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Over the past 30 years, risk assessment has developed into a scientific discipline. It is critical that the next generation of risk assessors understand the history of our field, and recognize the numerous successes and failures that have taken place. This short Perspective identifies and describes specific books, monographs, and reports that are required reading for any nascent risk assessor. [ABSTRACT FROM AUTHOR]

Toxic chemicals - "toxicants" - have been studied and regulated as single entities, and, carcinogens aside, almost all toxicants, single or mixed and however altered, have been thought harmless in very low doses or very weak concentrations. Yet much work in recent decades has shown that toxicants can injure wildlife, laboratory animals, and humans following exposures previously expected to be harmless. Additional work has shown that toxicants can act not only individually and cumulatively but also collectively and even synergistically and that they affect disadvantaged communities inordinately - and therefore, as argued by reformers, unjustly. As late as December 2016, the last full month before the inauguration of a president promising to rescind major environmental regulations, the United States federal environmental-health establishment, as led by the Environmental Protection Agency (EPA), had not developed coherent strategies to mitigate such risks, to alert the public to their plausibility, or to advise leadership in government and industry about their implications. To understand why, we examined archival materials, reviewed online databases, read internal industry communications, and interviewed experts. We confirmed that external constraints, statutory and judicial, had been in place prior to EPA's earliest interest in mixture toxicity, but we found no overt effort, certainly no successful effort, to loosen those constraints. We also found internal constraints: concerns that fully committing to the study of complex mixtures involving numerous toxicants would lead to methodological drift within the toxicological community and that trying to act on insights from such study could lead only to regulatory futility. Interaction of these constraints, external and internal, shielded the EPA by circumscribing its responsibilities and by impeding movement toward paradigmatic adjustment, but it also perpetuated scientifically dubious policies, such as those limiting the evaluation of commercial chemical formulations, including pesticide formulations, to only those ingredients said by their manufacturers to be active. In this context, regulators' disregard of synergism contrasted irreconcilably with biocide manufacturers' understanding that synergism enhanced lethality and patentability. In the end, an effective national response to mixture toxicity, cumulative risk, and environmental injustice did not emerge. In parallel, though, the National Institute of Environmental Health Sciences, which was less constrained, pursued with scientific investigation what the EPA had not pursued with regulatory action., (© 2021. The Author(s).)

One-fifth of the way through the 21st century, a commonality of factors with those of the last 50 years may offer the opportunity to address unfinished business and current challenges. The recommendations include: (1) Resisting the tendency to oversimplify scientific assessments by reliance on single disciplines in lieu of clear weight-of-evidence expressions, and on single quantitative point estimates of health protective values for policy decisions; (2) Improving the separation of science and judgment in risk assessment through the use of clear expressions of the range of judgments that bracket protective quantitative levels for public health protection; (3) Use of comparative risk to achieve the greatest gains in health and the environment; and (4) Where applicable, reversal of the risk assessment and risk management steps to facilitate timely and substantive improvements in public health and the environment. Lessons learned and improvements in the risk assessment process are applied to the unprecedented challenges of the 21st century such as, pandemics and climate change. The beneficial application of the risk assessment and risk management paradigm to ensure timely research with consistency and transparency of assessments is presented. Institutions with mandated stability and leadership roles at the national and international levels are essential to ensure timely interdisciplinary scientific assessment at the interface with public policy as a basis for organized policy decisions, to meet time sensitive goals, and to inform the public., (© 2020 Society for Risk Analysis.)

Before the founding of the Society for Risk Analysis (SRA) in 1980, food safety in the United States had long been a concern, but there was a lack of systematic methods to assess food-related risks. In 1906, the U.S. Congress passed, and President Roosevelt signed, the Pure Food and Drug Act and the Meat Inspection Act to regulate food safety at the federal level. This Act followed the publication of multiple reports of food contamination, culminating in Upton Sinclair's novel The Jungle, which highlighted food and worker abuses in the meatpacking industry. Later in the 20th century, important developments in agricultural and food technology greatly increased food production. But chemical exposures from agricultural and other practices resulted in major amendments to federal food laws, including the Delaney Clause, aimed specifically at cancer-causing chemicals. Later in the 20th century, when quantitative risk assessment methods were given greater scientific status in a seminal National Research Council report, food safety risk assessment became more systematized. Additionally, in these last 40 years, food safety research has resulted in increased understanding of a range of health effects from foodborne chemicals, and technological developments have improved U.S. food safety from farm to fork by offering new ways to manage risks. We discuss the history of food safety and the role risk analysis has played in its evolution, starting from over a century ago, but focusing on the last 40 years. While we focus on chemical risk assessment in the U.S., we also discuss microbial risk assessment and international food safety., (© 2020 Society for Risk Analysis.)

