The Tradition & Science of Safe Products

P&G policy on product safety Founded in 1837, Procter & Gamble is one of the largest consumer product companies in the world. In fiscal year 2007, it had annual revenue of US$ 76.4 billion, and ranked 74th on Fortune 500 list of the world’s largest corporations. P&G has operations in more than 80 countries, with more than 300 brands on market in 160 countries. These include Beauty, Household Care and Health and Well-being products. Three billion times a day, P&G brands touch the lives of people around the world.

P&G company policy statement

The Company’s products and packages will be safe for the consumers and the environment when used as intended. The Company will seek to ensure that our operations are safe for our employees, neighbours and the environment. The Company will meet or exceed all applicable legislative and regulatory requirements with respect to product safety and labelling. The Company will provide interested parties with relevant and appropriate factual information about the safety of our products and packages.

P&G product safety assurance key elements Company-wide policies on product safety applied consistently across the globe. Pre-Market, science-based assessment of product safety. Rigorous control of production from raw material specifications, formulation management, process and quality control, to QA release. Post market surveillance and rapid response.

1

The Tradition & Science of Safe Products

The Tradition & Science of Safe Products

2

P&G human safety organization, expertise and capability Overview

Our People

Human Safety has been an integral part of our commitment to our consumers since the foundation of the company in 1837. In the earliest days, the company has not only utilized analytical tools to determine the purity of our products but also identified and evaluated the unintentional contaminants. The scope and expectations for safety continued to grow, leading to the formation of the Product Safety and Regulatory Services (now PS&RA) organization in 1971. The PS&RA organization was born with the mission to deliver sound and data-based decisions about the product safety.

Our toxicologists are among the leaders in the industry. They work at the leading edge of toxicology and human health risk assessment, and routinely publish their findings in the peer-reviewed scientific literature. Since 1960, we have published more than 2,000 articles and book chapters. The two scientists listed below are examples of the high level of scientific achievement attained by our people.

We are a diverse global organization Our human safety experts cover the globe. We have centers of expertise in North America, Europe, Japan, China, and Latin America, which enables us to have in-depth understanding on global regulations and product safety requirements, as well as new developments in risk assessment and safety testing methodologies. It also allows us to build close cooperation and connection with many authoritative safety institutes and regulatory policy makers. P&G provides the world’s consumers a broad spectrum of products ranging from food, cosmetics, and household consumer products to drugs, biocides and powered devices. In every one of these categories we have toxicologists and safety professionals working to ensure our products are safe.

Human safety expertise and research capability PS&RA has more than 500 scientists dedicated to ensuring our products are safe and in compliance with global regulations. They include toxicologists, chemists, and biologists. Our capabilities span a broad range of safety topics including skin, eye, inhalation, and reproductive toxicology, skin and respiratory allergies, genotoxicity/carcinogenicity, risk assessment, and computational modeling and simulation. The experts provides day-to-day product safety support, and collaborate externally to bring the most up to date risk assessment and safety testing methodologies into the company. In addition, we have in-house research capabilities include the following areas. Reproductive toxicity evaluation Assessment of skin irritation and sensitization Biostatistics / Epidemiology Genotoxicity assays Genomic assays applied in various fields of toxicology Research to develop in vitro alternative methods Clinical research Mechanistic research

3 The Tradition & Science of Safe Products

Frank Gerberick

George Daston

Dr. Gerberick has been employed at P&G since 1986, after his postdoctoral fellowship at The Johns Hopkins School of Medicine in the field of pulmonary immunology. Dr. Gerberick has focused his career working in the field of skin toxicology. His laboratory’s research is focused primarily on elucidating the chemical, cellular and molecular mechanisms underlying skin allergy. Currently, he is applying genomic technology to aid the discovery of novel genes involved in skin sensitization as well as developing an in vitro peptide reactivity assay for screening skin allergens. He has over 130 publications and has co-authored a book entitled Toxicology of Contact Dermatitis. He is past-president of SOT’s Dermal Toxicology Specialty Section and is on the Advisory Board of Dermatitis. Dr. Gerberick is the recipient of the SmithKline Beecham Laboratory Animal Welfare Prize and the Society of Toxicology’s Animal Welfare Award.

