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In this eye-opening expose, David Michaels reveals how unscrupulous product-defense consultants have increasingly shaped and skewed the scientific literature, manufactured and magnified scientific uncertainty, and influenced policy decisions to the advantage of polluters and the manufacturers of dangerous products. He proves that our regulatory system is broken and offers concrete, workable suggestions for how it can be restored by taking the politics out of science and ensuring that concern for public safety, rather than private profits, guides our regulatory policy.

Beginning with the development of the atomic bomb during World War II, the United States continued to build nuclear weapons throughout the Cold War. Thousands of people mined and milled uranium, conducted research on nuclear warfare, or worked in nuclear munitions factories around the country from the 1940s through the 1980s. Such work continues today, albeit to a smaller extent. The Department of Energy (DOE) is now responsible for overseeing those sites and facilities, many of which were, and continue to be, run by government contractors. The materials used at those sites were varied and ranged from the benign to the toxic and highly radioactive. Workers at DOE facilities often did not know the identity of the materials with which they worked and often were unaware of health risks related to their use. In many instances, the work was considered top secret, and employees were cautioned not to reveal any work-related information to family or others. Workers could be exposed to both radioactive and nonradioactive toxic substances for weeks or even years. Consequently, some of the workers have developed health problems and continue to have concerns about potential health effects of their exposures to occupational hazards during their employment in the nuclear weapons industry. In response to the concerns expressed by workers and their representatives, DOL asked the Institute of Medicine (IOM) to review the SEM database and its use of a particular database, Haz-Map, as the source of its toxic substance-occupational disease links. Accordingly, this IOM consensus report reflects careful consideration of its charge by the committee, and describes the strengths and shortcomings of both. To complete its task, IOM formed an ad hoc committee of experts in occupational medicine, toxicology, epidemiology, industrial hygiene, public health, and biostatistics to conduct an 18-month study to review the scientific rigor of the SEM database. The committee held two public meetings at which it heard from DOL Division of Energy Employee Occupational Illness Compensation (DEEOIC) representatives, the DOL contractor that developed the SEM database, the developer of the Haz-Map database, DOE worker advocacy groups, and several individual workers. The committee also submitted written questions to DOL to seek clarification of specific issues and received written responses from DEEOIC. The committee's report considers both the strengths and weaknesses of the SEM and the Haz-Map databases, recognizing that the latter was developed first and for a different purpose. The committee then discusses its findings and recommends improvements that could be made in both databases with a focus on enhancing the usability of SEM for both DOL claims examiners and for former DOE workers and their representatives. Review of the Department of Labor's Site Exposure Matrix Database summarizes the committee's findings.

Risk assessment has become a dominant public policy tool for making choices, based on limited resources, to protect public health and the environment. It has been instrumental to the mission of the U.S. Environmental Protection Agency (EPA) as well as other federal agencies in evaluating public health concerns, informing regulatory and technological decisions, prioritizing research needs and funding, and in developing approaches for cost-benefit analysis. However, risk assessment is at a crossroads. Despite advances in the field, risk assessment faces a number of significant challenges including lengthy delays in making complex decisions; lack of data leading to significant uncertainty in risk assessments; and many chemicals in the marketplace that have not been evaluated and emerging agents requiring assessment. Science and Decisions makes practical scientific and technical recommendations to address these challenges. This book is a complement to the widely used 1983 National Academies book, Risk Assessment in the Federal Government (also known as the Red Book). The earlier book established a framework for the concepts and conduct of risk assessment that has been adopted by numerous expert committees, regulatory agencies, and public health institutions. The new book embeds these concepts within a broader framework for risk-based decision-making. Together, these are essential references for those working in the regulatory and public health fields.

