Defining Issues

The development and marketing of cosmetics and personal care products has come a long way from the days when rose water was made and sold from the back of a covered wagon. Back then, product sales were driven more by promises than by any proven benefits, and there were no regulatory mechanisms in place to guarantee product efficacy or safety. Today, the cosmetics industry is subject to government oversight and consumers have come to expect that the products they use are safe and effective.

While technological advances have spurred great innovations in product development and testing, few consumers are aware of the processes that manufacturers employ to ensure that products are safe for humans and the environment. Today, regulatory bodies around the world have set rigorous standards for product safety, while improved technology has made testing more efficient. Ongoing research continues to generate improvements in the way products are developed and evaluated from start to finish. By using the latest scientific advances and good manufacturing practices, manufacturers are putting products through cutting-edge paces designed to maximize safety. Ensuring the safety of cosmetics and personal care products is a top priority in the beauty care industry.

Advances in Science

Protecting Human Health

Before a product can appear on store shelves, it must be demonstrated to be safe to use. A key step in ensuring product safety is the process of risk assessment, whereby risk is defined as a measure of the likelihood that an adverse effect will occur under a given set of conditions. The concept of risk assessment incorporates consideration of the likelihood of exposure to a potential hazard, as well as the type and severity of the hazard.

In the cosmetics and personal care products industry, risk assessment starts with a review of the available safety data, including previous testing and history of use; information from public online databases, such as those maintained by the US Centers for Disease Control and Prevention (CDC), and the Environmental Protection Agency (EPA); information from suppliers; and results from expert scientific review groups such as the EU Scientific Committee on Consumer Products (SCCP), and the Cosmetic Ingredient Review (CIR) Expert Panel, an independent body of scientists established in 1976 by the Cosmetic, Toiletry, and Fragrance Association (CTFA) in cooperation with the US Food and Drug Administration (FDA). As of 2006, the CIR has reviewed over 1,200 common ingredients that are used in more than 100,000 marketed cosmetic products. According to the CIR, roughly 90% of reviewed ingredients may be used safely, either as currently used or with some limitations. About 10% carry an "insufficient data" designation, meaning that there were insufficient published data available to the CIR Expert Panel to make an assessment.1 In many of those cases, companies may have data in their files to substantiate the safety of an ingredient, but may have elected not to share their data publicly (eg, for trade secret reasons).

Next in the human health risk assessment process comes hazard identification, wherein any potential adverse effects that could be caused by a new ingredient are identified. Hazard identification may entail the evaluation of a variety of safety endpoints, including (but not limited to) systemic toxicity (short- or longterm), neurotoxicity, developmental and reproductive toxicity, mutagenicity, carcinogenicity, eye and skin irritation, and skin allergy. These data enable identification of an ingredient's critical adverse effects, and aid in the design of dose-response studies to calculate a value such as a NOAEL (No Observed Adverse Effect Level) for that ingredient. The NOAEL is the highest dose at which no adverse effects were seen in the safety studies.

The next step in the human health risk assessment process is exposure assessment, whereby the use of a product is studied to calculate a consumer's actual exposure to the ingredient. The beauty industry goes to great lengths to understand exactly how consumers will use a new product. For most beauty care products, exposure assessment focuses on how much of an ingredient is applied to, penetrates, and is absorbed by the skin.  The final step in human health risk assessment is risk characterization, or the integration of information obtained thus far to determine an acceptable level of human exposure. A common approach to risk characterization is to determine the margin-of-safety (MOS). MOS quantifies the risk and allows toxicologists to make a decision as to whether an ingredient is safe for use in a particular product, and is calculated via the following equation:

MOS = NOAEL/expected human exposure/uncertainty factor

Safety Never Stops: Industry Techniques for Ensuring Ongoing Safety

Safety vigilance does not stop once a product reaches market. Companies conduct extensive postmarketing surveillance and tracking of consumer comments, including the establishment of toll-free "800" numbers for consumers to report adverse reactions. Additionally, manufacturers frequently share information to ensure that all companies have full access to relevant safety information. Much of this information sharing takes place at meetings and workshops conducted by organizations such as the CTFA, the Society of Cosmetic Chemists, the International Federation of Societies of Cosmetic Chemists, and the American Society for Microbiology.

Protecting the Environment

Advances in environmental knowledge have helped improve the field of ecotoxicology, the study of how chemicals affect the environment and the organisms living in it. This discipline typically employs a tiered approach for assessing a cosmetic ingredient's chemical structure to predict its fate and effect on the environment. Under the tiered approach, screening-level tools are used initially, and more sophisticated tools are employed as needed. This approach allows companies to eliminate early in the product development cycle those compounds that will never make it to market for environmental safety reasons, and to quickly identify less toxic, more rapidly degradable compounds.

