There is no question that multistate foodborne illness outbreaks associated with the microbiological contamination of food products captured the majority of food safety-related headlines in 2006 and 2007. The broad range of affected food categories—from fresh spinach and tomatoes, to further processed foods like peanut butter, canned green beans and ready-to-eat meats—and the resulting spate of product recalls is clearly spurring industry and regulators to speed the development and application of risk-based food protection strategies and initiatives.

While microbiological food safety issues are top-of-mind for many food companies, regulators and consumers, the challenge of assessing the risk posed by emerging environmental chemical contaminants in the food supply is steadily gaining ground in the media spotlight. In addition to last year’s highly publicized contamination of pet food and other products by the chemical adulterant melamine, media reports are more frequently covering potential food safety risk data associated with heavy metals, pesticides, veterinary drug residues, naturally occurring environmental toxins and industrial chemicals. Recent newsmakers, such as methylmercury in fish, acrylamide in fried foods, benzene in soft drinks and dioxins in a variety of foods, are just a few of the chemical food safety issues flowing to the front pages on the wave of new studies and toxicological surveys.

Emerging chemical contaminants are associated with numerous wide-ranging and overlapping environmental issues. Food safety stakeholders face a complex matrix of challenges in identifying, characterizing, preventing and managing risks associated with emerging chemicals effectively. For the food industry, these contaminants or potential contaminants affect every aspect of the supply chain, from every single ingredient that is included in a product, used in the manufacture of the product, or used in the manufacture of any ingredient that goes into the product. Nonetheless, as consumers become more vocal in questioning what chemicals or chemical residues are contained in the products they eat, and as regulatory bodies consider changes in rules or standards regarding materials that companies may use in foods or as processing aids in the manufacture of foods, industry’s imperative is to stay proactive in assessing the risk of emerging chemicals.

To some extent, it is impossible to develop a comprehensive list of chemicals that food companies should focus on, given the complexities of environmental, agricultural, food and chemical composition, supply chain and regulatory factors. However, keeping up-to-date on new public health research, occurrence data, regulatory initiatives, and advanced analytical and control methods will enable food companies to make more informed decisions about which contaminants pose a threat to their businesses and how to mitigate and manage those risks successfully.

Defining Emerging Chemical Contaminants
Today, governments and process authorities throughout the world are focusing efforts on determining the toxicological implications of human exposure to both known and newly identified chemical contaminants, developing standards for methods and levels of detection, identifying prevention and management strategies for industry, and establishing appropriate regulatory or legislative mandates as necessary. But what are we really talking about? The U.S. Geological Survey (USGS) defines emerging chemical contaminants as “any synthetic or naturally occurring chemical or any microorganism that is not commonly monitored in the environment but has the potential to enter the environment and cause known or suspected adverse ecological and(or) human health effects.”

In defining an emerging chemical as “unregulated, recently discovered and potentially of concern to human health and the environment,” known chemicals that have posed problems historically can also be included in the discussion of emerging chemicals. These chemicals, such as benzene or pesticides, can reemerge after years of dormancy as issues to industry. Although these aren’t new chemicals, they are problems that have existed historically and that are revisited with a current population.

As alluded to in the USGS definition, emerging chemicals become known as potential issues through a variety of ways. First, with advances in analytical detection, industry is able to analyze more chemicals to much lower concentrations, resulting in a seemingly unending array of identified compounds that, since now known, must be addressed. We know that chemical contaminants that pose a risk range from pesticides, veterinary drugs, mycotoxins, banned food dyes, industrial chemicals (e.g., acrylamide, perchlorate, benzene), radionuclides, environmental and heavy metals (e.g., arsenic, cadmium, lead, mercury, methylmercury) and persistent organic pollutants (e.g., polybrominated diphenyl ethers, dioxins, polycyclic aromatic hydrocarbons). The ability to detect and measure more chemicals at extremely low levels in environmental, food or water matrices not only adds to the shopping list of potential threats but adds to the complexities of deciphering whether a chemical measured at parts-per-billion or trillion (ppb/ppt) levels rather than a parts-per-million (ppm) level has, in reality, more of a health implication for consumers.

Another less objective reason that some chemical contaminants become known as potential issues to the business involves how the public perceives the safety or wholesomeness of a product, whether the issue raised has real health implications or not. If a product contains some level of arsenic, it may not matter to the consumer that it is well below a threshold limit or is scientifically shown to be of little significance because the compound has a back history associated with adverse health effects. The reality is that in many cases the public perception of a product drives how a product is designed or redesigned even more than scientific fact or evidence to the contrary. Food companies will need to factor this “real problem vs. phantom issue” consideration into their risk assessment strategies.