After World War II, organized tackle football programs for boys younger than high school age grew enormously in popularity in the United States, prompting concerns from pediatricians and educators about the sport's physical and emotional health effects. At the same time, sports medicine was emerging as a sub-specialty. Examining how American sports medicine doctors and football coaches established their professional authority on youth football safety in the 1950s and 1960s reveals how their justifications for this collision sport were connected to broader cultural trends. Doctors and coaches, who were virtually all men, emphasized their firsthand knowledge of an all-male sport that was widely promoted as a means of teaching boys to become men. They insisted that proper supervision and equipment were sufficient to protect young athletes. Their arguments for youth football's benefits were based on the belief that men best knew how to impart desired values such as loyalty, patriotism and discipline to boys. In framing football's health risks as manageable with adult supervision, coaches and sports medicine doctors played a crucial role in promoting the vision of American manhood associated with tackle football., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This paper reviews the research programme that went into the development of FRAX® and its impact in the 10 years since its release in 2008., Introduction: Osteoporosis is defined on the measurement of bone mineral density though the clinical consequence is fracture. The sensitivity of bone mineral density measurements for fracture prediction is low, leading to the development of FRAX to better calculate the likelihood of fracture and target anti-osteoporosis treatments., Methods: The method used in this paper is literature review., Results: FRAX, developed over an 8-year period, was launched in 2008. Since the launch of FRAX, models have been made available for 64 countries and in 31 languages covering more than 80% of the world population., Conclusion: FRAX provides an advance in fracture risk assessment and a reference technology platform for future improvements in performance characteristics.

Human biomonitoring is the foundation of environmental toxicology, community public health evaluation, preclinical health effects assessments, pharmacological drug development and testing, and medical diagnostics. Within this framework, the intra-class correlation coefficient (ICC) serves as an important tool for gaining insight into human variability and responses and for developing risk-based assessments in the face of sparse or highly complex measurement data. The analytical procedures that provide data for clinical and public health efforts are continually evolving to expand our knowledge base of the many thousands of environmental and biomarker chemicals that define human systems biology. These chemicals range from the smallest molecules from energy metabolism (i.e., the metabolome), through larger molecules including enzymes, proteins, RNA, DNA, and adducts. In additiona, the human body contains exogenous environmental chemicals and contributions from the microbiome from gastrointestinal, pulmonary, urogenital, naso-pharyngeal, and skin sources. This complex mixture of biomarker chemicals from environmental, human, and microbiotic sources comprise the human exposome and generally accessed through sampling of blood, breath, and urine. One of the most difficult problems in biomarker assessment is assigning probative value to any given set of measurements as there are generally insufficient data to distinguish among sources of chemicals such as environmental, microbiotic, or human metabolism and also deciding which measurements are remarkable from those that are within normal human variability. The implementation of longitudinal (repeat) measurement strategies has provided new statistical approaches for interpreting such complexities, and use of descriptive statistics based upon intra-class correlation coefficients (ICC) has become a powerful tool in these efforts. This review has two parts; the first focuses on the history of repeat measures of human biomarkers starting with occupational toxicology of the early 1950s through modern applications in interpretation of the human exposome and metabolic adverse outcome pathways (AOPs). The second part reviews different methods for calculating the ICC and explores the strategies and applications in light of different data structures.

After 40 years, the 1976 US Toxic Substances Control Act (TSCA) was revised under the Frank R. Lautenberg Chemical Safety for the 21st Century Act. Its original goals of protecting the public from hazardous chemicals were hindered by complex and cumbersome administrative burdens, data limitations, vulnerabilities in risk assessments, and recurring corporate lawsuits. As a result, countless chemicals were entered into commercial use without toxicological information. Few chemicals of the many identified as potential public health threats were regulated or banned. This paper explores the factors that have worked against a comprehensive and rational policy for regulating toxic chemicals and discusses whether the TSCA revisions offer greater public protection against existing and new chemicals.

