An Analysis of the Economic Benefit Provisions of the Food Quality Protection Act

What Are the Current Findings Concerning Arsenic in Foods?

Along with proper hand hygiene, disinfection of contaminated surfaces and medical instruments has been a key method of preventing patient-to-environment-to-patient transmission of infectious agents via the hands of healthcare workers.1-3 However, there is growing concern regarding the increase in antibiotic-resistant pathogens for which environmental and device contamination may play a role in disease transmission, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Clostridium difficile, and multidrugresistant aerobic gram-negative bacilli (eg, Pseudomonas aeruginosa and Acinetobacter).1 Proper use of disinfectants plays an important role in reducing person-to-person transmission of these pathogens. For decades, the medical community in the United States has relied on the federal government’s disinfectant testing and registration program for assurance that registered disinfectants meet their label claims. However, recognized flaws in test methodologies could result in registration of ineffective disinfectants.4 Control measures should be instituted at the federal level to improve the test methodology and reduce the frequency of contaminated or ineffective disinfectants and the threat of serious healthcare-associated infections related to disinfectant use. We have previously reviewed the issues surrounding the selection and registration of high-level disinfectants and chemical sterilants.5 However, there are several unique aspects of testing and registration of low-level and intermediate-level disinfectants (eg, microbicidal testing methods) that warrant separate discussion. This article proposes a scheme for testing and registration of low-level and intermediate-level disinfectants that could be used by the U.S. Environmental Protection Agency (EPA). BACKGROUND Chemicals formulated as disinfectants in the United States are registered and regulated in interstate commerce by the Antimicrobial Division, Office of Pesticides Program, EPA. The authority for this activity was mandated by the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) in 1947. In June 1993, the U.S. Food and Drug Administration (FDA) and the EPA issued a “Memorandum of Understanding” that divided responsibility for review and surveillance of chemical disinfectants between the two agencies. Under the agreement, the FDA regulates disinfectants used on critical or semicritical medical devices and antiseptics and the EPA regulates disinfectants used on noncritical surfaces. In 1996, Congress passed the Food Quality Protection Act (FQPA). The Act amended FIFRA regarding several products regulated by both the EPA and the FDA. One provision of FQPA is that regulation of disinfectants used on critical and semicritical medical devices (the EPA continues to regulate non-medical disinfectants) was removed from the jurisdiction of the EPA and now rests solely with the FDA.1,6 Examples of disinfectants that are registered by the EPA with the intent of providing a public health benefit, therefore requiring efficacy data as a condition of their registration, include disinfectants used in hospitals and other healthcare settings on floors, walls, and medical equipment surfaces and household products claiming to have disinfectant activity. There are three types of disinfectant products that the EPA registers based on submitted efficacy data: limited, general or broad-spectrum, and hospital disinfectants. When a disinfectant is represented in its labeling for use in hospitals, medical clinics, dental offices, or any other medical-related facility, it must show

British chef and food activist Jamie Oliver ignited a firestorm in January 2011 when he mentioned on the Late Show with David Letterman that castoreum, a substance used to augment some strawberry and vanilla flavorings, comes from what he described as “rendered beaver anal gland.”1 The next year, vegans were outraged to learn that Starbucks used cochineal extract, a color additive derived from insect shells, to dye their strawberry Frappuccino® drinks2 (eventually, the company decided to transition to lycopene, a pigment found in tomatoes3). Although substances like castoreum and cochineal extract may be long on the “yuck factor,”4 research has shown them to be perfectly safe for most people; strident opposition arose not from safety issues but from the ingredients’ origins. But these examples demonstrate that the public often lacks significant knowledge about the ingredients in foods and where they come from. This is not a new development; the public relationship to food additives has a long history of trust lost, regained, and in some cases lost again. The Federal Food, Drug, and Cosmetic (FD&C) Act of 19385 was passed shortly after the deaths of 100 people who took an untested new form of a popular drug, which contained what turned out to be a deadly additive.6 The new law was consumer oriented and intended to ensure that people knew what was in the products they bought, and that those products were safe. The law has been amended over the years in attempts to streamline and bring order to the sprawling task of assessing and categorizing the thousands of substances used in foods, drugs, and cosmetics. One result of this streamlining is that under current U.S. law, companies can add certain types of ingredients to foods without premarket approval from the thin-stretched Food and Drug Administration (FDA). In other words, there are substances in the food supply that are unknown to the FDA. In 2010 the Government Accountability Office (GAO) concluded that a “growing number of substances … may effectively be excluded from federal oversight.”7 Is this a problem? The answer depends on whom you ask.