Sources of Emerging Chemicals
Today, more work is being done in the US and the EU involving the chemical analysis of human tissues, blood and breast milk. As researchers find chemical residues in these clinical samples, the question becomes, where are they coming from and what is the toxicological significance? In other words, when a compound is tested in a laboratory and it is found that it has high toxicity, persists or is not readily degradable, how does that translate to health implications outside of the lab environment?

In general, the areas currently receiving the greatest emphasis by the food and other industries include agricultural residues; additives/colorants/flavors; impurities; manufacturing processes; source water; and packaging. Many industries are beginning to look at various chemical threats to their sector’s businesses, including heavy metals in dyes or other kinds of plasticizers or hydrocarbons found in source water or packaging materials. Although these chemicals are used in very small quantities because their applications cross myriad manufacturing sectors, they can be detected via biomonitoring at wastewater treatment plants or through product evaluations.

Impurities are another big issue under the emerging chemicals umbrella. These represent a “grey zone” not only in terms of identifying the source of an emerging issue but whether a specific impurity carries with it attendant health implications. This goes to the heart of knowing the composition of a product because although the manufacturer may know what materials were put into the product (i.e., the black-and-white components), the company is not necessarily looking for what else is in the product, hence the problem of the “grey zone.” Additionally, a food product manufacturer doesn’t necessarily know how much of an impurity is in that grey zone, what category or level of impurity it represents, or even whether it has some desirable attributes.

Since many nongovernmental organizations (NGOs) and regulators overseeing the implementation of California’s Prop 65 requirements are targeting “impurities” right now, many companies are taking a closer look to see how much they actually know about materials used in their products or in the processing of their products. Similarly, we are beginning to see a lot of material safety data sheets (MSDSs) given to further processing customers by ingredient and raw materials suppliers that make Prop 65 compliance statements, such as “This product may contain…” followed by a long, broad list of organics, metals, processing chemicals, and so on—statements which may indemnify suppliers, resulting in a secondary scale-up of issues and questions from the ingredient supplier to the processing facility, which now knows that a laundry list of chemicals may be in the final product as well. In turn, this raises a specter about what levels of such impurities are in the product as well as questions about what the consumer might be exposed to by ingesting the product.

Other emerging chemical issues to be considered in a food company’s risk analysis include those associated with water sources and packaging. Whether the processor is using water as a product ingredient or in the manufacturing process, there is a possibility that the water contains some impurity or treatment chemical that is carried into the product in low concentrations. Potential packaging issues related to inks, plasticizers, dyes and other potential contaminants are not necessarily associated with the product itself but are tangential to it, which in turn raises questions about the integrity of the product.

Contaminant Reports from the USGS and CDC
The most recent USGS and CDC chemical contaminant reports provide an overview of some specific chemicals of interest that food companies should be aware of when doing risk analysis:

• USGS Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in US Streams, 2002. This paper, published in the American Chemical Society’s journal, Environmental Science & Technology, focused on analytical methods development, environmental occurrence, source identification, and transport and fate of the following target analytes: Veterinary and human antibiotics (22); prescription drugs (19); steroids and hormones (15); and 39 other wastewater-related compounds (insecticides, plasticizers, fire retardants, etc.), for a total of 95 analytes surveyed.

The USGS detected 82 of the 95 targeted analytes, with as many as 38 analytes detected in a sample. The most frequently detected compounds were steroids, non-prescription drugs, insect repellent, detergent metabolites, disinfectants, dyes and plasticizers. Although the initial focus and expectation of the USGS researchers was to find hormones and antibiotics, surprisingly the biggest incidence of chemicals found fell into the “Other” category where they crossed in the different sectors studied (Figure 1). The attached bar charts show the different classes of chemicals identified, their concentrations on the lower scale and the detection frequency on the upper scale. As shown on the chart, fragrances and flavors were detected at low levels but were placed on the list because these residues were found in many survey sites.

Because the USGS surveyors picked up so many of these “other” chemicals, the agency put chemical suppliers on notice that their chemicals were showing up in the environment. This spurred questions aimed at those industries. For example, dye manufacturers were queried about the composition of their dyes, how they are handled by conventional wastewater treatment, and whether there were implications for long-term low-level releases and associated problems. Food manufacturers who receive supplies from chemical manufacturers are also feeling the pressure to answer similar questions about further processed products.