Bone densitometry (dual energy x-ray absorptiometry-DXA) is a vital medical tool needed for the diagnosis of osteoporosis in non-fractured patients; predicting future fracture risk; and monitoring bone mineral density (BMD) in untreated or treated patients. The history of the pivotal international society involved in the science and clinical interpretation of DXA, the International Society for Clinical Densitometry (ISCD) is defined in this manuscript. Since DXA and Osteoporosis management are intimately linked, the ISCD has over the years developed strong bonds with both the National Osteoporosis Foundation (NOF) and the International Osteoporosis Foundation (IOF). The positive impact that ISCD has led in the proper performance and clinical interpretation of bone mass measurements has been enormous worldwide., (Copyright © 2017. Published by Elsevier Inc.)

The LNT single-hit model was derived from the Nobel Prize-winning research of Herman J. Muller who showed that x-rays could induce gene mutations in Drosophila and that the dose response for these so-called mutational events was linear. Lewis J. Stadler, another well-known and respected geneticist at the time, strongly disagreed with and challenged Muller's claims. Detailed evaluations by Stadler over a prolonged series of investigations revealed that Muller's experiments had induced gross heritable chromosomal damage instead of specific gene mutations as had been claimed by Muller at his Nobel Lecture. These X-ray-induced alterations became progressively more frequent and were of larger magnitude (more destructive) with increasing doses. Thus, Muller's claim of having induced discrete gene mutations represented a substantial speculative overreach and was, in fact, without proof. The post hoc arguments of Muller to support his gene mutation hypothesis were significantly challenged and weakened by a series of new findings in the areas of cytogenetics, reverse mutation, adaptive and repair processes, and modern molecular methods for estimating induced genetic damage. These findings represented critical and substantial limitations to Muller's hypothesis of X-ray-induced gene mutations. Furthermore, they challenged the scientific foundations used in support of the LNT single-hit model by severing the logical nexus between Muller's data on radiation-induced inheritable alterations and the LNT single-hit model. These findings exposed fundamental scientific flaws that undermined not only the seminal recommendation of the 1956 BEAR I Genetics Panel to adopt the LNT single-hit Model for risk assessment but also any rationale for its continued use in the present day., (Copyright © 2017 Elsevier Inc. All rights reserved.)

There are both statistically valid and invalid reasons why scientists with differing default hypotheses can disagree in high-profile situations. Examples can be found in recent correspondence in this journal, which may offer lessons for resolving challenges to mainstream science, particularly when adherents of a minority view attempt to elevate the status of outlier studies and/or claim that self-interest explains the acceptance of the dominant theory. Edward J. Calabrese and I have been debating the historical origins of the linear no-threshold theory (LNT) of carcinogenesis and its use in the regulation of ionizing radiation. Professor Calabrese, a supporter of hormesis, has charged a committee of scientists with misconduct in their preparation of a 1956 report on the genetic effects of atomic radiation. Specifically he argues that the report mischaracterized the LNT research record and suppressed calculations of some committee members. After reviewing the available scientific literature, I found that the contemporaneous evidence overwhelmingly favored a (genetics) LNT and that no calculations were suppressed. Calabrese's claims about the scientific record do not hold up primarily because of lack of attention to statistical analysis. Ironically, outlier studies were more likely to favor supra-linearity, not sub-linearity. Finally, the claim of investigator bias, which underlies Calabrese's accusations about key studies, is based on misreading of text. Attention to ethics charges, early on, may help seed a counter narrative explaining the community's adoption of a default hypothesis and may help focus attention on valid evidence and any real weaknesses in the dominant paradigm., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper brings together the history of risk and the history of DNA repair, a biological phenomenon that emerged as a research field in between molecular biology, genetics, and radiation research in the 1960s. The case of xeroderma pigmentosum (XP), an inherited hypersensitivity to UV light and, hence, a disposition to skin cancer will be the starting point to argue that, in the 1970s and 1980s, DNA repair became entangled in the creation of new models of the human body at risk - what is here conceptually referred to as the vulnerability aspect of body history - and new attempts at cancer prevention and enhancement of the body associated with the new flourishing research areas of antimutagenesis and anticarcinogenesis. The aim will be to demonstrate that DNA repair created special attempts at disease prevention: molecular enhancement, seeking to identify means to increase the self-repair abilities of the body at the molecular level. Prevention in this sense meant enhancing the body's ability to cope with the environmental hazards of an already toxic world. This strategy has recently been adopted by the beauty industry, which introduced DNA care as a new target for skin care research and anti-aging formulas.