Equations known as quantitative structure property relationships (QSPRs) and quantitative structure activity relationships (QSARs) are examples of first-tier tools for estimating exposure and hazard to the environment. In addition to being quick and inexpensive to use, QSPRs and QSARs can enhance the understanding of a molecule's toxicity and biodegradability before any data are generated in the laboratory.2,3

QSARs are equations that help to predict the toxicity of a new chemical structure form its similarity in physical or chemical properties to other well-known compounds. They are quick and inexpensive to use. The graph above shows a correlation between chemical solubility and toxicity for a class of chemicals that can b used to estimate the toxicity of new chemicals from that class.

The highest tier of ecotoxicity testing uses model ecosystems, or "mesocosms." Mesocosms, which contain a diverse array of species and are sustainable for long periods of time, enable study of the environment under realistic and carefully controlled conditions, yielding enhanced understanding of a molecule's shortand long-term toxicity.

One way that the industry examines environmental safety is to set up model mesocosms, like the experimenal stream pictured here. These enable the study of the environment under realistic and carefully controlled conditions, yielding enhanced understanding of a molecule's short- and long-term toxicity.

Regulation of Cosmetic Products

By law, every cosmetic or personal care product on store shelves must be safe. In the US, cosmetics are regulated under the 1938 Food, Drug and Cosmetic Act and its amendments, which is enforced by the FDA. Historically, there has been little need for the FDA to use its regulatory authority over cosmetics, as most companies use safe ingredients and have acted voluntarily to prevent safety problems. Similarly, in the European Union (EU), cosmetics fall under the regulatory purview of the 1976 EU Cosmetics Directive and its amendments. In both the US and the EU, there is no requirement for premarket review or approval by a government regulatory body. However, in both regions, the manufacturer or distributor of a product is responsible for ensuring that it is safe for its intended use.

In most countries outside the EU and US, regulatory control for the safety of cosmetics and personal care products is generally accomplished through premarket registration and approval. A number of countries are transitioning from the premarket registration requirement toward notification and postmarket surveillance systems. Many of these countries have "negative" (ie, prohibited) and "positive" (ie, approved) ingredient lists for cosmetics-often patterned after such lists in the EU, US, and Japan.

The Role of Global Industry and Government Regulatory Groups in Review and Regulation of Cosmetic Products

Industry trade associations and government regulatory agencies are another key source of safety information for cosmetics and personal care products. These groups disseminate information through activities such as issuing safety standards and reviews, promoting alternative methods to animal testing, and publishing general safety research findings in the peer-reviewed scientific literature.

Examples of such groups include:

• United States Food and Drug Administration (FDA)-www.fda.gov
• Cosmetic, Toiletry, and Fragrance Association (CTFA)-www.ctfa.org
• Cosmetic Ingredient Review (CIR)-www.cir-safety.org
• Environmental Protection Agency (EPA)-www.epa.gov
• Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)-http://iccvam.niehs.nih.gov/Europe
• European Cosmetic Toiletry and Perfumery Association (COLIPA)-www.colipa.com
• EU Scientific Committee on Consumer Products (SCCP)-http://ec.europa.eu/health/ph_risk/committees/04_sccp/sccp_opinions_en.htm
• European Centre for Validation of Alternative Methods (ECVAM)-http://ecvam.jrc.it
• European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC)-www.ecetoc.org
• Research Institute for Fragrance Materials (RIFM)-www.rifm.org7

Biological Facts

A Sense of Preservation

Manufacturers must develop products that are not only safe as manufactured and sold, but also once a consumer takes them home and begins to use them. Preservatives help keep products safe to use whether they have been stored in a hot car or a damp shower.

Any cosmetic or personal care product that contains water has the potential to support the growth of microorganisms (eg, bacteria and fungi such as molds and yeasts). While some cosmetics (ie, those containing more than about 10% ethanol, propylene glycol, glycerol, etc, and cosmetics in self-pressurized containers) are self-preserving, most other products contain preservatives-ingredients that help to prevent or inhibit microbial growth.

Many consumers are unaware of the potential risks of contamination from unintended uses of cosmetic products. For example, diluting shampoos with tap water can compromise preservative efficacy while introducing potentially harmful microbial contaminants into the product.4 Regardless of whether a cosmetic becomes contaminated during manufacture or consumer use, the hazard is twofold, namely, (1) the direct effect of microorganisms on human health, and (2) the indirect effect on human health due to the potential for product contamination and spoilage, product separation, or formation of harmful microbial metabolites.