• CDC National Report on Human Exposure to Environmental Chemicals 2005. The nation’s public health agency reports its biomonitoring results every two years as part of the National Health and Nutritional Examination Survey (NHANE). The number of chemical contaminants with public health implications has risen exponentially since the first report was issued in 2001:

—First report, 2001: 27 chemicals
—Second report, 2003: 116 chemicals
—Third report, 2005: 148 chemicals
—Fourth report, due in 2008: 275 chemicals

The upcoming fourth report on human exposure will reportedly list the following environmental chemicals: metals; phthalates; polycyclic aromatic hydrocarbons (PAHs); phytoestrogens; organochlorine pesticides; organophosphate insecticides; herbicides and fungicides; dioxins, furans, and PCBs; phenols; perfluorinated compounds; and volatile organic compounds (VOCs). The new list is comprised of much broader classes of chemical materials which food manufacturers should be aware are going to be under greater scrutiny sooner rather than later.

The reality is that there are an increasing number of chemicals of potential concern to food companies, and therefore, increasing pressure on all organizations in the food supply and distribution chain to address or make plans to address these contaminants. As analytical methodology advances enable lower and lower detection limits—to nanogram and picogram levels in tissue, food and water samples—and as assessments of human and ecological risks are accelerated, the challenge of determining which of myriad chemicals constitute real hazards becomes more difficult. Additionally, educating and communicating risk to consumers effectively becomes more important: When the consumer hears that there is a chemical in a food product, the subtleties of low levels/low risk often do not compute; rather, the automatic assumption is that the chemical will have adverse health implications for them and their children.

There are numerous chemicals left to evaluate (e.g., current state of the science can analyze for only about 150 of more than 3,000 known pharmaceuticals), many of which have not yet been fingerprinted. When one looks at some of the figures supplied in the CDC and USGS surveys, as well as reports from Europe and Canada, many peaks shown in chromatograms have not been identified as specific compounds. However, agencies in Europe and Canada are leading efforts to clean up the gas chromatography-mass spectrometry (GC-MS) quantification report to figure out what those chemicals are. Based on the existing surveys, the odds are that there will be a greater focus on dyes, additives and impurities from an environmental contaminant-human exposure standpoint.

Since it is inevitable that advanced instrumentation will enable the detection and identification of chemical contaminants at some dose in a given sample, so too will questions be raised that will need to be addressed. Does that mean that multinational food companies are going to have to worry about every single chemical as a potential hazard? No, but food industry players can start prioritizing these potential hazards because the focus is going to be on those that are persistent, bioaccumulative or toxic.

Formulating a Risk Reaction
Emerging chemical contaminants of interest to the food industry generally fall into three groups: familiar chemicals that have spurred new concerns; unfamiliar chemicals of interest; and chemicals flagged by regulatory and public health bodies as potential issues that warrant more research.

New Concerns About Familiar Chemicals. Familiar chemical contaminants such as pesticides and heavy metals thought to have been previously addressed can reemerge as new issues years later when a new application is created. Since it is a pretty good bet that these familiar chemicals will come around again, food companies need to gain a good understanding of these chemicals and what levels of use or applications these might have in their businesses.

Benzene is one example that illustrates new concerns raised by a familiar chemical. Benzene, a known carcinogen with an maximum contaminant level (MCL) of 5 ppb established by the U.S. Environmental Protection Agency (EPA), has widespread industrial uses, and ranks in the top 20 industrial chemicals in production volume. It is present in most consumer products made from refined petroleum constituents, and is used in production of plastics, resins and synthetic fibers, as well as in the manufacture of rubbers, lubricants, dyes, detergents, and drugs.

Why is benzene emerging as a renewed potential issue for consumer product manufacturers, particularly for the beverage industry in light of the U.S. Food and Drug Administration’s (FDA) repeated assertions that benzene levels in the vast majority of beverages surveyed by the agency have been measured at less than 1.5 ppb? One of the biggest reasons is that the previous concerns with this familiar chemical focused on human exposure in the petrochemical industry, since benzene comprises 0.5 to 3.5% of gasoline. However, the reality is that benzene is used in numerous applications, including many petrochemical products other than gasoline, so its inclusion in other products, while not an intended end result, will occur if a further process does not eliminate it through refining. As such, benzene is detected in dyes, resins, packaging materials or solvents because it is carried through to the product as an impurity, a precursor or a side contaminant.