Health risk assessments provide an opportunity to emphasise health promotion and disease prevention for individuals and populations at large. A key component of health risk assessments is the detailed collection of family health history information. This information is helpful in determining risk both for common chronic conditions and more rare diseases as well. While the concept of health risk assessments has been around since the Framingham Heart Study was launched in the 1950s, and such assessments are commonly performed in the workplace today, the US healthcare system has been slow to embrace them and the emphasis on prevention that they represent. Before wider implementation of health risk assessments within healthcare can be seen, several concerns must be addressed: (1) provider impact, (2) patient impact, (3) validity of patient-entered data and (4) health outcomes effect. Here, we describe recent developments in health risk assessment design that are helping to address these issues., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: Since Doll published the first PAF in 1951, it has been a mainstay. Confusion in terminology abounds with regard to these measures. The ability to estimate all of them in case-control studies as well as in cohort studies is not widely appreciated., Methods: This article reviews and comments on the historical development of the population attributable fraction (PAF), the exposed attributable fraction (EAF), the rate difference (ID), the population rate (or incidence) difference (PID), and the caseload difference (CD)., Results: The desire for PAFs to sum to no more than 100% and the interpretation of the complement of a PAF as the proportion of a rate that can be attributed to other causes are shown to stem from the same problem: a failure to recognize the pervasiveness of shared etiologic responsibility among causes. A lack of appreciation that "expected" numbers of cases and deaths are not actually the numbers to be expected when an exposure or intervention appreciably affects person-time denominators for rates, as in the case of smoking and nonnormal body mass, makes many CD estimates inflated. A movement may be gaining momentum to shift away from assuming, often unrealistically, the complete elimination of harmful exposures and toward estimating the effects of realistic interventions. This movement could culminate in a merger of the academic concept of transportability with the applied discipline of risk assessment., Conclusions: A suggestion is offered to pay more attention to absolute measures such as the rate difference, the population rate difference, and the CD, when the latter can be validly estimated and less attention to proportional measures such as the EAF and PAF., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This paper identifies the origin of the linearity at low-dose concept [i.e., linear no threshold (LNT)] for ionizing radiation-induced mutation. After the discovery of X-ray-induced mutations, Olson and Lewis (Nature 121(3052):673-674, 1928) proposed that cosmic/terrestrial radiation-induced mutations provide the principal mechanism for the induction of heritable traits, providing the driving force for evolution. For this concept to be general, a LNT dose relationship was assumed, with genetic damage proportional to the energy absorbed. Subsequent studies suggested a linear dose response for ionizing radiation-induced mutations (Hanson and Heys in Am Nat 63(686):201-213, 1929; Oliver in Science 71:44-46, 1930), supporting the evolutionary hypothesis. Based on an evaluation of spontaneous and ionizing radiation-induced mutation with Drosophila, Muller argued that background radiation had a negligible impact on spontaneous mutation, discrediting the ionizing radiation-based evolutionary hypothesis. Nonetheless, an expanded set of mutation dose-response observations provided a basis for collaboration between theoretical physicists (Max Delbruck and Gunter Zimmer) and the radiation geneticist Nicolai Timoféeff-Ressovsky. They developed interrelated physical science-based genetics perspectives including a biophysical model of the gene, a radiation-induced gene mutation target theory and the single-hit hypothesis of radiation-induced mutation, which, when integrated, provided the theoretical mechanism and mathematical basis for the LNT model. The LNT concept became accepted by radiation geneticists and recommended by national/international advisory committees for risk assessment of ionizing radiation-induced mutational damage/cancer from the mid-1950s to the present. The LNT concept was later generalized to chemical carcinogen risk assessment and used by public health and regulatory agencies worldwide.

