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Quaternary ammonium compounds (QACs), a large class of chemicals that includes high production volume substances, have been used for decades as antimicrobials, preservatives, and antistatic agents and for other functions in cleaning, disinfecting, personal care products, and durable consumer goods. QAC use has accelerated in response to the COVID-19 pandemic and the banning of 19 antimicrobials from several personal care products by the US Food and Drug Administration in 2016. Studies conducted before and after the onset of the pandemic indicate increased human exposure to QACs. Environmental releases of these chemicals have also increased. Emerging information on adverse environmental and human health impacts of QACs is motivating a reconsideration of the risks and benefits across the life cycle of their production, use, and disposal. This work presents a critical review of the literature and scientific perspective developed by a multidisciplinary, multi-institutional team of authors from academia, governmental, and nonprofit organizations. The review evaluates currently available information on the ecological and human health profile of QACs and identifies multiple areas of potential concern. Adverse ecological effects include acute and chronic toxicity to susceptible aquatic organisms, with concentrations of some QACs approaching levels of concern. Suspected or known adverse health outcomes include dermal and respiratory effects, developmental and reproductive toxicity, disruption of metabolic function such as lipid homeostasis, and impairment of mitochondrial function. QACs' role in antimicrobial resistance has also been demonstrated. In the US regulatory system, how a QAC is managed depends on how it is used, for example in pesticides or personal care products. This can result in the same QACs receiving different degrees of scrutiny depending on the use and the agency regulating it. Further, the US Environmental Protection Agency's current method of grouping QACs based on structure, first proposed in 1988, is insufficient to address the wide range of QAC chemistries, potential toxicities, and exposure scenarios. Consequently, exposures to common mixtures of QACs and from multiple sources remain largely unassessed. Some restrictions on the use of QACs have been implemented in the US and elsewhere, primarily focused on personal care products. Assessing the risks posed by QACs is hampered by their vast structural diversity and a lack of quantitative data on exposure and toxicity for the majority of these compounds. This review identifies important data gaps and provides research and policy recommendations for preserving the utility of QAC chemistries while also seeking to limit adverse environmental and human health effects.

The exposome is a term used to characterize exposure to all exogenous environmental agents, socioeconomic conditions, lifestyle, and diet along with markers of endogenous processes across the lifetime of an organism or community of interest. It integrates exposures with molecular or apical responses over time. Measures of the exposome enable data-driven discovery or hypothesis-free research, identifying associations between exposures and biologic endpoints of importance. Two strategies for linking the exposome to health outcomes have been described, and both can be useful. A “top-down” approach adopts untargeted analytic including omic methods to measure features of exogenous and endogenous exposures in biologic specimens. This approach allows contrasts of profiles between diseased and healthy populations. Omic profiles can be used to generate hypotheses to identify particularly relevant exposures, develop biomarkers for high-throughput screens, and determine sources of exposure. A “bottom-up” approach starts with a set of exposures from multiple sources to determine pathways or networks by which those exposures lead to disease. This is laborious and if confined to external sources of exposure, it misses chemical features of the internal environment associated with, for example, metabolism, gender, inflammation, obesity, stress, and discrimination. Most kinds of cancer are multifactorial in origin, and a causal pie model is often used to depict this complexity. Various combinations of component causes accumulate over a lifetime before becoming sufficient to initiate tumor formation and growth. Key events, alone and in combination, initiate adverse outcome pathways. Early biologic changes at low dose levels, exposures during critical windows of vulnerability during various life stages, interactions between exposures and components of mixtures, and gene-environment and internal-external interactions must be considered. In addition to technological challenges, this presentation will briefly raise four issues that must be considered when applying the concept of the exposome to the origins and prevention of cancer: 1) Biologic assumptions: Which signatures, biomarkers, key events, or adverse outcome pathways are important in the pathogenesis of cancer and what determines their variability among individuals or communities? 2) What biologic changes associated with measures of the exposome are adaptive or adverse? When do adaptive responses become adverse? 3) Multilevel variables—individual, family, community, and societal—influence disease risk. Which chemical and nonchemical stressors should be included in exposome assessment? 4) For purposes of prevention, what are the various sources of relevant exposures and their relative ranking in aggregated exposure pathways associated with adverse outcome pathways related to cancer? Citation Format: Ted Schettler. The exposome and cancer [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA18.

