Updated assessment of occupational safety and health hazards of climate change.

Workers, particularly outdoor workers, are among the populations most disproportionately affected by climate-related hazards. However, scientific research and control actions to comprehensively address these hazards are notably absent. To assess this absence, a seven-category framework was developed in 2009 to characterize the scientific literature published from 1988-2008. Using this framework, a second assessment examined the literature published through 2014, and the current one examines literature from 2014-2021. The objectives were to present literature that updates the framework and related topics and increases awareness of the role of climate change in occupational safety and health. In general, there is substantial literature on worker hazards related to ambient temperatures, biological hazards, and extreme weather but less on air pollution, ultraviolet radiation, industrial transitions, and the built environment. There is growing literature on mental health and health equity issues related to climate change, but much more research is needed. The socioeconomic impacts of climate change also require more research. This study illustrates that workers are experiencing increased morbidity and mortality related to climate change. In all areas of climate-related worker risk, including geoengineering, research is needed on the causality and prevalence of hazards, along with surveillance to identify, and interventions for hazard prevention and control.

Characterizing risk assessments for the development of occupational exposure limits for engineered nanomaterials.

The commercialization of engineered nanomaterials (ENMs) began in the early 2000's. Since then the number of commercial products and the number of workers potentially exposed to ENMs is growing, as is the need to evaluate and manage the potential health risks. Occupational exposure limits (OELs) have been developed for some of the first generation of ENMs. These OELs have been based on risk assessments that progressed from qualitative to quantitative as nanotoxicology data became available. In this paper, that progression is characterized. It traces OEL development through the qualitative approach of general groups of ENMs based primarily on read-across with other materials to quantitative risk assessments for nanoscale particles including titanium dioxide, carbon nanotubes and nanofibers, silver nanoparticles, and cellulose nanocrystals. These represent prototypic approaches to risk assessment and OEL development for ENMs. Such substance-by-substance efforts are not practical given the insufficient data for many ENMs that are currently being used or potentially entering commerce. Consequently, categorical approaches are emerging to group and rank ENMs by hazard and potential health risk. The strengths and limitations of these approaches are described, and future derivations and research needs are discussed. Critical needs in moving forward with understanding the health effects of the numerous EMNs include more standardized and accessible quantitative data on the toxicity and physicochemical properties of ENMs.

Advancing the framework for considering the effects of climate change on worker safety and health.

In 2009, a preliminary framework for how climate change could affect worker safety and health was described. That framework was based on a literature search from 1988-2008 that supported seven categories of climate-related occupational hazards: (1) increased ambient temperature; (2) air pollution; (3) ultraviolet radiation exposure; (4) extreme weather; (5) vector-borne diseases and expanded habitats; (6) industrial transitions and emerging industries; and (7) changes in the built environment. This article reviews the published literature from 2008-2014 in each of the seven categories. Additionally, three new topics related to occupational safety and health are considered: mental health effects, economic burden, and potential worker safety and health impacts associated with the nascent field of climate intervention (geoengineering). Beyond updating the literature, this article also identifies key priorities for action to better characterize and understand how occupational safety and health may be associated with climate change events and ensure that worker health and safety issues are anticipated, recognized, evaluated, and mitigated. These key priorities include research, surveillance, risk assessment, risk management, and policy development. Strong evidence indicates that climate change will continue to present occupational safety and health hazards, and this framework may be a useful tool for preventing adverse effects to workers.

Considerations for Using Genetic and Epigenetic Information in Occupational Health Risk Assessment and Standard Setting.

Risk assessment forms the basis for both occupational health decision-making and the development of occupational exposure limits (OELs). Although genetic and epigenetic data have not been widely used in risk assessment and ultimately, standard setting, it is possible to envision such uses. A growing body of literature demonstrates that genetic and epigenetic factors condition biological responses to occupational and environmental hazards or serve as targets of them. This presentation addresses the considerations for using genetic and epigenetic information in risk assessments, provides guidance on using this information within the classic risk assessment paradigm, and describes a framework to organize thinking about such uses. The framework is a 4 × 4 matrix involving the risk assessment functions (hazard identification, dose-response modeling, exposure assessment, and risk characterization) on one axis and inherited and acquired genetic and epigenetic data on the other axis. The cells in the matrix identify how genetic and epigenetic data can be used for each risk assessment function. Generally, genetic and epigenetic data might be used as endpoints in hazard identification, as indicators of exposure, as effect modifiers in exposure assessment and dose-response modeling, as descriptors of mode of action, and to characterize toxicity pathways. Vast amounts of genetic and epigenetic data may be generated by high-throughput technologies. These data can be useful for assessing variability and reducing uncertainty in extrapolations, and they may serve as the foundation upon which identification of biological perturbations would lead to a new paradigm of toxicity pathway-based risk assessments.

