With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.

Scientists Appeal to Quebec Premier Charest to Stop Exporting Asbestos to the Developing World

Elsevier Science refused to publish a study of IBM workers that IBM sought to keep from public view. Occupational and environmental health (OEH) suffers from the absence of a level playing field on which science can thrive. Industry pays for a substantial portion of OEH research. Studies done by private consulting firms or academic institutions may be published if the results suit the sponsoring companies, or they may be censored. OEH journals often reflect the dominance of industry influence on research in the papers they publish, sometimes withdrawing or modifying papers in line with industry and advertising agendas. Although such practices are widely recognized, no fundamental change is supported by government and industry or by professional organizations.

Although many reproductive toxicants and carcinogens are used in the manufacture of semiconductor chips, and worrisome findings have been reported, no broad epidemiologic study has been conducted to define possible risks in a comprehensive way. With few exceptions, the American semiconductor industry has not supported access for independent studies. Older technologies are exported to newly industrialized countries as newer technologies are installed in Japan, the United States, and Europe. Thus there is particular concern about the many workers, mostly in countries that are still industrializing, who have jobs that use chemicals, technologies, and equipment that are no longer in use in developed countries. Since most countries lack cancer registries and have inadequate reproductive and cancer reporting mechanisms, industry efforts to control exposures to carcinogens are of particular importance. Government agencies, the courts, industry, publishers, and academia, on occasion, collude to ignore or to downplay the importance of occupational diseases. Examples of how this happens in the semiconductor industry are presented.

The confidence interval, its close cousin the p-value, and other statistical summaries of data are widely used in science, including the occupational and environmental health sciences, but they are almost as widely misused. My purpose here is to review some basic matters that should be covered in every introductory statistics course, but are generally omitted. More specifically, some of the many assumptions that are needed in the usual forms of analysis are reviewed.

The effect of dormitory environments on the transmission of the influenza virus in college students is not well understood. During the 1999-2000 flu season, dormitory residents at a college campus in Chicago were surveyed about their living conditions and influenza-like symptoms (ILS). The survey had a 42 percent response ratio (721 of 1,704). Students who had > or = 50 percent carpeting in their room were at significantly lower risk for ILS (p = .02). Although the risk of ILS increased for roommates who shared sleeping quarters compared with those who slept in different rooms (RR = 4.3), the difference was not statistically significant. No evidence was found that ILS risk was affected by washroom, laundry, or dining settings, or by demographics, including gender or year in college. The survey instrument detected strong relations between ILS and the dormitory room environment, in contrast with other settings in the dormitory. Further research on transmission may focus on the room environment.

The Precautionary Principle (PP) has recently been formally introduced into national and international law. The key element is the justification for acting in the face of uncertainty. The PP is thereby a tool for avoiding possible future harm associated with suspected, but not conclusive, environmental risks. Under the PP, the burden of proof is shifted from demonstrating the presence of risk to demonstrating the absence of risk and it is the responsibility of the producer of a technology to demonstrate its safety rather than the responsibility of public authorities to show harm. Past experiences show the costly consequences of disregarding early warnings about environmental hazards. Today, the need for applying the PP is even greater. New research is needed to expand current insight into disease causation, to elucidate the full scope of potential adverse implications resulting from environmental pollutants, and to identify opportunities for prevention. Research approaches should be developed and strengthened to counteract innate ideological biases and to support our confidence in applying the PP for decision-making in the public policy arena.

Epidemiologic work conducted over several decades has suggested that long-term residence in cities with elevated ambient levels of air pollution from combustion sources is associated with increased mortality. Subsequently, two prospective cohort studies, the Six Cities Study (as reported in Dockery et al., 1993) and the American Cancer Society (ACS) Study (as reported in Pope et al., 1995), estimated that annual average all-cause mortality increased in association with an increase in fine particles (all particles less than 2.5 µm in median aerodynamic diameter [PM2.5]). As part of the Six Cities Study, Dockery and colleagues (1993) had prospectively followed a cohort of 8111 adult subjects in the northeastern and midwestern United States for 14 to 16 years beginning in the mid-1970s. The authors found that higher ambient levels of fine particles and sulfate (SO ) were associated with a 26% increase in mortality from all causes when comparing the most polluted to the least polluted city and that an increase in fine particles was also associated with increased mortality from cardiopulmonary disease. The relative risks in all-cause mortality were associated with a difference (or range) in ambient fine particle concentrations of 18.6 µg/m 3 and a difference of ambient sulfate concentrations of 8.0 µg/m 3 , comparing the least polluted city to the most polluted city.

To our knowledge, no comprehensive risk assessment of agricultural uses of antimicrobial agents has been published. The published risk assessments of antimicrobial use in farm settings are all subject to multiple, serious limitations in scope, including (1) limitation to one species of microorganism; (2) limitation to one or a very few related antimicrobial agents; (3) limitation to a single outcome (death, hospital days, number of illnesses, etc.); (4) limitation to one species of farm animal (e. g., chicken or swine); and (5) limitation to therapeutic use, despite reason for concern about misstated, off-label, or illegal use. In addition, all of the risk assessments reviewed overlooked important issues by accepting 2 further limitations: (6) limiting the scope of the analysis to what has already happened and ignoring the effects of continuing the practices of recent years; and (7) examining only the effects on the species of microorganism that was initially affected and ignoring the cross-species spread of resistance by plasmid transfer. After our review of the risk assessments now available, we propose a comprehensive scheme for organizing existing knowledge and dealing with critical gaps.