Summary: The Florence Statement on Triclosan and Triclocarban documents a consensus of more than 200 scientists and medical professionals on the hazards of and lack of demonstrated benefit from common uses of triclosan and triclocarban. These chemicals may be used in thousands of personal care and consumer products as well as in building materials. Based on extensive peer-reviewed research, this statement concludes that triclosan and triclocarban are environmentally persistent endocrine disruptors that bioaccumulate in and are toxic to aquatic and other organisms. Evidence of other hazards to humans and ecosystems from triclosan and triclocarban is presented along with recommendations intended to prevent future harm from triclosan, triclocarban, and antimicrobial substances with similar properties and effects. Because antimicrobials can have unintended adverse health and environmental impacts, they should only be used when they provide an evidence-based health benefit. Greater transparency is needed in product formulations, and before an antimicrobial is incorporated into a product, the long-term health and ecological impacts should be evaluated. https://doi.org/10.1289/EHP1788

© 2016, Public Health Services, US Dept of Health and Human Services. All rights reserved. Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.

Summary: Narrative approaches and storytelling are emerging as powerful health promotion tools that can spark interest, increase understanding of determinants of health, and translate complex science. A Story of Health, a multimedia e-book with continuing education credits was designed to harness the power of storytelling to increase environmental health literacy. Health professionals are a key audience. They recognize that patients may be suffering from preventable illnesses of environmental origin but often feel ill-equipped to educate individuals and families about risks associated with common exposures. A Story of Health seeks to fill this gap and help readers develop the competencies they need in order to help patients make informed choices, reduce health risks, improve quality of life, and protect the environment. Americans rate nurses and medical doctors as having the highest honesty and ethical standards of all professions. These medical professionals can play a key role in changing patterns of patient behavior and influencing public policies. The e-book provides an easily accessible method of developing environmental health competency. The multimedia format with graphical interpretations allows for quick reviews of topics or for more in-depth analysis via links to additional resources. The CE evaluations have been overwhelmingly positive.

Neurotoxicology is entering a new phase in how it views and practices risk assessment. Perhaps more than any of the other disciplines that comprise the science of toxicology, it has been compelled to consider a daunting array of factors other than those directly coupled to chemical and dose, and the age and sex of the subject population. In epidemiological investigations, researchers are increasingly cognizant of the problems introduced by allegedly controlling for variables classified as confounders or covariates. In essence, they reason, the consequence is blurring or even concealing interactions of exposure with modifiers such as the individual’s social ecology. Other researchers question the traditional practice of relying on values such as NOAELs when they are abstracted from a biological entity that in reality represents a multiplicity of intertwined systems. Although neurotoxicologists have come to recognize the complexities of assessing risk in all its dimensions, they still face the challenge of communicating this view to the health professions at large.

Background Parkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk. Methods In June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD. Results We describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs. Conclusions PD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.

