyl paraben has the best water solubility and can often be added directly to the aqueous phase ； Ethyl, propyl, butyl, and isobutyl parabens, on the other hand, tend to dissolve in the oil phase. Methyl paraben is a preservative suitable for acidic environments; it exhibits a maximum antibacterial activity of 77% at pH 5, 63% at pH 7, and around 50% at pH 8.5. Therefore, the activity of parabens in the system can be improved primarily by lowering its pH, usually to 7.0–6.5 or lower, although sometimes they can also maintain their efficacy in systems with a slightly higher pH. 5) For quaternary ammonium salts-15, the only product currently available is Dowicil 200 from Dow Chemical Company. Dowicil 200 does not dilute formaldehyde, but its antioxidant and redox capabilities are better than those of Gemey from ISP Company. In some formulations that are prone to discoloration, it is common practice to add a small amount of sulfite as a preventive measure. 6) Domestic Kaisong-CG (with the same chemical structure as Category 3): CY-1 from Zhejiang Shengxiao, MD-2000 from Shandong Mingda, Xinke-99 from Jiangsu Xinke, KS-1 from Shaanxi Huarun, and XF-1 from Xi’an Xianfeng. Products of this type are also sources of formaldehyde. It is sensitive to pH levels in terms of usage; it provides excellent preservative effects in acidic environments, and only a small amount is required – around 0.08% – to achieve good results. However, in an alkaline environment, it loses its preservative activity. In such products, magnesium salts are added to enhance their anti-corrosion properties and to increase their osmotic pressure; therefore, when using these products, it is necessary to consider the compatibility between the various ingredients to avoid precipitation, especially in transparent products, where great care must be taken. In addition, amines, thiols, sulfides, sulfites, and bleaching agents can also inactivate caisine. 7) There are also preservatives such as benzoic acid/benzyl alcohol and their derivatives, as well as alcohol-based preservatives. Among these, phenoxyethanol is a representative example; it is an excellent solvent and preservative that is often used in the formulation of preservatives as a solvent to dissolve other oil-soluble preservatives. However, since it can also function as an emulsifier, its impact on the product itself must be taken into consideration when using it. It is also important to note that phenoxyethanol becomes unstable under certain high pH conditions. 8) Benzoic acid/sodium benzoate/sorbic acid potassium. Benzoic acid/sodium benzoate/sorbic acid potassium are mainly used in the food industry, so they are listed together. Its mechanism of action as a preservative is as follows: Benzoic acid-based preservatives exert their effect through their undissociated molecules. Undissociated benzoic acid has strong lipophilicity, allowing it to easily pass through the cell membrane and enter the cells. It interferes with the permeability of the cell membranes of microorganisms such as molds and bacteria, hindering the absorption of amino acids by these cell membranes. Once inside the cells, the benzoic acid molecules acidify the alkaline substances stored within the cells, thereby inhibiting the activity of respiratory enzymes in microbial cells, thus serving as a preservative. These preservatives also belong to the category that are effective in acidic environments; sorbic acid and benzoic acid are inactive at pH 7, but exhibit activities of 37% and 13% respectively at pH 5, therefore they should be used in slightly acidic media. 9) Bronopol: Bronopol is short for 2-bromo-2-nitro-1,3-propanediol. It possesses broad-spectrum antibacterial properties and can effectively inhibit most bacteria, with particularly strong effects against Gram-negative bacteria. It is unstable under high temperature and alkaline conditions, and its color darkens under sunlight. Bropol can be used in combination with most surfactants, but the presence of substances containing -SH groups in cosmetic ingredients, such as cysteine, reduces Bropol’s antibacterial activity. Furthermore, metallic aluminum can also reduce the antibacterial activity of brobopol. 10) IPBC: The English name for IPBC is 3-iodo-2-propynyl-butyl-carbamate; its main component is butyl carbamate of 3-iodo-2-propynyl. It possesses broad-spectrum antibacterial activity, especially showing a strong inhibitory effect on molds and yeasts. It has good compatibility and can be mixed with various components present in cosmetics. Test results show that its antibacterial capacity is not affected by additives such as surfactants, proteins, and traditional Chinese herbs in cosmetics. 