Dr. Daston received his Ph.D. from the University of Miami and joined P&G in 1985. His current research efforts are in the areas of toxicogenomics and mechanistic toxicology, particularly in addressing how findings in these fields can improve risk assessment of chemicals. Dr. Daston has served as President of the Teratology Society, Councilor of the Society of Toxicology, on the EPA Board of Scientific Counselors, National Toxicology Program Board of Scientific Counselors, National Research Council’s Board of Environmental Studies and Toxicology, and National Children’s Study Advisory Committee. He is Editor of Birth Defects Research: Developmental and Reproductive Toxicology. Dr. Daston has been awarded the Josef Warkany Lectureship by the Teratology Society, the George H. Scott Award by the Toxicology Forum, and was elected a Fellow of AAAS.

The Tradition & Science of Safe Products

4

Risk Characterization

Safety is built into our products right from the start

Hazard Identification Excessive use pattern

Hazard is the inherent property of a substance or object with a potential to cause an adverse or harmful effect on human health.

Lab evaluations

Exploration

Large scale Consumer Research

Market Research

Experimentation

Broadscale Market entry

Production

Post marketing surveillance

Idea

Small scale Consumer Research

Info/ Data

Exposure

Risk

Final Clearance

In-Market In-Market Monitoring

Safety is an integral element of our product development We evaluate every change for every product, everywhere in the world. This is a continuous process as new information is generated and evaluated even after the product is on the market

Application of state-of-the-art product safety principle and approaches Safety assessment is an interdisciplinary approach that focuses on the scientific understanding and measurement of potential ingredient hazards as well as potential ingredient exposures, and ultimately the risks associated with them. P&G follows the National Academy of Sciences (NAS) four-step risk assessment paradigm in safety assessment (National Research Council, National Academy Press, 1983). Hazard Identification Dose Response Assessment

Based on all available relevant information, our human safety expert will identify data gaps and design a testing program if needed.

Exposure

Science Based Safety Evaluation and Regulatory Compliance Hazard

Physical/chemical characterization (including known or suspected impurities) How substance is manufactured and used Target population/sub-populations Existing toxicological, clinical and epidemiological data on substance or related compounds and formulations (e.g. robust ingredient reviews (CIR, SCCP, HPV/SIDS), skin safety data, literature etc.)

Exposure Risk Characterization

Exposure refers to a quantitative measure of the magnitude, duration and frequency of exposure to a potential hazard. Exposure to a potential hazard must be of sufficient magnitude, duration and frequency (i.e. dose) in order for harm to occur. In the words of the fifteenth century ‘father of toxicology’ Paracelsus, “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.” If human exposure is possible, we will define exposure by following considerations to set up the exposure model. Different target groups Route of exposure, define product use scenarios Duration and frequency (Habits & Practices) Multiple product exposure “Worst-case” vs. realistic exposure estimates Evaluations of how much is absorbed vs how much is applied. Our human safety expert will leverage different sources of “Habits and Practices” data, such as the Personal Care Product Council studies for cosmetic use in US, the SCCP guidelines for cosmetics in Europe, or EPA or EU DPD Technical guidance document exposure handbooks for some household products. We also conduct studies to understand consumer use “Habits and Practices” in relevant regions/populations, such as Asian population.

Percutaneous absorption Interferences within product

In P&G, we assemble all relevant available information about the substance or formulation to identify the hazard. The information includes the following aspects.