Advances in the biological sciences have led to an ongoing paradigm shift in toxicity testing based on expanded application of high-throughput in vitro screening and in silico methods to assess potential health risks of environmental agents. This review examines progress on the vision for toxicity testing elaborated by the US National Research Council (NRC) during the decade that has passed since the 2007 NRC report on Toxicity Testing in the 21st Century (TT21C). Concomitant advances in exposure assessment, including computational approaches and high-throughput exposomics, are also documented. A vision for the next generation of risk science, incorporating risk assessment methodologies suitable for the analysis of new toxicological and exposure data, resulting in human exposure guidelines is described. Case study prototypes indicating how these new approaches to toxicity testing, exposure measurement, and risk assessment are beginning to be applied in practice are presented. Overall, progress on the 20-year transition plan laid out by the US NRC in 2007 has been substantial. Importantly, government agencies within the United States and internationally are beginning to incorporate the new approach methodologies envisaged in the original TT21C vision into regulatory practice. Future perspectives on the continued evolution of toxicity testing to strengthen regulatory risk assessment are provided.

The advent of new testing systems and “omics”-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose effects, endocrine effects or nanotoxicology, while promising faster and more efficient toxicity testing with the use of less animals. Consequently, the respective assays, methods and testing strategies are subject of several research programs worldwide. On the other hand, the practical application of such tests for regulatory purposes is a matter of ongoing debate. This document summarizes key aspects of this debate in the light of the European “regulatory status quo ”, while elucidating new perspectives for regulatory toxicity testing.

Background: Diverse perspectives have influenced fish consumption choices. Objectives: We summarized the issue of fish consumption choice from toxicological, nutritional, ecological, and economic points of view; identified areas of overlap and disagreement among these viewpoints; and reviewed effects of previous fish consumption advisories. Methods: We reviewed published scientific literature, public health guidelines, and advisories related to fish consumption, focusing on advisories targeted at U.S. populations. However, our conclusions apply to groups having similar fish consumption patterns. Discussion: There are many possible combinations of matters related to fish consumption, but few, if any, fish consumption patterns optimize all domains. Fish provides a rich source of protein and other nutrients, but because of contamination by methylmercury and other toxicants, higher fish intake often leads to greater toxicant exposure. Furthermore, stocks of wild fish are not adequate to meet the nutrient demands of the growing world population, and fish consumption choices also have a broad economic impact on the fishing industry. Most guidance does not account for ecological and economic impacts of different fish consumption choices. Conclusion: Despite the relative lack of information integrating the health, ecological, and economic impacts of different fish choices, clear and simple guidance is necessary to effect desired changes. Thus, more comprehensive advice can be developed to describe the multiple impacts offish consumption. In addition, policy and fishery management interventions will be necessary to ensure long-term availability offish as an important source of human nutrition.

Introduction As chimeric antigen receptor T-cell therapies are becoming increasingly available in the armamentarium of the hematologist, there is an emerging need to monitor post-marketing safety. Objective We aimed to better characterize their safety profile by focusing on cytokine release syndrome and identifying emerging signals. Methods We queried the US Food and Drug Administration Adverse Event Reporting System (October 2017–September 2020) to analyze suspected adverse drug reactions to tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Disproportionality analyses (reporting odds ratio) were performed by comparing chimeric antigen receptor T-cell therapies with (a) all other drugs (reference group 1) and (b) other onco-hematological drugs with a similar indication, irrespective of age (reference group 2), or (c) restricted to adults (reference group 3). Notoriety was assessed through package inserts and risk management plans. Adverse drug reaction time to onset and cytokine release syndrome features were investigated. Results Overall, 3225 reports (1793 axi-cel; 1433 tisa-cel) were identified. The reported toxicities were mainly: cytokine release syndrome (52.2%), febrile disorders (27.7%), and neurotoxicity (27.2%). Cytokine release syndrome and neurotoxicity were often co-reported and 75% of the events occurred in the first 10 days. Disproportionalities confirmed known adverse drug reactions and showed unexpected associations: for example, axi-cel with cardiomyopathies (reporting odds ratio = 2.3; 95% confidence interval 1.2–4.4) and gastrointestinal perforations (2.9; 1.2–7.3), tisa-cel with hepatotoxicity (2.5; 1.1–5.7) and pupil disorders (15.3; 6–39.1). Conclusions Our study confirms the well-known adverse drug reactions and detects potentially emerging safety issues specific for each chimeric antigen receptor T-cell therapy, also providing insights into a stronger role for tisa-cel in inducing some immunodeficiency-related events (e.g., hypogammaglobulinemia, infections) and coagulopathies, and for axi-cel in neurotoxicity.