11) Triclosan: The INCI name for triclosan is Triclosan, and it can be used as a preservative in low concentrations. At high concentrations, it exhibits a broad and potent killing and inhibitory effect on infectious agents as well as pathogenic Gram-negative bacteria, fungi, yeasts, and viruses (such as hepatitis A and B viruses, rabies virus, and HIV), which is why it can also be used in disinfection products. At high concentrations, when used as a bactericide, its mechanism involves directly destroying the bacterial cell membrane, causing irreversible denaturation of proteins and nucleic acids in the cytoplasm, which leads to the leakage of low-molecular-weight intracellular substances and the death of the bacteria. At low concentrations, it is used as an antibacterial agent; its mechanism involves acting on the bacterial cell membrane to prevent bacteria from absorbing nutrients essential for their growth, such as amino acids and uracil, thereby inhibiting bacterial proliferation. This effect can be achieved at extremely low concentrations, namely the MIC. There are a vast number of preservatives, too many to list all; here are those that are commonly used in the cosmetics industry. In general, most preservatives are sensitive to strong redox chemicals, as they interfere with cellular metabolism and damage cell structure by undergoing chemical reactions with various targets within microbial cells. Quaternary ammonium salts, among others, act as preservatives by affecting the osmotic pressure of microbial cells. When using preservatives, it is necessary to consider the impact of each component in the formula on the preservative, so as to enable it to exert its maximum effect. 4. No preservatives added: With the advancement of scientific research, there has been increasingly in-depth study of the safety of preservatives, and it has been shown that many traditionally used preservatives have certain negative effects. Therefore, the concept of safe, “additive-free” preservative-free products, which has been introduced from Japan over the years, has been very popular in the market. It has not yet become fully widespread solely due to technical reasons. However, if one day formulators manage to solve the antimicrobial issues associated with preservative-free systems, it is believed that products without additives will account for a larger share of the market. Concerns regarding preservatives include: DMDMH: worries about the release of formaldehyde ； Casson series: Contains chlorine, which may be irritating to certain skin types ； Bropol: May lead to the formation of the carcinogenic substance nitrosamine ； IPBC: May lead to iodine intake ； Nephenates: In recent years, there has been increasing interest in nephenates, focusing mainly on two aspects. Firstly, the benzene ring of parabens can be detected at extremely low concentrations, and since they are lipophilic, some accumulation may occur in adipose tissue. Another point is that preservatives such as parabens, particularly butylparaben, have been shown in specific testing systems to possess a certain ability to mimic the female hormone estrogen. From methyl paraben to butyl p-hydroxybenzoate and butyl isohydroxybenzoate, estrogenic activity increases with the length of the hydrocarbon chain. Of course, there is also an argument that parabens are functional esters that can be easily hydrolyzed by enzymes present in living tissues, so they do not have any impact on human safety or physiological systems. Triclosan: It has been proven to be a substance with negative effects on the environment ； 5. Compatibility of preservatives: Generally speaking, a particular preservative is effective in killing or inhibiting only certain types of bacteria; therefore, for the reasons outlined below, it is necessary to conduct research on the combination of preservatives in cosmetic formulations. 1) Broadened antibacterial spectrum: One preservative is effective against some microorganisms but less effective against others, while another preservative has the opposite effect. When used together, they can achieve the goal of broad-spectrum antibacterial prevention and treatment. 2) Enhanced efficacy: When two preservatives with different bactericidal mechanisms are used together, their effect is not merely a simple addition but rather a multiplicative one; typically, sufficient bactericidal activity is maintained even at reduced usage levels. 3) Resistance to secondary contamination: Some preservatives are effective in killing mold and fungal microorganisms, but their effect lasts only for a limited time. Other preservatives have a weaker killing effect but exhibit a significant inhibitory effect. By using these two types together, it is possible to maintain the quality of the product during storage and on the shelf, while also preventing re-contamination during use. 4) Improved safety: When using preservatives alone, sometimes higher amounts are required to achieve an antiseptic effect than the permitted levels. By combining multiple preservatives within their allowed limits, it is possible to achieve the desired preventive effects while ensuring the safety of the product. 5) Preventing the development of resistance: If a microorganism easily develops resistance to one preservative, it is naturally much harder for it to develop resistance to two or more preservatives at the same time. 6. Chemical compatibility of preservatives: When using preservatives, it is essential to pay close attention to the compatibility between these preservatives and all the other ingredients in the system. Compatibility refers to the process by which preservatives can interact with components of the contents, packaging materials, certain substances, etc., leading to a reduction in their effectiveness or even loss of efficacy; conversely, it can also result in enhanced effectiveness. If compatibility leads to a loss of efficacy, it requires attention. The aspects listed below are for reference only; in the actual process of formulating and producing products, it is necessary to continuously accumulate knowledge, draw conclusions, and make additions in order to gain as comprehensive an understanding as possible of the chemical compatibility issues related to preservatives. 