Phthalates are industrial chemical additives used primarily to soften and confer flexibility to plastics. In their pure form, phthalates are clear, oily liquids that are highly lipophilic and poorly soluble in water. They are a key component in a wide range of products, including but not limited to flexible polyvinyl chloride (PVC) plastics, vinyl tile, food packaging, insecticides, pharmaceuticals, and personal care products [Agency for Toxic Substances and Disease Registry (ATSDR) 2001, 2002; National Toxicology Program Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) 2003; Schettler 2006]. Because they are not chemically bound to the plastics, phthalates can be released as the products are used and discarded. The Centers for Disease Control and Prevention (CDC) measured urinary concentrations of phthalate metabolites in representative samples of the noninstitutionalized U.S. population, and for several phthalates, detectable levels of their metabolites were present in more than three-quarters of the participants (CDC 2005). These data confirm that the general population in the United States is exposed to phthalates. Some animal studies suggest that at least some phthalates are developmental and reproductive toxicants (ATSDR 2001, 2002; NTP-CERHR 2000a, 2000b, 2003, 2005), although the effects on human health have not been extensively described, and the effective toxic doses of phthalates in these animal studies are many times higher than typical human exposures. Unusually high levels of exposure may occur, however, among infants admitted to neonatal intensive care units (NICUs), because of their small body mass and the use of phthalate-containing medical devices in their care (Calafat et al. 2004; Green et al. 2005). Of particular relevance is di(2-ethylhexyl) phthalate (DEHP), which is used as a plasticizer in a variety of medical products (U.S. Food and Drug Administration 2002), including those found in the NICU, such as bags containing blood, plasma, intravenous fluids, and total parenteral nutrition; tubing associated with their administration; nasogastric tubes; enteral feeding tubes; umbilical catheters; extracorporeal membrane oxygenation (ECMO) circuit tubing; hemodialysis tubing; respiratory masks and endotracheal tubes; and examination gloves. DEHP migrates out of the plastic into blood or other lipid-containing solutions in contact with the plastic, a phenomenon observed with blood stored in PVC bags (Peck and Albro 1982; Rock et al. 1984) and endotracheal tubes (Latini and Avery 1999). The rate of DEHP leaching depends on the type of solution in contact with the plastic material and on temperatures at the time of use, storage time, and percent DEHP in the plastic product (Marcel 1973). Overall, however, estimates of infants’ exposure to DEHP from common NICU devices exceed typical daily adult exposure [3–30 μg/kg body weight (bw)/day] (NTP-CERHR 2005) by one to two orders of magnitude, approaching the lowest observed adverse effect level (LOAEL) in animal studies (14–23 mg/kg bw/day) (NTP-CERHR 2005). The susceptibility of neonates in the NICU to high DEHP exposures may be compounded by their impaired ability to clear phthalates from their bodies. Until an age of 3 months, infants have immature glucuronidation pathways (Leeder and Kearns 1997). Because glucuronidation, via enzymes such as uridine diphosphate-glucuronosyltransferase, facilitates urinary excretion of phthalates and other xenobiotics, a reduced potential for glucuronidation may lead to slower excretion and higher concentrations of mono(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP, in neonates than in older children and adults. Neonates also have elevated gastric lipase activity (Hamosh 1990), which may enhance their ability to convert DEHP to MEHP. We recently demonstrated that the intensiveness of DEHP-containing product use in NICU neonates is associated with higher exposure to DEHP, as reflected in elevated urinary concentrations of MEHP (Green et al. 2005). Although the median urinary concentration of MEHP among these neonates was five to seven times the median concentrations observed in the noninstitutionalized U.S. population (CDC 2005), 20% of these neonates had MEHP concentrations that were less than or equal to the limit of detection (LOD), 0.87 ng/mL. The absence of detectable levels of MEHP could have been caused by the relative absence of exposure to DEHP among these infants. However, MEHP is a minor urinary metabolite of DEHP. Oxidative metabolites, such as mono(2-ethyl-5-hydroxylhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), are more abundant in urine than is MEHP (Koch et al. 2004a, 2005). Specifically, MEHHP and MEOHP appear in urine at levels at least five times as great as does MEHP (Barr et al. 2003; Becker et al. 2004; CDC 2005; Kato et al. 2004; Koch et al. 2003b, 2004b; Silva et al. 2006) and thus may be more sensitive than MEHP as biomarkers of DEHP exposure. In addition, as phthalate research has expanded, investigations have adopted a panel of several phthalate metabolites emanating from a range of parent phthalates (e.g., Hoppin et al. 2004; Swan et al. 2005). Although the metabolites can be analyzed separately, this approach does not acknowledge their biologic relationships and independencies. For example, exposure to DEHP results in elevations in urinary concentrations of MEHP, MEHHP, and MEOHP, but not monobutyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP). Therefore, in this follow-up report, we studied the intensiveness of the same 54 neonates’ exposure to DEHP-containing medical devices in relation to urinary concentrations of two oxidative metabolites of DEHP. We also evaluated urinary concentrations of monobenzyl phthalate (MBzP), a metabolite of benzylbutyl phthalate (BzBP), and MBP, a metabolite of DBP and a minor metabolite of BzBP (Anderson et al. 2001). Exposures to DBP and BzBP have not been evaluated for neonates in the NICU. Using a structural equation model (SEM), we integrated information from all five biomarkers to estimate the relations among use of DEHP-containing products, infants’ sex, and exposure to DEHP, DBP, and BzBP.