Chapter 31 - Risk Assessment and Risk Management: The Regulatory Process

Effective immunization programs have markedly diminished the incidence of vaccine-preventable diseases. As a result, there now exists in society a lower awareness of the actual risks associated with the diseases themselves and a greater prominence of the potential risks of adverse effects associated with vaccines.Concern regarding public reactions to new vaccine safety issues may place pressure on policymakers and/or health care providers to act quickly in response to new information. However, this concern must be tempered by the necessary caution required to assess the intended and unintended risks and benefits of any action undertaken. The interplay of these potentially competing demands is well illustrated by the recent safety concern involving the use of thimerosal in vaccines.Thimerosal is a mercury-containing compound that has been widely used as an antimicrobial agent in vaccines for over 60 years. Human exposure to mercury may have potentially significant health consequences. By mid-1999, the Food and Drug Administration (FDA) had discovered that children could be exposed to an amount of mercury from vaccines that exceeded 1 of 3 existing federal safety thresholds. After this realization, the organized medical and public health communities in the United States became involved in a series of urgent and intense discussions to determine an appropriate response to the issue. This manuscript describes and analyzes the process that led to the July 7, 1999, joint American Academy of Pediatrics (AAP)/US Public Health Service (PHS) statement on thimerosal,1 with the goal of suggesting improvements for managing similar vaccine safety concerns in the future.We conducted structured interviews with over 15 individuals involved in the discussions and negotiations leading to the joint AAP/PHS statement on thimerosal. The individuals represented both the governmental agencies and nongovernmental organizations involved, including the FDA, the Environmental Protection Agency (EPA), the Centers for Disease Control and Prevention (CDC), the National Vaccine Program Office (NVPO), the AAP, and the American Academy of Family Physicians (AAFP). Interviews were conducted through face-to-face meetings or by telephone between January and April 2001. Table 1 lists the individuals interviewed who allowed their identities to be published.The development and implementation of immunization policy in the United States is a cooperative effort among many entities in the public and private sectors (Table 2).The concern over thimerosal in vaccines originated from a confluence of independent events, 1 informal and 1 formal, within the FDA. In the spring of 1998, some individuals within the FDA's Center for Biologics Evaluation and Research (CBER) began to informally consider the increased number of recommended vaccines and the amount of substances, such as mercury, contained in them to which vaccine recipients were exposed. Available literature to help quantify their concern was limited.The formal identification of thimerosal as a concern arose through the FDA's efforts to comply with the Food and Drug Administration 2Modernization Act.2 As mandated by Congress, Section 413(a) of the Act required the FDA to compile a list of drugs and foods that contain "intentionally introduced" mercury compounds and to provide a quantitative and qualitative analysis of these compounds within 2 years of the Act's enactment.The FDA's previous formal review of thimerosal in biological products had occurred in 1976. The convergence of concerns over mercury in vaccines that occurred within the CBER beginning in April 1998 prompted the agency to reassess the risks of thimerosal.3One of the steps of this risk assessment was to investigate the potential exposure of humans to thimerosal in vaccines. Based on the information submitted by industry and FDA internal data, the CBER determined that thimerosal was present in over 30 licensed vaccines in the United States.4,5 The amount of mercury by weight present in each of these vaccines was calculated. The CBER then referred to the recommended childhood immunization schedule to determine the amount of mercury to which young children may be exposed. Of the vaccines that a child could receive in the first 2 years of life, those that contained thimerosal were the 2 available formulations of the hepatitis B vaccine and some formulations of the diphtheria-tetanus-acellular pertussis and Haemophilus influenzae type b vaccines. Looking at cumulative exposure over the first 6 months of life, an infant 6 months old who received all recommended vaccine doses on schedule could be exposed to up to 187.5 μg of mercury.Another step in the risk assessment process was to determine whether thimerosal actually constituted a true health risk; that is, whether there were data demonstrating that this amount of mercury could be potentially harmful to children. To identify whether there were any known health risks from exposure to thimerosal, the CBER conducted a literature review and queried the Vaccine Adverse Event Reporting System, a national surveillance system for voluntarily reported adverse events associated with vaccines. The CBER found that at low doses, thimerosal has been associated with rare hypersensitivity reactions, such as persistent skin sensitization