1) Certain components in cosmetics, such as carbohydrates, talc, metal oxides, cellulose, etc., can adsorb preservatives and reduce their effectiveness. 2) The product contains starch-like substances, which can affect the antibacterial effect of parabens. 3) High concentrations of proteins (amino acids) may, on the one hand, reduce the antibacterial activity of preservatives by forming a protective layer around microorganisms, and on the other hand, promote the growth of these microorganisms. 4) Metal ions such as Mg2+, Ca2+, and Zn2+ have a significant impact on the effectiveness of preservatives. Generally, excessive amounts of these metal ions can lead to the formation of insoluble compounds in fragrances, lubricants, or natural/sensitive compounds, or they can initiate catalytic oxidation reactions. 5) Preservatives can form hydrogen bonds with certain components of cosmetics (such as sorbic acid with certain components) or chelates (such as iron ions in thickeners), thereby reducing the effectiveness of the preservative system through \"binding\" or \"consumption\". 6) A small amount of surfactant can increase the permeability of cell membranes to preservatives, thereby enhancing their effectiveness; however, at higher concentrations, micelles are formed that attract the preservatives present in the aqueous phase, reducing their concentration there and affecting their bactericidal capacity. 7) Certain preservatives and surfactants, such as sulfates (esters), carbonates (esters), nitrogen-containing surfactants, pigment fluorescent dyes, and packaging materials (plastics, metals, rubber), not only affect the efficacy of the preservatives but also degrade the quality of the products. 8) Non-ionic substances as well as those with high levels of ethoxylation can affect the activity of paraben esters. 9) Sulfites, on the other hand, can impact the activity of isothiazolinones and methyl dibromoglycinate; some people might say that since their formula does not contain sulfites, there should be no problem. But remember, for example, sodium sulfite is a common raw material used as a decolorizing agent; it’s a good idea to check with the supplier of the raw materials to see if they contain sulfites. 10) Certain plastics can adsorb the activity of preservatives (such as paraben esters). Therefore, it is very important to test the product in its final packaging to ensure adequate corrosion protection. 11) The effects or potential effects of preservatives on various aspects such as the surface tension of deionized water, the foaming property of the product, the solubility of components, the color development of pigments, the aroma of flavors, and the biological activity of active factors should all be taken into consideration. As for synergistic effects, a typical example is that if the formula contains more than 15% ethanol, no additional additive is needed. Add other preservatives. Similarly, zinc oxide contained in sun protection and diaper rash formulations possesses antimicrobial properties of its own. If the content of diols in the formula is high, it can enhance the effectiveness of preservatives; by binding with free water, it can also control the environment necessary for microorganisms to survive, thereby allowing for less use of other preservatives or even eliminating the need for them altogether. Discussions on the system aspect mainly focus on issues such as whether preservatives are needed in water-in-oil, silicone oil-in-water, or water-free products. The fact is that even though we know that the growth of microorganisms relies on water, and even though we know that the external surface of these systems does not contain water, we must not overlook the moisture in the air; a small amount of moisture may remain only on the surface of the product, but this is enough to cause microbial contamination of the product. Therefore, preservatives such as phenoxyethanol, which have a certain vapor pressure and are volatile, can help prevent microbial contamination of this type. 7. Preventing process contamination: Formulators design antiseptic systems in the laboratory that meet the requirements of the system, but sometimes microbial problems arise even after the product reaches the consumers, and this is mainly due to process contamination, which disrupts the original system. Therefore, it is also necessary to be vigilant against the introduction of pollution sources during all stages of product production. Below are the areas that can be controlled. 1) Preventing contamination of raw materials There are a wide variety of raw materials used in cosmetics, including various surfactants, animal and plant oils, animal and plant waxes, fatty acids and their esters, alcohols, hydrocarbons, gums, sugars, starches, proteins, cellulose derivatives, vitamins, inorganic salts, and industrial products in the form of powders or fillers. Before entering the factory, most of these raw materials have not been sterilized and possess conditions suitable for microbial growth and reproduction. Many Gram-negative bacteria can grow well in the presence of most surfactants, while Gram-positive bacteria, particularly monococci, are often found in many cosmetic ingredients. Furthermore, the large amount of water used in cosmetics production may also introduce microorganisms into the final products. Generally speaking, the quality of raw materials largely determines the quality of the final product; therefore, it is necessary