About 50 years ago, Norman Jefferis Holter invented a device that opened the possibility of recording heart activity over long periods of time. This invention, together with the rapid developments in electronics, has enabled a revolutionary change in the diagnosis and management of cardiac diseases. Ambulatory cardiac monitors have decreased in size to the point of becoming wearable or implantable and are able to monitor heart activity for months or even years. In addition, new telecommunication systems allow clinicians to remotely access cardiac events and to respond within a short period of time. Novel advances in computing and algorithm development are expanding the clinical applications of ambulatory devices with more complex automatic interpretation of the electrocardiographic signal. This article reviews the state of the art of these techniques from both clinical and technical approaches, covering a historic perspective up to today, and discusses current applications, challenges, and future directions.

This paper reviews how aerosol exposure assessment, for people in both working and living environments, has evolved over the years. It charts the main scientific developments that led to progressively improved ways of thinking and methods to assess exposure to airborne particulate matter in a manner more relevant to human health. It has been a long scientific journey as one generation of pioneering contributors has handed off to the next. In the process a consistent rationale has emerged, producing aerosol sampling criteria--and in turn exposure standards--which have been increasingly relevant to actual human exposures. The journey continues as a new generation of scientists steps up to deal with the new challenges that are emerging. An appreciation of the history of what went before is essential to charting the most effective path looking forward.

The International Radioecology Laboratory (IRL) located in Slavutych, Ukraine, was created in 1999 under the initiative of the United States Government and the Government of Ukraine in the framework of international cooperation on evaluation and minimization of consequences of the Chernobyl nuclear power plant (ChNPP) accident. Since the time the IRL was founded, it has participated in a large number of projects, including the following: 1) study of radionuclide accumulation, distribution, and migration in components of various ecological systems of the Chernobyl Exclusion Zone (ChEZ); 2) radiation dose assessments; 3) study of the effects of radiation influence on biological systems; 4) expert analysis of isotopic and quantitative composition of radioactive contaminants; 5) development of new methods and technologies intended for radioecological research; 6) evaluation of future developments and pathways for potential remediation of the ChEZ areas; 7) assistance in provision of physical protection systems for ionizing irradiation sources at Ukrainian enterprises; 8) reviews of open Russian language publications on issues associated with consequences of the ChNPP accident, radioactive waste management, radioecological monitoring, and ChNPP decommissioning; 9) conduct of training courses on problems of radioecology, radiation safety, radioecological characterization of test sites and environmental media, and research methods; 10) conduct of on-site scientific conferences and workshops on the ChEZ and radioecology problems; participation in off-site scientific conferences and meetings; and 11) preparation of scientific and popular science publications and interactions with mass media representatives. This article provides a brief overview of the major achievements resulting from this cooperation between the IRL and U.S. research centers.

There is an increasing need for a quick, simple method to represent diurnal population change in metropolitan areas for effective emergency management and risk analysis. Many geographic studies rely on decennial U.S. Census data that assume that urban populations are static in space and time. This has obvious limitations in the context of dynamic geographic problems. The U.S. Department of Transportation publishes population data at the transportation analysis zone level in fifteen-minute increments. This level of spatial and temporal detail allows for improved dynamic population modeling. This article presents a methodology for visualizing and analyzing diurnal population change for metropolitan areas based on this readily available data. Areal interpolation within a geographic information system is used to create twenty-four (one per hour) population surfaces for the larger metropolitan area of Salt Lake County, Utah. The resulting surfaces represent diurnal population change for an average workday and are easily combined to produce an animation that illustrates population dynamics throughout the day. A case study of using the method to visualize population distributions in an emergency management context is provided using two scenarios: a chemical release and a dirty bomb in Salt Lake County. This methodology can be used to address a wide variety of problems in emergency management.

I formulate a simple and parsimonious evolutionary model that shows that because most species face a possibility of dying because of external factors, called extrinsic mortality in the biology literature, it can simultaneously explain (a) why we discount the future, (b) get weaker with age, and (c) display risk-aversion. The paper suggests that testable restrictions—across species, across time, or across genders—among time preference, aging, and risk-aversion could be analyzed in a simple framework .