Objective: Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in medical products made with polyvinyl chloride (PVC) plastic and may be toxic to humans. DEHP is lipophilic and binds non-covalently to PVC, allowing it to leach from these products. Medical devices containing DEHP are used extensively in neonatal intensive care units (NICUs). Among neonates in NICUs, we studied exposure to DEHP-containing medical devices in relation to urinary levels of mono(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP. Design: We used a cross-sectional design for this study. Participants: We studied 54 neonates admitted to either of two level III hospital NICUs for at least 3 days between 1 March and 30 April 2003. Measurements: A priori, we classified the infants’ exposures to DEHP based on medical products used: The low-DEHP exposure group included infants receiving primarily bottle and/or gavage feedings; the medium exposure group included infants receiving enteral feedings, intravenous hyperalimentation, and/or nasal continuous positive airway pressure; and the high exposure group included infants receiving umbilical vessel catheterization, endotracheal intubation, intravenous hyperalimentation, and indwelling gavage tube. We measured MEHP in the infants’ urine using automated solid-phase extraction/isotope dilution/high-performance liquid chromatography/ tandem mass spectrometry. Results: Urinary MEHP levels increased monotonically with DEHP exposure. For the low-, medium-, and high-DEHP exposure groups, median (interquartile range) MEHP levels were 4 (18), 28 (58), and 86 ng/mL (150), respectively (p = 0.004). After adjustment for institution and sex, urinary MEHP levels among infants in the high exposure group were 5.1 times those among infants in the low exposure group (p = 0.03). Conclusion: Intensive use of DEHP-containing medical devices in NICU infants results in higher exposure to DEHP as reflected by elevated urinary levels of MEHP.

Developmental, learning, and behavioral disabilities are a significant public health problem. Environmental chemicals can interfere with brain development during critical periods, thereby impacting sensory, motor, and cognitive function. Because regulation in the United States is based on limited testing protocols and essentially requires proof of harm rather than proof of lack of harm, some undefined fraction of these disabilities may reflect adverse impacts of this "vast toxicological experiment" (H. L. Needleman, as quoted in B. Weiss & P. J. Landrigan, 2000, p. 373). Yet the hazards of environmental pollutants are inherently preventable. Psychologists can help prevent developmental disabilities by mobilizing and affecting public policy, educating and informing consumers, contributing to interdisciplinary research efforts, and taking action within their own homes and communities to reduce the toxic threat to children.

The health care industry makes a unique contribution to the potential public health and environmental impacts of sewage sludge production and disposal. As materials flow into and out of health care facilties, potentially hazardous substances, like mercury, solvents, and pharmaceutical compounds, are introduced into the waste stream and ultimately into sewage sludge. Although the hazards posed by these practices are often not fully understood or the risks quantified, concern about impacts on public health and the environment is fully justified. How to deal with the uncertainties surrounding the impacts of these practices becomes an ethical as well as a scientific question. A precautionary approach to materials manufacture, use, and disposal encourages us to look upstream and to re-design products and systems in ways that primarily prevent problems rather than dealing with them at the “end of the pipe.” Early warning systems, shifting the burden of proof, alternatives assessment, and monitoring programs are suggested as interventions that might be used as part of a precautionary approach to addressing the generation and disposal of sewage in an industrial society.