to establish testing procedures for raw materials during the production of cosmetics, set microbial standards for these materials, and employ strict sterilization and disinfection methods. Raw materials are prone to contamination during storage; therefore, moisture-proof containers should be used, and they must be used at the specified temperature and within the designated shelf life. For raw materials contaminated by microorganisms, methods such as thermal sterilization, ultraviolet sterilization, filtration for sterilization, and sedimentation for sterilization are generally used. Thermal sterilization methods are highly effective in killing common microorganisms. Water used in cosmetics is generally deionized water or distilled water, and various types of microorganisms can grow after it is stored for a few days. To ensure water quality, microbial levels in the water should be tested daily; if no significant issues are detected, the frequency of testing can be reduced, but this must be based on an effective system that has been proven to work. However, microbial testing must be conducted at least once a week on the microbial control devices in the water treatment system as well as at all points where water is used. If the test results from any particular water intake point are above the acceptable limits, a thorough analysis must be carried out until the cause is identified and decisive actions are taken to rectify it. 2) Prevention of environmental and equipment contamination The design of the air handling system in a production environment varies depending on the specific requirements of each area in the factory. It is necessary to take into account the quality of air required for operations in that area, which entails the use of several different air treatment systems; the design of these systems must be based on the air quality needed in each area they serve. The design of these systems must take into account several factors, including the quality, temperature, and humidity of the incoming air, as well as the exchange rate and the purity requirements imposed by the system design. It is also necessary to consider the location of the inlet/outlet vents, along with the layout of the ducts used to control airflow patterns. In humid areas, walls, ceilings, floors, pots and pans, stirrers, feed pipes, and utensils need to be regularly cleaned thoroughly and disinfected, as these areas are conducive to the growth and reproduction of microorganisms. Commonly used disinfectants include sodium hypochlorite, formaldehyde, chlorhexidine, povidone-iodine, and ethanol. 3) Preventing contamination of packaging Unhygienic packaging materials (barrels, bottles, lids) can cause microbial contamination of cosmetics, so they need to be cleaned before being used again. Specific packaging is one of the measures to maintain the quality of cosmetics. The effectiveness of preventing microbial contamination in storing products of the same type varies depending on their packaging type; pump-based packaging provides good results for emulsion cosmetics ； Shampoo bottles with screw caps work better than those with sliding caps. 4) Preventing contamination by operators The human skin, nose, ears, mouth, etc., are home to microorganisms. Towels, when wet, can accumulate a large number of microorganisms (including Gram-positive bacteria) over time. Therefore, good personal hygiene is an effective way to control microbial contamination. Employees who do not maintain good personal hygiene will render all the aforementioned measures ineffective. Even with the best supplies, equipment, procedures, and cleaning practices, contamination can still occur. Special cleanroom clothing, caps, and shoes must be worn, and the hands of production staff are required to be disinfected. Generally, it is first washed with soap and water, then immersed in a chlorine-based disinfectant or 75% ethanol, or disinfected using chlorhexidine and chlorhexidine acetate. 8. **Preferences: Each** has its own specific preferences or regulations regarding the use of preservatives; this does not affect cosmetics manufacturers selling in the domestic market, and it is provided only for reference. However, if there are manufacturers with export capabilities, one should seek out relevant agencies for further detailed information. 1) Annex VI of the EU’s cosmetics regulations limits the use of isotiazolinones to 15 ppm in all applications ； The Cosmetic Ingredients Review (CIR) in the United States specifies a maximum usage level of 15 ppm in rinse-off products, while the maximum level for leave-on products is 7.5 ppm ； In Japan, it is stipulated that thiazolidines can only be used in rinsing products. 2) From a legislative perspective, Japan remains the country with the strictest regulations on preservatives in cosmetics. 3) Germany and Scandinavia (a general term for Sweden, Norway, Denmark, and Iceland) do not prefer to use thiazolidine-type preservatives. 4) France pays more attention to phenoxyethanol. 5) Most European products do not use preservatives that release formaldehyde. 6) Bronopol is widely used in the UK, but the situation is the opposite in the US. 7) In Europe, methyl dibromoglycinonitrile can only be used in rinse-off products thereafter, but in the United States it can be used in both rinse-off and leave-on products. 8) European regulations consider benzyl alcohol to be an allergen present in fragrances. Last edited by zxh6267 on 2009-2-13 14:10]