Deposition densities (Bq m(-2)) of all important dose-contributing radionuclides occurring in nuclear weapons testing fallout from tests conducted at Bikini and Enewetak Atolls (1946-1958) have been estimated on a test-specific basis for 32 atolls and separate reef islands of the Marshall Islands. A complete review of various historical and contemporary data, as well as meteorological analysis, was used to make judgments regarding which tests deposited fallout in the Marshall Islands and to estimate fallout deposition density. Our analysis suggested that only 20 of the 66 nuclear tests conducted in or near the Marshall Islands resulted in substantial fallout deposition on any of the 23 inhabited atolls. This analysis was confirmed by the fact that the sum of our estimates of 137Cs deposition from these 20 tests at each atoll is in good agreement with the total 137Cs deposited as estimated from contemporary soil sample analyses. The monitoring data and meteorological analyses were used to quantitatively estimate the deposition density of 63 activation and fission products for each nuclear test, plus the cumulative deposition of 239+240Pu at each atoll. Estimates of the degree of fractionation of fallout from each test at each atoll, as well as of the fallout transit times from the test sites to the atolls were used in this analysis. The estimates of radionuclide deposition density, fractionation, and transit times reported here are the most complete available anywhere and are suitable for estimations of both external and internal dose to representative persons as described in companion papers.

Some of the best-known social scientific theories of risks are those that have been elaborated by Anthony Giddens and Ulrich Beck. Although their arguments differ greatly, they agree in seeing the technologically induced risks of today's "Risk Society" as global - so pervasive that they transcend all socioeconomic as well as geopolitical and national boundaries. Most empirical work, however, provides greater support for a theoretical tradition exemplified by Short and Erikson. In this paper, we argue that many of the technological mega-risks described by Giddens and Beck as "transcending" social boundaries are better described as "Titanic risks," referring not so much to their colossal impact as to the fact that - as was the case for the majority of the victims on the Titanic - actual risks are related to victims' socioeconomic as well as sociogeographic locations. Previous research has shown this to be the case with high-risk technologies, such as nuclear energy and weaponry, and also with localized ones, such as toxic waste disposal. This article illustrates that the same is true even for the most genuinely "global" risks of all, namely those associated with global climate disruption.

This paper examines the contributions made by early modern statistical literature to the formation of the sociological imagination. Starting in the mid-seventeenth century, the fields of 'political arithmetic' and vital and moral statistics provided a discursive framework within which it became possible to identify and study aggregate dynamics and structures underlying seemingly random and episodic aspects of life (birth, death, divorce, health). Focusing primarily on developments in England, the paper identifies three significant watershed moments in the emergence of the sociological imagination: the discovery of the political and economic dimensions of life; the articulation of socio-statistical patterns underlying various life events and episodes; and the establishment of causal connections between social variables and individual choices. These developments did not amount to or directly result in the creation of the discipline of sociology, yet, they made it possible to make conceptual connections between the personal and the social.

This article assesses the historical foundations of how linearity at low dose became accepted by the scientific/regulatory communities. While the threshold model was used in the 1920s/1930s in establishing radiation health standards, its foundations were challenged by the genetics community who argued that radiation induced mutations in reproductive cells followed a linear response, were cumulative and deleterious. Scientific foundations of linearity for gonadal mutations were based on non-conclusive evidence as well as not being conducted at low doses. Following years of debate, leaders in the genetics community participated in the U.S. National Academy of Sciences (NAS) (1956) Biological Effects of Atomic Radiation (BEAR) BEAR I Committee, getting their perspectives accepted, incorporating linearity for radiation-induced mutational effects in risk assessment. Overtime the concept of linearity was generalized to include somatic effects induced by radiation based on a protectionist philosophy. This affected the course of radiation-induced and later chemically-induced carcinogen risk assessment. Acceptance of linearity at low dose from chemical carcinogens was strongly influenced by the NAS Safe Drinking Water Committee report of 1977 which provided the critical guidance to the U.S. EPA to adopt linear at low dose modeling for risk assessment for chemical carcinogens with little supportive data, much of which has been either discredited or seriously weakened over the past 3 decades. Nonetheless, there has been little practical change of regulatory policy concerning carcinogen risk assessment. These observations suggest that while scientific disciplines are self correcting, that regulatory 'science' fails to display the same self-correcting mechanism despite contradictory data.