The Agricultural Health Study (AHS) has approximately 90,000 pesticide applicators and their spouses enrolled in a number of studies to determine whether exposures to specific pesticides are associated with various cancers and other adverse health outcomes. Although the AHS was intended to be an integrated program of studies, some significant difficulties have emerged. In this report, we examine the design of the AHS, identify important program strengths and flaws, suggest various improvements in the program, and recommend ancillary studies that could be undertaken to strengthen the AHS. Overall, the AHS is collecting a large amount of information on potential determinants of health status among farmers and farm families. A promising feature of the AHS is the prospective cohort study of cancers among farmers in which the research design determines exposures prior to the diagnosis of disease. More effort needs to be devoted to reducing selection bias and information bias. Success of the cohort study will depend in part on follow-up surveys of the cohort to determine how exposures and disease states change as the cohort ages. The cross-sectional and case-control studies planned in the AHS are less promising because they will be subject to some of the same criticisms, such as potentially biased and imprecise exposure assessment, that have characterized the existing literature in this field. Important limitations of the AHS include low and variable rates of subject response to administered surveys, concerns about the validity of some self-reported non-cancer health outcomes, limited understanding of the reliability and validity of self-reporting of chemical use, an insufficient program of biological monitoring to validate the exposure surrogates employed in the AHS questionnaires, possible confounding by unmeasured, nonchemical risk factors for disease, and the absence of detailed plans for data analysis and interpretation that include explicit, a priori hypotheses. Although the AHS is already well underway, most of these limitations can be addressed by the investigators if adequate resources are made available. If these limitations are not addressed, the large amounts of data generated in the AHS will be difficult to interpret. If the exposure and health data can be validated, the scientific value of the AHS should be substantial and enduring. A variety of research recommendations are made to strengthen the AHS. They include reliability and validity studies of farmer reporting of chemical use, biological monitoring studies of farmers and members of farm families, and validity studies of positive and negative self-reports of disease status. Both industry and government should consider expanded research programs to strengthen the AHS.

Summary The Precautionary Principle has recently been formally in- troduced into national and international law. The key element is the justification for acting in the face of uncertainty. The Precautionary Principle is thereby a tool for avoiding possible future harm associated with suspected, but not conclusive, en- vironmental risks. Accordingly, the burden of proof is shifted from demonstrating the presence of risk to demonstrating the absence of risk. Past experience shows the costly conse- quences of disregarding early warnings about environmental hazards. Today, the need for applying the Precautionary Prin- ciple is even greater. New research is needed to expand cur- rent insight into disease causation, to elucidate the full scope of potential adverse implications resulting from environmen- tal pollutants, and to identify opportunities for prevention. Research approaches should be developed and strengthened to counteract innate ideological biases and to support our confidence in applying the Precautionary Principle for deci- sion-making in the public policy arena. Eur. J. Oncol., 9 (1), 9-12, 2004

Elsevier Science refused to publish a study of IBM workers that IBM sought to keep from public view. Occupational and environmental health (OEH) suffers from the absence of a level playing field on which science can thrive. Industry pays for a substantial portion of OEH research. Studies done by private consulting firms or academic institutions may be published if the results suit the sponsoring companies, or they may be cen-sored. OEH journals often reflect the dominance of industry influence on research in the papers they publish , sometimes withdrawing or modifying papers in line with industry and advertising agendas. Although such practices are widely recognized, no fundamental change is supported by government and industry or by professional organizations. I n 1985, a chemist working in the Material Analysis Department at the IBM research facility in San Jose, California, wrote a memo to IBM Corporate Headquarters , alerting IBM officials to a cluster of cancers that his colleagues had experienced. 1 Among the group of 12 workers in a research and development laboratory , two had died of brain cancer, two had died of lymphatic cancer, and two had died of gastrointestinal cancers. When two more developed bone tumors and the group's leader later died of brain cancer, the survivors pressed hard to bring IBM's attention to the issue. Gary Adams, the author of the memo, said the response of a staff doctor to his request that the company monitor its workers' health had been to say such a program would be a waste of time, because " workers did not get cancer from their jobs. " 2 IBM commissioned a study of brain cancer mortality among electronics workers, to be conducted by Beall and Delzell at the University of Alabama, Birmingham (UAB). 3 The UAB investigators under contract to IBM have had considerable experience in conducting industry supported research over many years. The IBM Corporate Mortality File cited in the study report recorded deaths for virtually all U.S. IBM employees from 1969 to 1995. The study was reported in 1996, more than a decade after the Adams memo was submitted to management. The study prompted the authors to state that, " Information about specific exposures in the work environment , such as EMF, ionizing radiation, or chemical agents, was not available. Some of the observed associations are difficult to interpret because exposure information pertaining to division and job groups is …