Product Development

Duration of contact

Frequency of use

Quantity applied

Exposure Assessment

Concentration in product

Body surface location

Risk is the probability that a person will experience an adverse effect from exposure to a chemical or agent. This involves integrating hazard and exposure information because both the hazard and exposure are needed for there to be an assessment of risk. The exposure based risk assessment (EBRA) generally follows a four-step process: Calculate human exposure to ingredient of interest Determine appropriate No Observed Adverse Effect Level (NOAEL) using a weight of evidence approach considering all available data. Compare NOAEL/Exposure to determine Margin of Exposure (MOE) Determine if MOE is sufficiently large to support consumer test or market given uncertainties of the safety data used for the chemical of interest

Route of exposure Rinse - off leave - on Type of product

Type and size of exposed population

Stage of development

Elements important to the exposure assessment process Many of these elements are developed through careful study of consumer habits and practices as well as analytical evaluations in consumer use simulation studies.

Dose-Response Assessment This step characterizes the relationship between dose or concentration of substance and incidence or severity of the response(s). This dose-effect relationship is used to establish the basis for predicting effects at various levels of exposure. Normally, we will consider Safe level (e.g. NOAEL) Threshold levels Shape of dose-response curve Reversibility of effects

Finished Product Evaluation at P&G Every change in every product is evaluated for safety. Finished product evaluations are conducted according to the following principles: The safety profile of the finished product will be determined based on safety data and assessment from individual ingredient and comparison to historical formulations. When necessarily, we will undertake clinical evaluation to confirm the safety of the finished products (e.g. skin compatibility studies and/ or in vitro eye irritation testing).

Post-Market Safety Surveillance Post-marketing safety surveillance represents an important tool in the overall effort to detect and manage emerging safety issues for our products. At P&G, we have formed a dedicated surveillance function. The surveillance experts follow a standardized processes to collect, process, and analyze large volumes of consumer surveillance information to detect potential product safety issues that may emerge after a product is in the market. Data from external information systems (e.g. NHANES, Ingenex) are also used to help the assessment. This is a continuous process and an essential component of our risk assessment process. At P&G, we follow the same principles for management of all post-marketing safety surveillance data: Obtain the most complete and accurate information from the reporting source as possible Comply with all applicable regulatory requirements related to reporting the adverse event Assess the reported events for possible additional safety or quality evaluation Address the needs of the involved party as completely as possible Conduct regular aggregate analyses of collected data to identify any potential product safety or quality signals that need further evaluation

The risk assessment process which we use to evaluate products A final step, not shown in the diagram above, is risk management in which appropriate application of packaging, labeling, and other measures further reduces risk

5

The Tradition & Science of Safe Products

The Tradition & Science of Safe Products

8

Threshold of Toxicological Concern (TTC)

New trends in safety assessment science Animal Alternatives We have made significant progress in our research to develop alternative methods that will eliminate or greatly reduce the need to test with animals. We have developed, or helped develop, more than 50 alternatives that we use today, including two methods which have been accepted as OECD guidelines – 3T3 NRU Phototoxicity Assay, and Epidern Skin Corrosivity Test. We now have alternative methods in place to address some of the key endpoints for safety testing. Despite this progress, there is more to be done. The remaining endpoints are increasingly complex and developing alternatives to these requires a fundamental understanding of the biology involved with a response and development of tools to monitor those key events that are predictive. The figure below depicts our strategy for developing approaches to alternatives testing. We base our approach on developing a thorough understanding of the biology of the effect then developing assays to predict key events leading to a toxic response. With each step in this strategy we move towards our ultimate goal of replacing animal-based tests with alternatives.

Replacement Available In Development Theoretical Approaches Under Evaluation Mechanistic Research

High

Interim solution

Uncertainty

Low

Reduction, Refinement

The Threshold of Toxicological Concern (TTC) is a risk assessment approach, for establishing acceptable human exposure levels for chemicals with limited toxicity data. It was first developed by the FDA as an approach to assessing food packaging materials, which have the potential to migrate into food at very low levels and has since been expanded for use in a variety of other ways including the assessment of ingredients and contaminants in consumer products .

TTC is based on: Reliance on existing data on various chemical classes of substances to predict the toxicological potential of substances of undetermined toxicity. Acceptance of the concept that the chemical structure defines the potential for toxicity and those structural features can be used to group substances into potency categories. Worse-case assumptions about the threshold of effects possible by a chemical class.