Potential Sources of Microbial Contamination

The complexity of processes by which cosmetic ingredients are developed, combined, packaged, and dispensed has given rise to the field of cosmetic microbiology. This scientific discipline is dedicated to finding and preventing the growth of microorganisms in beauty products, and focuses primarily on (1) production hygiene to protect products during manufacturing, and (2) preservative ingredients to ensure product microbial safety in the hands of consumers.5

The great diversity of intended cosmetic uses requires a holistic approach to preservation, one that considers all aspects of product development from concept and design through manufacturing to the last consumer use before disposal. Once packaged in final product form, cosmetic units are expected to remain stable through wide variations of temperature and humidity, in distribution, and ultimate consumer acquisition and storage (eg, from hot cars to damp and wet bathrooms and showers).

Preservatives also play an important role in preventing oxidation, which can compromise cosmetic efficacy and aesthetics. That is why it is important to discard products that change color or smell, and to heed any expiration dates that may appear on product packaging (Note: In the US, expiration dates are not required on cosmetic products, only on products that are classified as cosmetic drugs, such as antidandruff shampoos and antiperspirants).

Defining Skin Sensitivity

A key consideration when evaluating the safety of a cosmetic product is whether it irritates the skin or eyes, and why that irritation occurs. The issue is complicated by differences in how individuals react to ingredients and in the type of responses. Some responses are objective in nature and can be measured via instrumentation or visual grading. However, many responses are purely subjective and are more difficult to measure.6 A prime example is what consumers may describe as "sensitive skin." Far from being a rarity, consumer studies in all races suggest that from 25% to 50% of the global adult population may experience heightened skin sensitivity.7 However, there is usually considerable disparity between the incidence and severity of "sensitive skin" conditions that are self-diagnosed by consumers vs those diagnosed by physicians.8

Sensitive skin, also referred to as sensory skin irritation, chemosensory irritability, cosmetic intolerance syndrome, or status cosmeticus, is a condition that can generally be defined as a heightened intolerance to topically applied substances, such as cosmetics or personal care products. Neurosensory symptoms such as itching, burning, stinging, tingling, and tightness are characteristics of the condition and frequently are experienced on the face. Typically, these symptoms are apparent immediately after product use; however, they can be delayed minutes to days after product use, and exacerbated by wind, sun, excessive heat, humidity, or cold temperatures.9 Roughly 50% of patients with sensitive skin demonstrate such uncomfortable symptoms without accompanying visible signs of inflammation.10

The diagnosis of sensitive skin depends upon many factors, including inherited factors, gender, age, and race. Nevertheless, it is clear that individuals with sensitive skin appear to have several unique skin attributes that affect their immune system and the skin barrier, making them more susceptible to irritation. Dermatologists define sensitive skin as reactions characterized by redness, pustules, bumps, and, at times, erosions. Those suffering from atopic dermatitis, eczema, allergic contact dermatitis, irritant contact dermatitis, seborrheic dermatitis, rosacea, acne, and psoriasis may have a predisposition to this condition.11,12

As a result, over the past 10 years, there has been an increase in the demand for (and manufacture of) cosmetics and personal care products formulated for individuals with sensitive skin. While there are a large number of sensitive skin products on the market today, there is currently no industry-wide or government standard for characterizing the condition or for substantiating sensitive skin product claims. This may be attributed to the lack of full understanding of the underlying mechanisms leading to sensitive skin.13 While great strides have been made in the study of sensitive skin, more research is needed to fully explain this condition. An example of how P&G Beauty has approached this issue can be viewed in the sidebar discussion of Head & Shoulders® Sensitive Formula on the next page.

Lab Notes

Standards in Product Testing

The human repeat insult patch test (HRIPT) is widely used to confirm the absence of skin sensitization potential.

Occasionally, ingredients that are safe by themselves may interact with another ingredient to produce effects that may be deleterious. New combinations of ingredients, even when all the ingredients are well known, may need to be tested for skin irritation or sensitization potential. A large number of testing protocols have been developed specifically to test ingredients for such endpoints. While in vitro (ie, test tube or "in glass") test methods may be used in the initial evaluation process to predict skin irritation potential, clinical testing with human subjects is often conducted in the final stages to confirm the product's mildness to skin. Most finished product formulas are clinically tested in humans to ensure safety and efficacy under normal conditions of use. However, in order to ensure an adequate margin of safety, testing may be conducted under conditions that exaggerate potential exposure.