at the site of vaccination. At very high doses (ie, 1000 times higher than levels found in vaccines), thimerosal has been reported to cause neurologic and renal toxicity.An early assessment of the health risks of all forms of mercury by the World Health Organization (WHO) found that insufficient information was available to perform risk calculations for human exposure to ethyl mercury compounds, the type of mercury contained in thimerosal.6 However, the WHO did note that the limited data available suggested that ethyl mercury was probably less hazardous than methyl mercury, because it is metabolized faster in the body.The WHO and 3 US governmental agencies—the FDA, the EPA, and the Agency for Toxic Substances and Disease Registry (ATSDR)—had developed independent guidelines for safe exposure to methyl mercury (Table 3).7–10 Because no guidelines exist for ethyl mercury exposure, the FDA used the guidelines for safe exposure to methyl mercury as a guide for determining whether the mercury (ethyl) dose from thimerosal in vaccines approached a level of concern or health risk.The existence of 3 differing US federal guidelines for methyl mercury was a source of confusion and contention in determining the appropriate response to concern regarding thimerosal in vaccines. Each agency developed their guidelines for different purposes. The most conservative of these guidelines was the level established by the EPA to serve as a warning of mercury in the environment to trigger additional investigation. The ATSDR guideline is set below levels that might cause an adverse health impact in those most sensitive to a particular substance. The FDA guidelines were developed as safe limits for long-term consumption of food contaminated with mercury, particularly fish, which is the main exposure route of humans to methyl mercury. No guidelines were available to assess the risk of exposure in bolus doses by intramuscular injection.Nevertheless, the existing methyl mercury guidelines were the best information available at the time for assessing risk from ethyl mercury exposure. The CBER calculated exposure limits for each of these guidelines based on the average weight at various percentiles in female infants between birth and 26 weeks of age (Table 4). Based on these calculations, the CBER determined that potential exposure to mercury from the recommended childhood vaccines in the first 6 months of life could exceed the EPA methyl mercury guideline, but not the ATSDR, FDA, or WHO guidelines. However, the CBER was unable to determine with certainty whether exposure to thimerosal in vaccines was harmful.In April 1999, results from the preliminary risk assessment were discussed at an internal FDA meeting, and participants realized that there was a clear need for additional data. The CBER began to consult with toxicologists both within the FDA and at the National Center for Environmental Health, and several vaccine researchers, including Neal Halsey, MD, Director of the Institute for Vaccine Safety at Johns Hopkins University. The FDA also initiated discussions with vaccine manufacturers regarding the need to develop thimerosal-free vaccines.3Dr Halsey was invited by the FDA to an internal meeting in mid-June 1999 where he was asked to provide feedback on the results of their preliminary risk assessment regarding thimerosal. On learning of the FDA data, and personally verifying the calculations of the levels of mercury to which children could be exposed, he believed that the issue warranted serious concern and urgent action. At the time, Dr Halsey was soon to complete his term as Chair of the AAP Committee on Infectious Diseases (COID). Dr Halsey previously worked within the CDC's immunization program and had been a member of the Advisory Committee on Immunization Practices (ACIP). As such, he had extensive experience and professional relationships within the US immunization policymaking arena. Beginning around June 24, 1999, Dr Halsey informed many of these contacts of his concern regarding the potential health effects of thimerosal and the results of the FDA's preliminary risk assessment. After notifying the Director of the CDC's National Immunization Program, Dr Halsey met with CDC personnel at the National Immunization Conference on June 25. He also informed several other individuals, including the incoming Chair of the COID, the Chair of the ACIP, and a member of the AAP Board of Directors. In addition to his concern regarding the potential health effects of mercury exposure in infants, Dr Halsey expressed the need for urgent action on the issue because the FDA was planning to send a letter to vaccine manufacturers in the beginning of July 1999 regarding the need to remove thimerosal from vaccines, at which point the information about thimerosal would become public. He believed that publicity surrounding this issue, without action on the part of the PHS and/or the AAP, could result in long-term damage to public confidence in the national immunization system.After Dr Halsey informed these initial contacts of his concerns regarding thimerosal, conversations began to occur among the parties. The Interagency Vaccine Group (IAG) held a conference call on June 28 and reviewed the information from the FDA's preliminary risk assessment. After this call, the IAG formed a special workgroup to address the thimerosal issue. CDC