Structure Activity Relationships (SAR) Another tool to help establish a safety profile with limited information is the Structure Activity Relationship. SAR relates the structure of a chemical with either a physicochemical property, environmental fate attribute, and/or specific effect on human health or an environmental species. These correlations may be qualitative (simple SAR) or quantitative (QSAR). Qualitative predictions are based on a comparison of valid measured data from one or more analogs (i.e., structurally similar compounds) with the chemical of interest. For example, terms such as ”similarly toxic”, “less toxic”, or “more toxic” would be used in a qualitative SAR assessment for toxicity. Quantitative predictions, on the other hand, are usually in the form of a regression equation and would thus predict dose-response data as part of a QSAR assessment. P&G human safety experts have applied the QSAR assessment in our daily risk-assessment work. We have been working with leading toxicologists worldwide on SAR model development and applications. We also leveraged many advanced SAR databases and computer software tools such as GRASP, DEREK, METEOR, DiscoveryGateTM and MetabolismTM .

Strategies to eliminate research with animals As our understanding of the fundamental biology and mechanisms of response to chemicals increases we are able to propose ways to monitor key events which may be predictive. As our understanding of these events improves, we move to proposing, then developing, specific assays that can be used to replace tests in animals. In the meantime, we apply reduction and refinement methods to improve existing animal-based assays.

9 The Tradition & Science of Safe Products

The Tradition & Science of Safe Products

10

Collaboration on human safety assessment between P&G and external scientific organization and regulators The P&G researchers work closely with scientists at universities, governmental bodies and industry organizations to share knowledge and work collaboratively on new and improved methods and approaches to advance the science of toxicology. We work with more than 40 different organizations worldwide.

Representative Collaborations American Chemistry Council (ACC), US Center for Animal Alternatives (CAAT), US European Center for Validation of Alternative Methods (ECVAM), Italy European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC), Belgium European Chemical Industry Association (CEFIC), Belgium European Cosmetics Association (COLIPA), Belgium European Chemical Industry Council (CEFIC), Brussels, Belgium European Risk assessment and management (ERASM), Belgium Food and Drug Administration (FDA), US Hamner Institute, Research Triangle Park, North Carolina, USA Health and Environmental Science Institute (HESI), US International Association for Soaps, Detergents, and Maintenance Products (AISE), Belgium International Association of Nonwovens and related industries (EDANA), Belgium International Fragrance Association (IFRA), Belgium Institute for In Vitro Science (IIVS), USA Interagency Coordinating Committee for the Validation of Alternative Test Methods (ICCVAM), US Japanese Cosmetic Industry Association (JCIA), Japan Japanese Soap and Detergent Association (JSDA), Japan Japanese Center for Validation of Alternative Methods (JaCVAM) National Academy of Sciences (NAS), US National Institutes of Environmental Health Sciences (NIEHS), US National Toxicology Program (NTP), US Organization for Economic Cooperation and Development (OECD), France Personal Care Products Council (PCPC), US Research Institute for Fragrance Materials (RIFM), Washington, DC Soap and Detergent Association (SDA), US Society for Risk Analysis (SRA), US Society of Toxicology (SOT), US Toxicology Forum, US Universities Worldwide e.g. Manchester University, Manchester, UK, University Louis Pasteur, Strasbourg, France, University of Cincinnati, Cincinnati, OH, and others. United States Environmental Protection Agency (EPA), US

11

The Tradition & Science of Safe Products

How to learn more about the Safety at P&G One key element of P&G safety program is external communications - sharing scientifically sound, relevant, and meaningful information with key stakeholders and seeking input from outside the company. Where relevant and appropriate, we share information about the ingredients we use, key aspects of our safety evaluations, and various environmental characteristics of products. You could simply go to the below website to get more information on P&G science and safety information.

Laundry and Cleaning Products www.scienceinthebox.com

Beauty Care Products www.pgbeautyscience.com

The Tradition & Science of Safe Products

12

The Tradition & Science of Safe Products