Another important part of product safety assessment is the need to confirm the absence of any potential for development of an allergic response (also known as sensitization). A sensitization reaction is more serious than a transient irritation reaction, as the development of an allergy is irreversible. Clinical models, such as the human repeat insult patch test (HRIPT), are widely used to confirm the absence of skin sensitization potential. Additionally, as sunlight is known to exacerbate allergic responses in some instances, companies often employ photosensitization test protocols that combine exposure to an ingredient or product with exposure to light under controlled conditions.

All of these testing methods conform with international ethical standards for clinical testing to ensure: (1) that protocols involving human use are reviewed by independent third parties, such as institutional review boards or an independent ethics committee; (2) that medical oversight of the research is appropriate and conducted by scientifically qualified persons; and (3) that all volunteers understand the benefits and risks of the study before deciding whether to participate.14

Skin Safety Claims

In addition to ensuring that their products are safe from skin irritation and sensitization, companies often make safety claims that can be found on a product label.  Although the cosmetics industry is highly regulated, there is no consistent set of guidelines or definitions governing the use of claims such as "hypoallergenic," "safe for sensitive skin," or "mild on skin."

Moreover, manufacturers are not required to substantiate such claims with the FDA.15,16  Nevertheless, most companies have internal guidelines for validating product claims through processes such as human clinical studies, or through consumer-panel testing under highly controlled conditions.

Substantiating Sensitive Skin Claims: The Case of Head & Shoulders Sensitive Formula

Consumer research indicates that many dandruff sufferers with self-perceived "sensitive scalp" do not regularly use antidandruff shampoos because of a perceived harshness of these products to the scalp. Consequently, Procter & Gamble (P&G) Beauty developed the Head & Shoulders (H&S) Sensitive formula as a variant to the "dry scalp" formulation and put it through the following steps to ensure that it could meet the sensitivity claims:

1) The new formula, which incorporates the active ingredient zinc pyrithione (ZPT) (recognized under the FDA's over-the-counter [OTC] monograph process as "safe and effective for the treatment of dandruff") was further modified to improve the mildness profile and reduce potential irritants such as colorants and perfumes.

2) A number of clinical studies were conducted to demonstrate that the formulation does not exhibit skin irritation or sensitization among consumers with self-perceived sensitive skin/scalp. These included 48-hour patch tests on normal subjects and on subjects sensitive to lactic acid (a clinical marker for sensitive skin), a safety-in-use study on self-perceived sensitive skin subjects, and HRIPT tests on both normal subjects and self-perceived sensitive skin subjects. No skin irritation or sensitization was observed in any of these studies.

3) These data were reviewed by two international expert panels on products intended for application on sensitive scalps. The panels concurred with the assessment that the H&S Sensitive Formula was well tolerated by subjects with self-perceived sensitive scalp, had the same skin tolerance profile as a control with established clinical and in-market skin mildness, and would not be expected to induce skin sensitization in the general population (including those with self-perceived sensitive skin).17

Emotional Attitudes and Behaviors

Safety Matters

Most consumers around the world feel confident that the cosmetic products they use and the ingredients in these products are safe.

Research indicates that the vast majority of consumers feel that the cosmetics and personal care products they use are safe.18 There is an ongoing attempt by certain activist groups, however, to erode this confidence with media coverage that would have consumers believe that the products they use contain large numbers of ingredients that can harm their health.19 Such allegations are not supported by scientific evidence. Yet, media coverage can be negative and sensational, often appealing to consumers' fears by focusing on toxicity potential (ie, hazard) alone, without any regard to actual risk (which must also consider potential for exposure, as discussed earlier in this document). It therefore behooves the beauty industry to be more proactive and transparent in the sharing of information on the safety of cosmetics and personal care products and their ingredients and the processes we use to ensure their safety. To that end, the CTFA has instituted a Consumer Commitment Code for its members. Highlights of the new code, which formally took effect on January 1, 2007, include20:

• Incorporating and strengthening some practices already in place for most companies, such as the current voluntary reporting of product formulas and manufacturing establishments to the FDA
• Establishing new practices such as a safety information summary program that "makes information relevant to cosmetic product and ingredient safety readily available to the FDA upon request" and creating a cosmetic ingredient information website for consumers
• Continuing close collaboration with the FDA and state regulatory agencies "to provide as much information regarding cosmetic safety as consumers want and need in order to make fully informed choices when purchasing cosmetic products"

When Public Interest Groups, Media and Cosmetic Ingredients Mix: The Controversy Over Phthalates

Phthalates are ingredients that are sometimes used at low levels in cosmetics and personal care products because they deliver benefits that are difficult to achieve otherwise. For example, adding some dibutyl phthalate (DBP) provides just enough "give" to make nail polish flexible and chip-resistant. Also, when perfume fragrance ingredients are dissolved in diethyl phthalate (DEP), they evaporate more slowly, allowing the scent to linger longer on the skin. In 2000, a CDC report suggested that phthalate levels in human urine samples were higher than expected and that levels of DBP were higher in women of childbearing age than in women who were not.21,22  Although the authors cautioned that the size of the sample was small and not representative of the general population, and that the mere presence of these ingredients in the bodies of consumers did not imply a biological risk, the report was seized upon by public interest groups in a media campaign denouncing the use of DBP in cosmetics and personal care products. However, the campaign produced no evidence that human exposure to DBP even approached what would be considered dangerous levels.