immunization officials also conferred with the AAP, vaccine companies, and internal CDC toxicologists.Significant differences of opinion surfaced regarding the accuracy of the exposure and risk-assessment information concerning thimerosal, its importance, and the need for any immediate discussion or action.To quickly bring representatives of several organizations involved in immunization policymaking together to discuss the issue, a meeting was organized by Dr Halsey and Dr Cooper for June 30, 1999, at the AAP offices in Washington, DC. The selection of the venue for this meeting was deliberate. The initial course of action for the government normally would have been for the ACIP and the National Vaccine Advisory Committee (NVAC) to meet to discuss the issue. However, governmental advisory boards are required by the Federal Advisory Committee Act to provide adequate public notice of meetings and publish meeting agendas in the Federal Register. Given how quickly some individuals believed a meeting should occur, it was not possible to officially convene these advisory bodies in such a short time frame. By having an informal meeting at the offices of the AAP, a frank discussion of the scientific and biological veracity of all available information could take place without delay. As a result, however, this meeting precluded the formal involvement of the ACIP and the NVAC.Drs Cooper and Halsey developed a list of invitees, which included representatives of the CDC, FDA, EPA, AAP, vaccine manufacturers, and toxicologic consultants. An initial goal of the meeting was to achieve consensus on a course of action, as many believed that public presentation of differing views would likely confuse practitioners and parents, and potentially undermine confidence in the national immunization system.At the meeting, FDA representatives shared the results of their preliminary risk assessment, outlining what was known and unknown about the issue and describing the difficulties in determining whether the level of mercury in vaccines should be of concern. Because of the complexities in interpreting the data regarding the potential risk of harm from thimerosal, there was disagreement among the parties present as to its significance. Disagreements existed between organizations, within organizations, and among the toxicologists present at the meeting. Some participants believed strongly that the potential threat to health from thimerosal was significant; others believed that there was no clear evidence that thimerosal was harmful, particularly when compared with the clear health risks of delaying childhood vaccines. The 2 AAP committees represented at the meeting, the COID and the Committee on Environmental Health, were in sharp disagreement on this point. There was also a varied sense of exigency, with some participants believing that urgent action was required, whereas others thought the process should slow down to include other parties in the discussion and address perceived significant gaps in the scientific data. Actions proposed by participants at the meeting ranged from immediately stopping administration of all vaccines containing thimerosal to children under 6 months of age to encouraging vaccine manufacturers to expedite the elimination of thimerosal from vaccines.An overriding concern expressed by all parties at the meeting was the need to maintain the public's trust in the US immunization system by striking the appropriate balance between acknowledgment of the potential risk of harm from thimerosal and the actual risk of harm from not immunizing against vaccine-preventable diseases.It became clear during the June 30, 1999 meeting that no consensus would be reached that day regarding an appropriate course of action. Sharp disagreements regarding the clinical significance of thimerosal exposure were not resolved. Specific individuals who felt most strongly regarding the potential health risk of thimerosal exposure stated that they would independently make public statements if their respective organizations did not support their contentions. The meeting concluded with all participants agreeing that no statement would be released by any individual or organization until after the July 4th weekend, and that discussions between the PHS and the AAP would continue in an attempt to achieve a unified public statement. Leadership in both the AAP and the PHS believed that releasing a joint public statement was crucial for preserving the public's trust in the immunization system.PHS officials in the CDC and elsewhere believed that vaccine manufacturers should be encouraged to expedite the elimination of thimerosal from vaccines, but did not want to make any changes to the childhood immunization schedule. However, CDC officials also felt strongly that it would be in the best interests of the national immunization system and the public's trust for a statement to be developed jointly with the AAP. This prompted David Satcher, MD, PhD, the US Surgeon General and Assistant Secretary for Health, to be involved in the negotiations.After the June 30 meeting, there was significant debate within the AAP as to the appropriate course of action to be taken. Over the next several days, there was constant reconsideration and revision of positions taken among both individuals and committees.On review of available information and opinions, the AAP Board of