Learning disabilities, attention deficit hyperactivity disorder, developmental delays, and emotional and behavioral problems are among childhood disabilities of increasing concern. Interacting genetic, environmental, and social factors are important determinants of childhood brain development and function. For many reasons, however, studying neurodevelopmental vulnerabilities in children is challenging. Moreover, inadequate incidence and trend data interfere with full understanding of the magnitude of the problem. Despite these difficulties, extensive laboratory and clinical studies of several neurodevelopmental toxicants, including lead, mercury, polychlorinated biphenyls, alcohol, and nicotine, demonstrate the unique vulnerability of the developing brain to environmental agents at exposure levels that have no lasting effect in adults. Historically, understanding the effects of these toxicants on the developing brain has emerged slowly while generations of children are exposed to unsafe levels. Unfortunately, with few exceptions, neurodevelopmental toxicity data are missing for most industrial chemicals in widespread use, even when populationwide exposures are documented. The personal, family, and communitywide costs of developmental disabilities are profound. In addition to the need for more research, a preventive public health response requires mitigation of exposures to potential neurodevelopmental toxicants when available evidence establishes the plausibility of harm, despite residual toxicologic uncertainties.

Background Polyvinyl chloride plastics (PVC), made flexible through the addition of di-2-ethylhexyl phthalate (DEHP), are used in the production of a wide array of medical devices. From the late 1960s, leaching of DEHP from PVC medical devices and ultimate tissue deposition have been documented. Methods A critical review of DEHP exposure, metabolism, and toxicity data from human and animals studies was undertaken. A brief analysis of alternatives to DEHP-plasticized PVC for use in medical device manufacture was completed. Results DEHP leaches in varying concentrations into solutions stored in PVC medical devices. Certain populations, including dialysis patients and hemophiliacs may have long-term exposures to clinically important doses of DEHP, while others, such as neonates and the developing fetus, may have exposures at critical points in development. In vivo and in vitro research links DEHP or its metabolites to a range of adverse effects in the liver, reproductive tract, kidneys, lungs, and heart. Developing animals are particularly susceptible to effects on the reproductive system. Some adverse effects in animal studies occur at levels of exposure experienced by patients in certain clinical settings. DEHP appears to pose a relatively low risk of hepatic cancer in humans. However, given lingering uncertainties about the relevance of the mechanism of action of carcinogenic effects in rodents for humans and interindividual variability, the possibility of DEHP-related carcinogenic responses in humans cannot be ruled out. Conclusions The observed toxicity of DEHP and availability of alternatives to many DEHP-containing PVC medical devices presents a compelling argument for moving assertively, but carefully, to the substitution of other materials for PVC in medical devices. The substitution of other materials for PVC would have an added worker and community health benefit of reducing population exposures to DEHP, reducing the creation of dioxin from PVC production and disposal, and reducing risks from vinyl chloride monomer exposure. Am. J. Ind. Med. 39:100–111, 2001. © 2001 Wiley-Liss, Inc.

Phthalate exposures in the general population and in subpopulations are ubiquitous and widely variable. Many consumer products contain specific members of this family of chemicals, including building materials, household furnishings, clothing, cosmetics, pharmaceuticals, nutritional supplements, medical devices, dentures, children's toys, glow sticks, modelling clay, food packaging, automobiles, lubricants, waxes, cleaning materials and insecticides. Consumer products containing phthalates can result in human exposures through direct contact and use, indirectly through leaching into other products, or general environmental contamination. Historically, the diet has been considered the major source of phthalate exposure in the general population, but all sources, pathways, and their relative contributions to human exposures are not well understood. Medical devices containing di-(2-ethylhexyl) phthalate are a source of significant exposure in a susceptible subpopulation of individuals. Cosmetics, personal care products, pharmaceuticals, nutritional supplements, herbal remedies and insecticides, may result in significant but poorly quantified human exposures to dibutyl phthalate, diethyl phthalate, or dimethyl phthalate. Oven baking of polymer clays may cause short-term, high-level inhalation exposures to higher molecular weight phthalates.

A mitogenic agent in corncob bedding and fresh corn products disrupts sexual behavior and estrous cyclicity in rats. The mitogenic activity resides in an isomeric mixture of linoleic acid derivatives with a tetrahydrofuran ring and two hydroxyl groups (THF-diols) that include 9, (12)-oxy-10,13-dihydroxystearic acid and 10, (13)-oxy-9,12-dihydroxystearic acid. Synthetic THF-diols stimulated breast cancer cell proliferation in vitro and disrupted the estrous cycle in female rats at oral doses of approximately 0.30 mg/kg body weight/day. Exposure to THF-diols may disrupt endocrine function in experimental animals at doses approximately 200 times lower than classical phytoestrogens, promote proliferation of breast or prostate cancer, and adversely affect human health.