Among the new concerns regarding benzene exposure are recent studies that indicate the chemical may be more toxic than currently designated by regulatory agencies. The focus on benzene exposure has expanded in the last several years to individuals using products that contain trace levels of benzene. In addition, benzene is the fastest growing chemical, after asbestos, driving toxic tort litigation. The new questions surrounding this chemical are: Is it more toxic now for some reason, and is there a bigger exposure dose that may cause health implications to the public?

The reemergence of benzene as a contaminant issue reinforces the need for companies to make a commitment to looking at familiar chemicals to identify those that are most likely to become issues again. Food companies should compare existing regulatory thresholds for each familiar chemical of interest with the available scientific findings about each to determine the protection level between the thresholds and the science. Each of those step-ups adds a whole level of perception of risk to the company, especially in cases where there are no absolutes in terms of numerical data or measurements.

Unfamiliar Chemicals on the Horizon. What about the unfamiliar chemicals—the names of which you’ve never heard until some study or news organization suddenly reports that they are the hottest contaminants going? Where are these coming from, and how can industry be prepared to address a potential risk it doesn’t expect?

The first step is to arm yourself with the latest research data. In the US, the USGS and CDC have been conducting broad-based contaminant research for many years, evaluating soil, water, food, tissue and blood samples. Similar efforts are underway in Canada and Europe. These scientific research efforts are the first way that new chemicals of interest are introduced to industry as potential threat issues to business. Government researchers are collecting a range of environmental and food samples and conducting surveys of the subsequent analyses to determine what chemicals or compounds are being detected (i.e., a GC-MS analysis of a food sample to see what organic materials are present and at what peak levels). From these field analyses, researchers began to see peaks for materials that could not be identified, and in pursuing identification have steadily identified these new chemicals of interest, including perfluorinated materials and brominated materials, which have now come under greater scrutiny by regulatory agencies.

The second way in which industry can become informed about new chemicals of interest is to keep abreast of recent governmental and scientific evaluation lists that contain persistent organic pollutants (POPs) and persistent, bioaccumulative, toxic (PBT) pollutants, such as polybrominated diphenyl ether (PBDE) and perfluorinated compounds (PFOA). These are the chemicals that pose future challenges for industry and they are currently under intense evaluation in Europe and Canada, the latter of which is in the midst of completing its prioritization all of chemicals on the national Domestic Substances List (DSL) based on their physico-chemical characteristics, degradability, bioaccumulation potential and toxicity. POPs are materials that, toxicologically:

• Persist in soil, water and food for a long time
• Do not readily degrade
• Are bioaccumulative and exhibit the potential to be picked up in fatty tissues
• Are toxic, either directly or at some point further down the food chain

It is logical to assume that if such materials are detected, isolated and characterized in controlled laboratory settings, it is likely that, depending on use and application, POPs and PBTs will eventually be detected passing through wastewater treatment systems or in the environment by bioaccumulation up through the food chain.

The Canadian approach to reevaluating the compounds on the DSL focused on prioritizing all chemical compounds based on toxicity, bioaccumulation potential and persistence. First, Canada identified those chemicals of highest risk from an environmental and human health perspective, and is now in the process of conducting risk assessments to determine whether restrictions need to be placed on the use of each of those chemicals. After identifying the most persistent and the most toxic chemicals, the Canadian government shared the initial substance list and rankings with industry, encouraging companies to provide more data about chemicals for which they deem the ranking is incorrect, and promised to reevaluate those. This logical, scientific approach to risk ranking of chemical issues has engendered a very good list that food companies look at and consider in terms of behavior of these materials in the environment.

Emerging regulatory issues. Among the emerging regulatory issues of which the food industry should be aware, the top three are children’s health, endocrine disrupting chemicals (EDCs) and nanotechnology.

Children’s Health: Early-Life Susceptibility Assessments. The implications of children’s sensitivities to chemicals has been the elephant in the room for many years. Early life susceptibility studies have shown changes in sensitivities to chemicals depending on age. Although several industries have attempted to prepare for any potential implications of this, it has yet to hit on a large scale. However, it is suggested that companies continue to watch for developments in this area to see if it will drive any product design or product substitutions.

Endocrine Disrupting Chemicals (EDCs). EPA has targeted 87,000 chemicals to screen and test for EDCs—a number that affects virtually every manufacturing industry. Five years ago, many scientists predicted that detection of EDCs in food and water would force companies to pull thousands of products from the market. However, a high potential for false positives during screening limited the ability to effect future regulations. For now, the issue of EDCs is a sleeping giant. As more becomes known about the sources, routes and health implications of EDCs, there remains the possibility of the development of future regulations. In the meantime, it is recommended that industry work to find alternative chemicals or products where possible as a risk reduction measure.