Directors decided to put forth the position in their negotiations with the PHS that the birth dose of the hepatitis B vaccine be temporarily delayed. They considered the risk of disease to be low except for infants of HBsAg-positive mothers. The Board of Directors believed that hospitals should already have procedures in place to determine the hepatitis B status of mothers and treat the infants of HBsAg-positive status mothers appropriately.Other parties were informally involved in the discussions leading to the joint statement. The AAFP did not think the issue warranted such urgency and believed that the health effects data for methyl mercury on which the EPA guidelines were based were questionable.Many conference calls, meetings, and sharing of draft statements occurred within and between the AAP and the PHS over the course of the July 4, 1999 holiday weekend. The Surgeon General held several discussions with the AAP president to negotiate a compromise position. Although they were extremely concerned about both the short- and long-term consequences of delaying administration of the hepatitis B vaccine, PHS officials agreed to the recommendation to present a unified position to the public.The joint statement was officially released in the late afternoon of July 7, 1999,11 and was published in the MMWR Morbidity and Mortality Weekly Report on July 9, 1999.1First and foremost, it is clear that all parties involved in this process acted in the manner they believed was in the best interest of children in the United States. Even parties that differed most strongly never doubted the intent or purpose of those with whom they disagreed.Only 2 weeks transpired between the time that leaders of the major national organizations involved in US immunization policy learned about the issue of thimerosal in vaccines and the release of the joint AAP/PHS statement. During that time, these individuals and their organizations worked diligently to develop a response that they believed balanced the potential risk from exposure to thimerosal with the actual risk of vaccine-preventable disease and would ensure continued public confidence in the nations' immunization system. Considering the complexity of the information available and the gaps in information relevant to specific concerns, it is not surprising there was significant disagreement regarding the potential risk associated with thimerosal. To some, the process could be considered a success, in that compromise was reached and the "crisis" was addressed. However, others have publicly the that the recommendation to the birth dose of hepatitis B vaccine practitioners and put infants at risk for hepatitis B vaccine as to that the process was a of how not to public health of the IAG would have first learned of the thimerosal issue from FDA who would have informed the of its review of the thimerosal in vaccines. In this however, an individual of the government was the first to many of these soon the FDA should have is a of as is how information should have been other parties. The FDA was to an issue with the IAG when there were many surrounding the potential health risks In the FDA must be sensitive to issues to any under its IAG is to among federal agencies with vaccine issues through meetings and other To the IAG must achieve a balance between that are informed of and agencies to data to other parties the information is released to the public. such to be there must be confidence among the parties that their all from and shared efforts with each the must be as independent and to its of this issue is to ensure that the and of the are not under the or perceived or of any the through the that serious be by the Office of the Secretary for Health and Human to the of the of the including the of and the of meeting that occurred at the AAP offices in Washington, on June 30, 1999, was a in the discussions leading to the joint statement. the of this type of meeting and the in which it was organized was for the AAP, the of action was of the of the Board of are as to the of who or was concern expressed from many was the of vaccine industry representatives at the meeting. The meeting occurred the time of the vaccine safety in Congress, and in a environment in which of between industry and immunization policymakers had been Some participants at the meeting believed that having industry representatives at a meeting could have this may also have the of some meeting the of the vaccine industry to a immunization system be Vaccine manufacturers a of vaccine development and and their in different of immunization policy is concern is that some parties did not in this meeting such as the AAFP or representatives of hospitals that would be by the in the hepatitis B the of the 2 federal immunization advisory the ACIP and the did not in the initial thimerosal because of the perceived of the Federal Advisory Committee Act on meetings on very short The CDC and the have reviewed the and have found that exist for meetings on an to the birth dose of hepatitis B vaccine was not taken by any to the the risk of thimerosal exposure with the known risk of of hepatitis B disease was for However, in some leading to the joint AAP/PHS of the potential impact of delaying the birth dose of the hepatitis B vaccine did not receive some in of stopping the birth dose of hepatitis B vaccine, there was acknowledgment of the