The Global Landscape of Occupational Exposure Limits--Implementation of Harmonization Principles to Guide Limit Selection.

Occupational exposure limits (OELs) serve as health-based benchmarks against which measured or estimated workplace exposures can be compared. In the years since the introduction of OELs to public health practice, both developed and developing countries have established processes for deriving, setting, and using OELs to protect workers exposed to hazardous chemicals. These processes vary widely, however, and have thus resulted in a confusing international landscape for identifying and applying such limits in workplaces. The occupational hygienist will encounter significant overlap in coverage among organizations for many chemicals, while other important chemicals have OELs developed by few, if any, organizations. Where multiple organizations have published an OEL, the derived value often varies considerably-reflecting differences in both risk policy and risk assessment methodology as well as access to available pertinent data. This article explores the underlying reasons for variability in OELs, and recommends the harmonization of risk-based methods used by OEL-deriving organizations. A framework is also proposed for the identification and systematic evaluation of OEL resources, which occupational hygienists can use to support risk characterization and risk management decisions in situations where multiple potentially relevant OELs exist.

Overview of Risk Management for Engineered Nanomaterials.

Occupational exposure to engineered nanomaterials (ENMs) is considered a new and challenging occurrence. Preliminary information from laboratory studies indicates that workers exposed to some kinds of ENMs could be at risk of adverse health effects. To protect the nanomaterial workforce, a precautionary risk management approach is warranted and given the newness of ENMs and emergence of nanotechnology, a naturalistic view of risk management is useful. Employers have the primary responsibility for providing a safe and healthy workplace. This is achieved by identifying and managing risks which include recognition of hazards, assessing exposures, characterizing actual risk, and implementing measures to control those risks. Following traditional risk management models for nanomaterials is challenging because of uncertainties about the nature of hazards, issues in exposure assessment, questions about appropriate control methods, and lack of occupational exposure limits (OELs) or nano-specific regulations. In the absence of OELs specific for nanomaterials, a precautionary approach has been recommended in many countries. The precautionary approach entails minimizing exposures by using engineering controls and personal protective equipment (PPE). Generally, risk management utilizes the hierarchy of controls. Ideally, risk management for nanomaterials should be part of an enterprise-wide risk management program or system and this should include both risk control and a medical surveillance program that assesses the frequency of adverse effects among groups of workers exposed to nanomaterials. In some cases, the medical surveillance could include medical screening of individual workers to detect early signs of work-related illnesses. All medical surveillance should be used to assess the effectiveness of risk management; however, medical surveillance should be considered as a second line of defense to ensure that implemented risk management practices are effective.

A framework for the concurrent consideration of occupational hazards and obesity.

Occupational hazards and obesity can lead to extensive morbidity and mortality and put great financial burden on society. Historically, occupational hazards and obesity have been addressed as separate unrelated issues, but both are public health problems and there may be public health benefits from considering them together. This paper provides a framework for the concurrent consideration of occupational hazards and obesity. The framework consists of the following elements: (i) investigate the relationship between occupational hazards and obesity, (ii) explore the impact of occupational morbidity and mortality and obesity on workplace absence, disability, productivity and healthcare costs, (iii) assess the utility of the workplace as a venue for obesity prevention programs, (iv) promote a comprehensive approach to worker health and (v) identify and address the ethical, legal and social issues. Utilizing this framework may advance the efforts to address the major societal health problems of occupational hazards and obesity.

Single-nucleotide polymorphisms in selected cytokine genes and risk of adult glioma.