Nanomaterials. Nanotechnology has generated significant press and discussions about its potential benefits in many consumer product applications but there are still many unknowns in terms of the risks that nanomaterials may pose in the long-term. Nanomaterials are novel materials created by engineering on the atomic level that are <100 nm in size (in comparison to a human hair, which is ~80,000 nm), which possess unique properties based on quantum physics and large surface area. Although nanomaterials are often discussed as though they are a single material, materials on the nanoscale actually comprise or refer to a type of technology that can be used in many applications. As such, the technology will have not only different environmental implications but also different processing and human health implications depending on the applications and what kind of chemicals are used on the nanoscale.

Potential hazards from nanotechnology application involve reactivity (i.e., potential issues with how it behaves both in terms of chemical interactions with other materials or chemicals and how it moves in the environment and/or in people), as well as the potential of the nanoscale to increase the bioavailability of chemical contaminants and their transport and mobility in the environment. Similarly, nanoscale particles can penetrate biological barriers and are able to reach deep airways in the lungs, creating an exposure pathway that might not otherwise exist when a non-nanoscale chemical is used in the same application.

The Impact of REACH
One of the biggest changes associated with international chemical regulations today is the European Union’s REACH (Registration, Evaluation and Authorization of Chemicals) regulation, and how companies will respond to the additional data collection efforts required. The EU REACH policy will require manufacturers, importers or downstream users to register chemical substances and to develop technical dossiers that provide data on each hazard and exposure, with increasing registration requirements linked to increasing tonnage. The European Chemical Agency (ECA) will publish a list of substances classified, for example, as PBT (persistent, bioaccumulative and toxic) and conduct risk assessment and make risk management decisions on these substances. Potential industry issues from REACH include additional regulatory burdens (i.e., R&D, testing costs, registration, cost of reformulation); reduced availability of products since some substances will no longer be supported; and demand for REACH compliant substances that could result in product use restrictions and bans that will affect and change market positions and marketing practices.

This new EU regulation is having huge repercussions across industries throughout the world due to tremendous concerns that REACH will force suppliers to pull products off the market. This is not necessarily borne of fear of the regulation itself but fear of the economic impact of the regulation since its implementation will change what companies can put into their products or use in the manufacturing of their products. For the past five years, industrial chemical companies have had the opportunity to provide additional information and assist with these ongoing assessments.

Now that the registration deadline is looming, these chemical suppliers have finalized their short lists of the chemicals that will remain in their portfolios. As more is known about what products will remain in the market and what products will be eliminated because of REACH, food companies will be better able to determine whether there is a need to reformulate products in the event that some of the ingredients used may no longer be available or not available in the form typically used.

As indicated, the implications of REACH go beyond the industrial chemical sector. They also affect downstream users or any business that is buying materials or ingredients for consumer applications. Food companies, for example, as downstream users of ingredients are, under REACH, responsible for those ingredients that go into finished products. Like the industrial chemical companies, food companies will be driven to prioritize what chemicals they can or cannot live without, and to develop alternatives that are acceptable, both from a product quality and an economic feasibility perspective. And, like a great many other industries struggling with the far-reaching implications of REACH on cross-sector supply chains, the food industry will need to focus on how the regulation will impact their businesses in terms of the additional financial burdens associated with increased verification testing programs.

Ulimately, identifying and ranking the risks posed by emerging chemical contaminants is the food company’s best bet in establishing effective prevention, mitigation and/or control measures that will result in the greatest level of food protection. Maintain-ing a good working knowledge of the latest toxicological studies and regulatory initiatives associated with emerging chemical contaminants in foods and understanding the composition and interaction of foods, food-contact materials and emerging chemicals will enable manufacturers to better assess their risk and devise chemical control plans that make sense for their businesses and their
consumers.

Marie T. BenKinney, M.S., a Senior Managing Scientist with Exponent, Inc., is an ecotoxicologist with more than 25 years of experience specializing in environmental toxicology and assessing the fate, exposure and environmental effects of substances, mixtures and formulated products. She has managed the development of overall environmental strategies for new and existing product evaluations, product stewardship program design, and has assisted in negotiations with state, federal and international regulators. BenKinney can be reached at benkinneym@exponent.com.