potentially significant of the of hospitals the the for this policy to these or the of procedures for determining the hepatitis B status of mothers. There to be effort to the existing literature on the impact of changes in immunization and the times for the of there was an confidence by some in the of hospitals to all mothers for hepatitis B status previous had of such of the impact of the joint statement on infant hepatitis B are now beginning to be have that some hospitals all with hepatitis B vaccine, including those to HBsAg-positive possible is the of information or of the recommendation by hospitals and Because of the of appropriate for and the hepatitis B status of this in policy has led to the of at 1 infant from hepatitis have also that many hospitals have not to doses of the hepatitis B vaccine the of thimerosal-free The of the first dose of hepatitis B vaccine at birth is illustrated by a recent that that children who received the first dose at birth were likely to complete the hepatitis B times of regarding immunization that all parties involved to the short- and long-term intended and unintended consequences of their proposed This type of analysis could take the of the and structured risk assessment process used by other government such as the of the major issues concern and urgency among all parties was the manner in which the would the issue. over the accuracy of in and for vaccine issues in is well However, an overriding issue is the of how should concern over the time of for public or individual health with policymaking must balance concern over the risk of public regarding safety issues with concern over the to ensure that information be to the public.The FDA the safety and of products they are for use and the process of a constant of products available to However, the of thimerosal an to FDA In the when thimerosal was for use in this there were limited available to assess for the of there is no for the FDA to vaccine with is in to some other federal such as the In was that be by the EPA years. Because no such process has been for the FDA, thimerosal not In for a containing mercury, the of most concern is on system At this time, the FDA has no for of the products it the FDA not have a to identify the cumulative amount of thimerosal, which children would receive over the course of the recommended immunization schedule. Each vaccine was for use as an independent agent and the amount of thimerosal contained in each individual vaccine no concern. was when the cumulative amount from all the vaccines contained in the recommended immunization schedule was calculated that concern that should consider to the FDA the to perform of vaccine In that the FDA its and the FDA develop a for of the cumulative amount of to which individuals may be exposed as a result of specific federal of the issues to all parties involved was the existence of differing federal for exposure to mercury from the EPA, the FDA, and the Although each agency had a different purpose in a specific safety the that there was no clear federal consensus on this issue was This allowed different parties to the discussion to over to support their federal agencies that have differing safety for exposure to specific to develop a federal consensus on safe exposure levels determine under which the different guidelines are to be than 1 federal is each agency should be with the for determining a different safety AAP is an organization for its to the of the health and of children. the internal debate that place within the AAP on this issue involved disagreement on the course of action that would be of to the children of the United AAP Board of Directors to its committees for and information regarding specific issues on which it must set However, the exists that the course of within the was in some than the Board of Directors on this issue from specific individuals were to the they may have represented the of the AAP is very that all be to maintain use of this in times of This help ensure that the consensus of than specific individuals, are to help guide the AAP Board of Directors regarding policy have on a of immunization The of these has been and At point efforts have been to information of those involved in immunization policy and in the or review of from the Institute of are now to in such committees for of and having their publicly and public if have the potential to cause significant and professional involvement of leading in the on childhood vaccines were to soon after the June 30, 1999, meeting at the AAP As such, concern over the manner in which any action or might be perceived in this type of environment a of concern and over many this was perceived as a course of action under by a process not in the best interests of the immunization system or children. This also to the development of a and the to act in interviewed but not of the parties involved in this As such, have an and assessment of the events that place in late June and early July However, there exists the that some information may not have been In these interviews were conducted 2 years after this process there may be some of the information process that in the in immunization as a result of concern to thimerosal was and Although there are significant differences of opinion regarding the of the the immunization system in the United States and was by the Program for and Health,