The first remarkable adverse drug reaction (ADR) reported in Japan was anaphylactic shock caused by penicillin. Although intradermal testing for antibiotics had been exercised as prediction method of anaphylactic shock for a long time, it was discontinued in 2004 because of no evidence for prediction. The malformation of limbs, etc. caused by thalidomide was a global problem, and thalidomide was withdrawn from the market. Teratogenicity testing during new drug development has been implemented since 1963. Chinoform (clioquinol)-iron chelate was detected from green tongue and green urine in patients with subacute myelo-optic neuropathy (SMON) and identified as a causal material of SMON in 1970. Chinoform was withdrawn from the market, and a fund for relief the health damage caused by ADR was established in 1979. The co-administration of sorivudine and fluorouracil anticancer agents induced fatal agranulocytosis, and sorivudine was withdrawn from the market after being on sale for one month in 1993. The guidelines for package inserts were corrected with this opportunity, and early phase pharmacovigilance of new drugs was introduced later. Since acquired immune deficiency syndrome, and hepatitis B and C were driven by virus-infected blood products, the Ministry of Health, Labor and Welfare tightened regulations regarding biological products in 2003, and a fund for relief of health damage caused by infections driven from biological products was established in 2004. The other remarkable ADRs were quadriceps contracture induced by the repeated administration of muscular injection products and Creutzfeldt-Jakob disease caused by the transplantation of human dry cranial dura matter, etc. The significance of safety measures for drugs based on experiences related to ADRs is worthy of notice. New drugs are approved based on a benefit-risk assessment, if the expected therapeutic benefits outweigh the possible risks associated with treatment. Since unexpected, rare and serious ADRs have been detected after administration to many patients in the post-marketing stage, risk management is required for product life-cycle management.

Editor's Note: This is 1 of 4 papers from the US Environmental Protection Agency Science Advisory Board's Ecological Processes and Effects Committee workshop on the current and future practice of ecological risk assessment. The workshop was held in Washington, DC in February 2006. Risk assessment originated with the insurance industry and spread to the estimation of risks to people and property in other contexts, including the regulation of environmental contamination. Ecological assessment became an important component of environmental management in the United States with the legal mandate for environmental impact assessment in 1970. Risk assessment and ecological assessment merged in the 1980s to form ecological risk assessment (ERA). Since then, ERA has been institutionalized with the development of the US Environmental Protection Agency's (hereafter, USEPA or Agency) framework and guidance documents. Ecological risk assessment has been adapted by the Agency's program offices to fit their legal and policy contexts. The future of ERA will inevitably include the incorporation of more complex and demanding methods. However, the biggest challenge for future risk assessors will be to make ecological risks more compelling to decision makers.

An important factor in making a recommendation for treatment of a patient with arteriovenous malformation (AVM) is to estimate the risk of surgery for that patient. A simple, broadly applicable grading system that is designed to predict the risk of morbidity and mortality attending the operative treatment of specific AVM's is proposed. The lesion is graded on the basis of size, pattern of venous drainage, and neurological eloquence of adjacent brain. All AVM's fall into one of six grades. Grade I malformations are small, superficial, and located in non-eloquent cortex; Grade V lesions are large, deep, and situated in neurologically critical areas; and Grade VI lesions are essentially inoperable AVM's. Retrospective application of this grading scheme to a series of surgically excised AVM's has demonstrated its correlation with the incidence of postoperative neurological complications. The application of a standardized grading scheme will enable a comparison of results between various clinical series and between different treatment techniques, and will assist in the process of management decision-making.

This essay represents a serious but fictional obituary of a scientific concept called the Threshold Dose-Response Model, which has long dominated the fields of toxicology and the broader biomedical sciences. Recent evidence indicates that the Threshold Dose-Response Model has long outlived its utility to predict low-dose effects. In fact, so poorly does this model predict low-dose responses that the idea arose that it should receive a symbolic burial recounting its achievements and failings, hence this obituary., ((c) 2007 Wiley Periodicals, Inc.)