Di-2-ethylhexyl terephthalate (DEHTP), a structural isomer of di-2-ethylhexyl phthalate (DEHP), is a plasticizer used in a variety of commercial applications, but data on Americans’ exposure to DEHTP do not exist. We investigated the exposure to DEHTP in a convenience group of U.S. adults by analyzing urine collected anonymously in 2000 ( N  = 44), 2009 ( N  = 61), 2011 ( N  = 81), 2013 ( N  = 92), and 2016 ( N  = 149) for two major DEHTP oxidative metabolites: mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and mono-2-ethyl-5-hydroxyhexyl terephthalate (MEHHTP). For comparison, we also quantified the analogous DEHP metabolites mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) and mono-2-ethyl-5-carboxypentyl phthalate (MECPP). We detected MECPTP, MEHHP, and MECPP in all samples collected in 2016 with geometric means of 13.1, 4.1, and 6.7 ng/mL, respectively; we detected MEHHTP in 91% of the samples (geometric mean = 3.1 ng/mL). Concentrations of MECPTP correlated well with those of MEHHTP ( R 2  = 0.8, p  < 0.001), but did not significantly correlate with those of MEHHP ( p  > 0.05) suggesting different sources of exposure to DEHP and DEHTP. We also evaluated the fraction of the metabolites eliminated in their free (i.e., unconjugated) form. The median percent of unconjugated species was lower for the DEHP metabolites (MECPP [45.5%], MEHHP [1.9%]) compared to the DEHTP metabolites (MECPTP [98.8%], MEHHTP [21.2%]). Contrary to the downward trend from 2000 to 2016 in urinary concentrations of MEHHP and MECPP, we observed an upward trend for MEHHTP and MECPTP. These preliminary data suggest that exposure to DEHTP may be on the rise. Nevertheless, general population exposure data using MEHHTP and MECPTP as exposure biomarkers would increase our understanding of exposure to DEHTP, one of the known DEHP alternatives.

Air pollution disparities by socioeconomic status (SES) are well documented for the United States, with most literature indicating an inverse relationship (i.e., higher concentrations for lower-SES populations). Few studies exist for China, a country accounting for 26% of global premature deaths from ambient air pollution. Our objective was to test the relationship between ambient air pollution exposures and SES in China. We combined estimated year 2015 annual-average ambient levels of nitrogen dioxide ( ) and fine particulate matter [PM in aerodynamic diameter ( )] with national demographic information. Pollution estimates were derived from a national empirical model for China at spatial resolution; demographic estimates were derived from national gridded gross national product (GDP) per capita at resolution, and (separately) a national representative sample of 21,095 individuals from the China Health and Retirement Longitudinal Study (CHARLS) 2015 cohort. Our use of global data on population density and cohort data on where people live helped avoid the spatial imprecision found in publicly available census data for China. We quantified air pollution disparities among individual's rural-to-urban migration status; SES factors (education, occupation, and income); and minority status. We compared results using three approaches to SES measurement: individual SES score, community-averaged SES score, and gridded GDP per capita. Ambient and levels were higher for higher-SES populations than for lower-SES population, higher for long-standing urban residents than for rural-to-urban migrant populations, and higher for the majority ethnic group (Han) than for the average across nine minority groups. For the three SES measurements (individual SES score, community-averaged SES score, gridded GDP per capita), a 1-interquartile range higher SES corresponded to higher concentrations of and ; average concentrations for the highest and lowest 20th percentile of SES differed by 41-89% for and 12-25% for . This pattern held in rural and urban locations, across geographic regions, across a wide range of spatial resolution, and for modeled vs. measured pollution concentrations. Multiple analyses here reveal that in China, ambient and concentrations are higher for high-SES than for low-SES individuals; these results are robust to multiple sensitivity analyses. Our findings are consistent with the idea that in China's current industrialization and urbanization stage, economic development is correlated with both SES and air pollution. To our knowledge, our study provides the most comprehensive picture to date of ambient air pollution disparities in China; the results differ dramatically from results and from theories to explain conditions in the United States. https://doi.org/10.1289/EHP9872.