INTERNATIONAL ENVIRONMENTAL HEALTH: Invasion of the Bedbugs

Vaginal research got a desperately needed boost at the National Institutes of Health (NIH) in 1992. That’s when Penny Hitchcock took over the Sexually Transmitted Diseases Branch at the National Institute of Allergy and Infectious Diseases and Nancy Alexander became chief of the Contraceptive Development Branch in the NIH Center for Population Research—posts previously held by men. “Those two got together and discovered NIH had no programs for vaginal research,” says Richard Cone, a Johns Hopkins biophysics professor. Cone had begun developing vaginal contraceptives that would protect against sexually transmitted infections (STIs) in 1980, and until then, struggled to get funding. Mucous membranes in the vagina and vulva rapidly absorb chemicals without metabolizing them. But until recently scant research existed on how chemicals in feminine hygiene products and personal lubricants may affect women’s health. Hitchcock and Alexander soon initiated research programs on vaginal physiology, immunology, and microbicides, eventually funding Cone’s work. These new programs led to groundbreaking discoveries in animals and humans that certain chemicals—including glycerin (glycerol), a common base for personal lubricants—can damage or irritate vaginal1 and rectal2 epithelial cells, potentially increasing the transmission of STIs such as herpes and human immunodeficiency virus. When it comes to reproductive health, research on contraceptives and STIs continues to garner interest worldwide. But a related area—chemical exposures from feminine hygiene products and personal lubricants—has received much less attention. In the United States alone, women spend well over $2 billion per year on feminine hygiene products,3 including tampons, pads, feminine washes, sprays, powders, and personal wipes. But until recently, scant research existed on how chemicals in these products may affect women’s health. As scattered findings emerge, several scientists and interest groups are calling for more research to fill in the gaps.4,5 A recent report by the nonprofit Women’s Voices for the Earth (WVE) points out that feminine hygiene products may use ingredients that are known or suspected endocrine-disrupting chemicals (EDCs), carcinogens, or allergens. And while nearly all women use tampons and sanitary pads, black and Latina women use douches, wipes, powders, and deodorizers more often than women of other races, putting them at greater risk of potential chemical exposures.4 “It’s a little bit edgy. People have been shocked, saying things like ‘I’ve never really thought about [the vagina] being an important internal link to your body,’” says Alexandra Scranton, director of science and research for WVE. “Although it is well known that the vaginal ecosystem is more sensitive and more absorbent than typical skin, there is surprisingly little research out there on feminine care products.” Surveys conducted in the 1990s–2000s gave a sense not only of how commonly some products are used but also how widely use can vary across racial/ethnic groups.

The US Food and Drug Administration (FDA) is a remarkable hybrid. Part regulatory agency, part public health agency, it sits at the intersection of science, law, and public policy. The FDA’s mission can be considered in the context of 2 broad dimensions: the products it regulates and its core functions. Both fall under the rubric of protecting and promoting the public health. The FDA’s remit is both broad and diverse: altogether, the agency has regulatory responsibility for >20% of the US economy. The products it is charged with overseeing through its various centers1 encompass food and cosmetics (regulated by the Center for Food Safety and Applied Nutrition); food and drugs for animals, including companion animals and animals used for food (regulated by the Center for Veterinary Medicine); and medical devices, drugs, and biologics (regulated by the Centers for Devices and Radiological Health, Drug Evaluation and Research, and Biologics Evaluation and Research, respectively). Tobacco products were added to the FDA’s portfolio by the Tobacco Control Act of 2009, and are overseen by the Center for Tobacco Products. Regardless of the specific product regulated, the FDA’s core mission remains the same: to protect the US population by helping to ensure the fundamental safety of the food Americans consume and the medical products prescribed by their clinicians. At the same time, this primary mission is complemented by a mandate to promote the public health by reviewing research and taking appropriate action on the marketing of regulated products in a timely manner. Not only do people need access to advances in nutrition and medical therapies, but also the American spirit is itself characterized by a strong current of scientific and technological innovation. At first glance, differences in these 2 priorities, protecting the public safety and promoting the public health through encouraging innovation, might …

The Food Quality Protection Act (FQPA) was enacted in August 1996 and required the US Environmental Protection Agency (EPA) to reassess all existing and new crop protection active substances using a new set of health and environmental standards to further protect infants and children. The initial fear that many minor or specialty crop use registrations would be lost without adequate replacements has largely been overcome by an aggressive programme by the International Research Project no. 4 (IR‐4) in partnership with the EPA and the crop protection industry to register new, safer, reduced risk products for specialty crop pest control needs. Since the FQPA, the EPA has approved over 5600 new specialty crop uses resulting from IR‐4 residue programmes. This amounts to about 56% of the over 10 000 clearances received by the IR‐4 programme in its 43 year history and about 50% of all new uses granted by the EPA since FQPA. The positive outcomes from these efforts have been partially negated by the lack of tolerances or Maximum Residue Levels (MRLs) in countries to which US produce is exported. This has forced some US specialty crop growers to continue to use older, less desirable products. IR‐4 has been addressing this challenge by cooperating in the NAFTA (North American Free Trade Agreement) countries with Agriculture and Agri‐Food Canada's Pest Management Centre and Health Canada's Pest Management Regulatory Agency to harmonize MRLs through joint projects and regulatory reviews. IR‐4 has also provided leadership for the International Crop Grouping Consulting Committee to harmonize specialty/minor crop groupings and representative crops for residue studies with the long‐term goal being to globally harmonize MRLs.