In a 2003 follow-up report, the CDC showed that levels of exposure to DBP and DEP were not only within predicted levels but also well within the safety levels set by the EPA. In fact, the data showed that the average exposure levels for DBP remained more than 100 times below government safety levels.23 A separate analysis of data from women aged 20 to 39 years showed that their levels of exposure to DBP were slightly lower than for other women, not higher.24 The US National Toxicology Program's Center for the Evaluation of Risks to Human Reproduction concluded that DBP poses minimal risk to reproduction or fetal development.25,26 In addition, the FDA concluded that it "...does not have compelling evidence that phthalates, as used in cosmetics, pose a safety risk" and that there is "no reason for consumers to be alarmed at the use of cosmetics containing phthalates."27 Finally, a comprehensive re-review of all available safety data on phthalates by the CIR Expert Panel in 2003 pronounced DEP and DBP safe for use in cosmetics.28

Despite the fact that there is no reliable evidence that phthalates found in cosmetics have ever caused harm in any human, many companies have eliminated DBP from their products in order to comply with the new EU ban on its use in cosmetics (which does not take into account exposure conditions). This example demonstrates how misleading reporting by the media and activist groups can ultimately deprive consumers of potentially useful cosmetic ingredients.

Reading the Fine Print: Consumer Perceptions of Product Labels and Labeling Regulations

Reading the labels of cosmetic products, with their longingredient names, leaves many consumers perplexed. By law, the cosmetic labels must carry a listing of theInternational Nomenclature for Cosmetic Ingredients (INCI) chemicalnames of a product'singredients. The INCI, an international system for naming ingredients used in cosmetic products, helps to minimize confusion that might arise if various synonyms for chemical names are used. By standardizing the ingredient nomenclature, the INCI also assists physicians in the diagnosis of possible cosmetic-related skin conditions and facilitates the patch testing procedures that may be needed to identify suspect ingredients early in patient evaluations.

Animal Testing: Myths, Facts, Advancements

In the past, scientific and legal requirements meant that safeguarding consumers' health invariably involved the use of animal research. Today, governments tell us that it remains impossible to avoid all research involving animals and maintain the same levels of health protection. At the same time, some of our consumers tell us they want to see more progress on alternatives to animal research. The beauty industry, therefore, works with interested partners in the scientific and academic communities to develop alternatives that offer the same level of health protection as current animal-based research, and helps to promote their acceptance.

Manufacturers are also working with governments around the world to challenge the remaining legal requirements for research involving animals and to find other options wherever possible. In this way, the industry will work to limit and ultimately eliminate animal research for cosmetic and personal care product ingredients.

Consequently, many manufacturers strive to use alternative methods such as computer models, in vitro cell culture tests, advanced chemistry methods, published scientific studies, and the information consumers provide about the products they use, and conduct limited research involving animals only as a last resort. In the rare cases in which animal tests are considered necessary, or are requested by regulatory bodies, companies work closely with animal welfare agencies and go to great lengths to ensure that the animals receive the best available care.

One of the most potentially misleading claims in consumer marketing today is the phrase "Not Tested on Animals." When this phrase appears on a product package, the consumer has no way of knowing if the statement applies to the product, its ingredients, tests by the manufacturer or its suppliers, or even if the claim applies only to tests conducted after a certain date. It is important to note that the safety information for most ingredients that are commonly used in cosmetics or personal care products today was developed, at some point in time, from previously conducted animal studies. Currently, most countries have no regulations or guidelines that stipulate the conditions that must be met in order to make a valid "not tested on animals" claim. The exception is in Europe, where in 2006 the EU issued a set of guidelines that provided the following clarifications:

"...‘no animal tests have been carried out' means that no animal test whatsoever was carried out in relation to the development or safety evaluation of a cosmetic product or its ingredients. Only the full replacement of the animal tests by an alternative method, and therefore not a reduction or a refinement of animal tests, allows the claim to be made. Furthermore, it does not matter where the test (including re-testing) is performed (in the EU Community or in third party countries) or when the test has been performed."30

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