Developmental disabilities result from complex interactions of genetic, toxicologic (chemical), and social factors. Among these various causes, toxicologic exposures deserve special scrutiny because they are readily preventable. This article provides an introduction to some of the literature addressing the effects of these toxicologic exposures on the developing brain. This body of research demonstrates cause for serious concern that commonly encountered household and environmental chemicals contribute to developmental disabilities. The developing brain is uniquely susceptible to permanent impairment by exposure to environmental substances during time windows of vulnerability. Lead, mercury, and polychlorinated biphenyls (PCBs) have been extensively studied and found to impair development at levels of exposure currently experienced by significant portions of the general population. High-dose exposures to each of these chemicals cause catastrophic developmental effects. More recent research has revealed toxicity at progressively lower exposures, illustrating a "declining threshold of harm" commonly observed with improved understanding of developmental toxicants. For lead, mercury, and PCBs, recent studies reveal that background-population exposures contribute to a wide variety of problems, including impairments in attention, memory, learning, social behavior, and IQ. Unfortunately, for most chemicals there is little data with which to evaluate potential risks to neurodevelopment. Among the 3000 chemicals produced in highest volume (over 1 million lbs/yr), only 12 have been adequately tested for their effects on the developing brain. This is a matter of concern because the fetus and child are exposed to untold numbers, quantities, and combinations of substances whose safety has not been established. Child development can be better protected by more precautionary regulation of household and environmental chemicals. Meanwhile, health care providers and parents can play an important role in reducing exposures to a wide variety of known and suspected neurodevelopmental toxicants that are widely present in consumer products, food, the home, and wider community.

Environmental scientists play a key role in society's responses to environmental problems, and many of the studies they perform are intended ultimately to affect policy. The precautionary principle, proposed as a new guideline in environmental decision making, has four central components: taking preventive action in the face of uncertainty; shifting the burden of proof to the proponents of an activity; exploring a wide range of alternatives to possibly harmful actions; and increasing public participation in decision making. In this paper we examine the implications of the precautionary principle for environmental scientists, whose work often involves studying highly complex, poorly understood systems, while at the same time facing conflicting pressures from those who seek to balance economic growth and environmental protection. In this complicated and contested terrain, it is useful to examine the methodologies of science and to consider ways that, without compromising integrity and objectivity, research can be more or less helpful to those who would act with precaution. We argue that a shift to more precautionary policies creates opportunities and challenges for scientists to think differently about the ways they conduct studies and communicate results. There is a complicated feedback relation between the discoveries of science and the setting of policy. While maintaining their objectivity and focus on understanding the world, environmental scientists should be aware of the policy uses of their work and of their social responsibility to do science that protects human health and the environment. The precautionary principle highlights this tight, challenging linkage between science and policy.

The precautionary principle has been incorporated as a belief statement in international agreements for more than a decade. The 1998 Wingspread definition of the principle was the first to bring together four components that, in the past two years, have formed the elements of a broader, overarching approach to precaution that is a robust basis for its specific implementation: prompt action even in the face of scientific uncertainty, burden of proof and persuasion on proponents of potentially hazardous technologies, assessment of alternatives, and transparency. This broad approach to precaution is in direct conflict with the simplistic, easily manipulated principles and methods of risk assessment-based risk management being exported by U.S. officialdom. In contrast to risk assessment, precaution, broadly defined, incorporates the full range of human intelligence in the task of protecting human health and the environment: flexibility, foresight, fairness, thoughtful consideration, and honesty.

Although much research focuses on the role of single variables affecting reproductive health, it is essential to remain aware of complex interactions among many variables in the real world. Potential relationships between biologic levels of the essential micronutrient zinc and the response to exposure to teratogens are illustrative.