The basis for personal dosimetry performance testing in the United States is ANSI/HPS N13.11 (2001). Now in its third edition, this standard has been in place since 1983. Testing under this standard is administered by the National Voluntary Accreditation Program (NVLAP), and accreditation of dosimetry processors under this program is required by US Nuclear Regulatory Commission (NRC) regulations. The US Department of Energy (DOE) also maintains a testing program for its laboratories and contractors, administered by the Department of Energy Laboratory Accreditation Program (DOELAP). A focus in recent years has been the modification of ANSI/HPS N13.11 to allow acceptance by both testing programs in order to bring harmonisation to US personal dosemeter processing testing. Since there is no type testing program in the US for personal dosemeters, the testing philosophy of ANSI N13.11 has always combined elements of type testing and routine performance testing. This philosophy is explored in detail in this presentation, along with trends in the development of the document to its present state. In addition, a look will be taken at what the future holds for the next revision of the document, scheduled to begin in 2005.

Air quality is managed in Great Britain via an effects-based, risk management process designed to provide a dynamic solution to public health issues associated with elevated concentrations of seven specified air pollutants. This paper is concerned with an examination and evaluation of the process of Local Air Quality Management (LAQM) in Great Britain from the late 1980s to date as a risk management process. The statutory basis of LAQM process is provided by the Environment Act 1995. The Act provides a framework in which national and local actions are required to identify and remediate areas of poor air quality. Within this framework, the implementation of the process at national and local levels is considered, leading to an identification and assessment of risks in the formulation and implementation of air quality management policy and practice. Local Authorities began the process of Review and Assessment in 1999 and the first round of the process concluded in 2001. Following this, some 129 Local Authorities declared one or more Air Quality Management Areas (AQMAs). The Review and Assessment elements of the framework were subjected to an evaluation in 2001 and the essential elements of it were confirmed as fit for purpose. The evaluation led to a confirmation of the process of LAQM but also a simplification based on the experience of Round 1. Now, a two step process is required comprising of an Updating and Screening Assessment and, where a risk of exceeding an Air Quality Objective (AQO) is identified, a Detailed Assessment follows. The Government has identified a time scale for Review and Assessment through to 2010 and also introduced the requirement of a regular Progress Report in order that a Local Authority is able to address routine matters of air quality management. The risks inherent in epidemiological or scientific uncertainty are factored into the LAQM process at an early stage of the process and, by identifying the risks and subjecting them to regular review, the process provides a 'level playing field' across spatial and temporal scales. Whilst the process of LAQM described in this paper has been developed for Great Britain, the generic elements of the process are applicable to other countries challenged by air pollution problems which require both national and local action to resolve them.

Special observation by mental health professionals is the recommended approach for those people deemed as at risk or risky. Recent research and academic writing have challenged the benefits of observing people/patients who are defined as 'at risk', and a more human engagement process is being recommended. Despite this assault, practice has not changed substantively, suggesting a need for a thorough exploration and questioning of the practices and process. The paper outlines three Foucaultian approaches to historical analysis. It applies aspects of Foucault's archaeology/genealogy, discourse and power/knowledge to explore the practices of special observation as a means of controlling risk, especially suicide risk. We identify the regulatory function of the 'gaze', professional codes and government policy in relation to restricting professional practices. We argue that observation can be related to moral therapy, wherein the person relinquishes madness for responsibility through a disciplinary process and, in governing risk, a 'professional industry' is created. The regulation of statements about people with mental health issues are exposed and related to what can be said and done by professionals. Finally, we look at productive power in relation to observation, and how it is intimately related to resistance. We conclude with 'soft' recommendations for practice discursively produced through the writing of the paper.

Since the discovery of fission, the notion of a chain reaction in a critical mass releasing massive amounts of energy has haunted physicists. The possibility of a bomb or a reactor prompted much of the early work on determining a critical mass, but the need to avoid an accidental critical excursion during processing or transport of fissile material drove much that took place subsequently. Because of the variety of possible situations that might arise, it took some time to develop adequate theoretical tools for criticality safety and the early assessments were based on direct experiment. Some extension of these experiments to closely similar situations proved possible, but it was not until the 1960s that theoretical methods (and computers to run them) developed enough for them to become reliable assessment tools. Validating such theoretical methods remained a concern, but by the end of the century they formed the backbone of criticality safety assessment. This paper traces the evolution of these methods, principally in the UK and USA, and summarises some related work concerned with the nature of criticality accidents and their radiological consequences. It also indicates how the results have been communicated and used in ensuring nuclear safety.