The passage of the Food Quality Protection Act (FQPA) in August of 1996 increased the role of risk assessment in the decision-making process of the US Environmental Protection Agency (EPA). Although the law and guidance issued by the EPA provide for more sophisticated risk assessments, the databases for many chemicals may not be robust enough for such data-sensitive analyses. FQPA mandated a major change in how the EPA evaluates the safety of pesticides. This change was immediate, without provision for a phase-in period. Consequently, the EPA is still in the process of learning how to evaluate pesticides under the new paradigm. The EPA's task was further compounded by the lack of scientifically tested methodologies for evaluating aggregate and cumulative risk, as required under the new law. Clearly, the EPA is still in a state of transition between evaluating aggregate and cumulative risks to pesticides and evaluating them one chemical and one exposure route at a time. In all likelihood, the transition period will continue as the discipline of risk assessment develops the mental constructs and computational methodologies to fulfil the requirements of the law. In this interim period, therefore, policies are needed so the regulators and the regulated industry know what is currently acceptable, and how the EPA's thinking is evolving.

In this issue of Environmental Health Perspectives (EHP), Schecter et al. (2011) report levels of polybrominated diphenyl ether (PBDE) flame retardants in butter purchased from retail stores. Although the investigators found prevalent levels of PBDEs in butter, they report that one sample had inordinately high levels of octa-, nona-, and deca-BDE congeners, likely from its highly contaminated wrapping paper.

The Food Quality Protection Act of 1996 (FQPA), enacted on August 3,1996, brought about significant changes in the way in which pesticides are registered by the U.S. Environmental Protection Agency (EPA). If not implemented properly, the new requirements of FQPA could lead to the removal from the market of a number of beneficial pesticide products and cause substantial disruptions for agriculture in the United States. For many of these products, there is no suitable alternative pest control tool or the substitute pesticide may not be as efficacious or it may be more costly. Ultimately, the potential loss of many existing products could place American farmers at a disadvantage with foreign growers in competing nations who will continue to enjoy access to a variety of effective pesticides in use today. EPA must rely upon the principles of sound science and base its decisions on actual data when making these important FQPA decisions.

Early lifestage exposure to certain pesticides has been associated with adverse health effects including neurobehavioral deficits and cancer. Protecting children from the effects of dietary pesticide exposure requires risk assessment methodologies that consider children's unique characteristics, such as less variety in diet and greater consumption of food per unit of body weight compared to adults. The U.S. National Academy of Sciences (NAS) called attention to these issues in publishing their landmark report Pesticides in the Diets of Infants and Children in 1993. Three years later, the U.S. Congress unanimously passed the Food Quality Protection Act (FQPA), requiring the Environmental Protection Agency (EPA) to implement several of the report's recommendations in its risk assessment processes, including using updated food consumption data based on children's dietary patterns, considering both cumulative and aggregate exposure, and incorporating an additional safety factor to better protect health during early lifestages. On the 20th anniversary of the report, we focus on the NAS recommendations which EPA is not legally mandated to incorporate in risk assessments, such as the use of probabilistic exposure distributions and data describing the impact of food preparation on residue levels. We discuss the extent to which EPA has implemented the recommendations that were not required by FQPA and the challenges faced in implementing the remaining recommendations. Finally, looking toward the future of risk assessment for children's dietary exposure to pesticides, we review recent recommendations from internal and external advisors and the peer-reviewed literature. We explore additional areas of focus, such as the use of epidemiological data in quantitative risk determinations and continued support of data collection on children's exposure to pesticides, and discuss remaining opportunities to improve the protection of children worldwide through dietary risk assessment.

Successful Investigational New Drug Preparation without Reinventing the Wheel

The U.S. Food and Drug Administration (FDA) is accountable for the safety and security of human and veterinary drugs, biological products, much of the U.S. food supply, devices that emit radiation, cosmetics, and medical devices. Title III of the Bioterrorism Preparedness and Response Act of 2002 specifically designates the FDA as being responsible for the safety and integrity of the nation's food and drug supply, and recognizes FDA's oversight of 80 per cent of the entire U.S. food supply. The FDA must provide for the security of both finished food products within United States and the facilities involved in domestic and imported food manufacture and processing. Further, on May 30, 2002, the FDA announced a new regulation aiming to expedite approval of drugs and other products developed to reduce or mitigate the effects of biological, chemical, or radiological terrorism agents. The FDA's responsibilities in food security and counterterrorism are reviewed.