A role of immunological factors in glioma etiology is suggested by reports of an inverse relationship with history of allergy or autoimmune disease. To test whether single-nucleotide polymorphisms (SNPs) in cytokine genes were related to risk of adult glioma, we genotyped 11 SNPs in seven cytokine genes within a hospital-based study conducted by the National Cancer Institute and an independent, population-based study by the National Institute for Occupational Safety and Health (overall 756 cases and 1190 controls with blood samples). The IL4 (rs2243248, -1098T>G) and IL6 (rs1800795, -174G>C) polymorphisms were significantly associated with risk of glioma in the pooled analysis (P trend = 0.006 and 0.04, respectively), although these became attenuated after controlling for the false discovery rate (P trend = 0.07 and 0.22, respectively). Our results underscore the importance of pooled analyses in genetic association studies and suggest that SNPs in cytokine genes may influence susceptibility to glioma.

Framework for considering genetics in the workplace.

There has been aproliferation of genetic information in the last 25 years resulting in a spectrum of existing and potential uses in the workplace. These uses of have different issues and implications which may be more clearly considered in a framework that identifies three distinct uses (research, practice, and regulation/litigation) for inherited genetic factors and acquired genetic effects. Inherited genetic factors pertain to the characteristics of the genes, and acquired genetic effects to the impact on genes and chromosomes of environmental and constitutional factors. Critical in assessing the issues involving genetics in the workplace is attention on the rights of workers, validity and clinical utility of genetic information, cost pressures on employers, and societal implications. Genetic information may provide mechanistic and diagnostic insight into occupational diseases and allow for targeting high-risk groups, improving risk assessments, and providing early indicators of risk. However, these benefits are more likely to be realized and problems avoided when the different uses are considered in a framework that distinguishes them by type and content. The application of such a framework makes it easier to assess whether there is a sufficient evidence base and worker safeguards in place for any particular use of genetic information.

Taking stock of the occupational safety and health challenges of nanotechnology: 2000-2015.

Engineered nanomaterials significantly entered commerce at the beginning of the 21st century. Concerns about serious potential health effects of nanomaterials were widespread. Now, approximately 15 years later, it is worthwhile to take stock of research and efforts to protect nanomaterial workers from potential risks of adverse health effects. This article provides and examines timelines for major functional areas (toxicology, metrology, exposure assessment, engineering controls and personal protective equipment, risk assessment, risk management, medical surveillance, and epidemiology) to identify significant contributions to worker safety and health. The occupational safety and health field has responded effectively to identify gaps in knowledge and practice, but further research is warranted and is described. There is now a greater, if imperfect, understanding of the mechanisms underlying nanoparticle toxicology, hazards to workers, and appropriate controls for nanomaterials, but unified analytical standards and exposure characterization methods are still lacking. The development of control-banding and similar strategies has compensated for incomplete data on exposure and risk, but it is unknown how widely such approaches are being adopted. Although the importance of epidemiologic studies and medical surveillance is recognized, implementation has been slowed by logistical issues. Responsible development of nanotechnology requires protection of workers at all stages of the technological life cycle. In each of the functional areas assessed, progress has been made, but more is required.

Incorporating biomarkers into cancer epidemiology: a matrix of biomarker and study design categories.

During the last decade, there has been increasing interest in the use of biomarkers in cancer epidemiology to enhance exposure assessment, to gain insight into disease mechanism, and to understand acquired or inherited susceptibility. To facilitate the use of biomarkers in health research, biomarkers have been divided into categories that depict the spectrum of cancer pathogenesis from exposure to disease. In this paper, we consider the epidemiological designs most suitable for the study of each type of marker. In particular, we present a two-dimensional matrix relating the biomarker categories on one axis to four different types of activities (laboratory, transitional, and etiological studies and public health applications) that develop markers and apply them in human populations. We then use the matrix to review the potential application of biomarkers in observational studies of cancer etiology, discussing the advantages, disadvantages, and logistical considerations in using biomarkers to answer research questions.

Hemoglobin adducts and sister chromatid exchanges in hospital workers exposed to ethylene oxide: effects of glutathione S-transferase T1 and M1 genotypes.

Ethylene oxide (EtO) is a genotoxic carcinogen with widespread uses as an industrial chemical intermediate and sterilant. We examined the effects of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) genotypes on the levels of N-(2-hydroxyethyl)valine (HEV) adducts in the erythrocytes and sister chromatid exchange (SCE) in lymphocytes from a group of 58 operators of sterilizers that used EtO and nonexposed workers from nine hospitals in the United States and one hospital in Mexico City. Cumulative exposure to EtO was estimated during the 4-month period before the collection of blood samples. Results showed that EtO exposure was significantly associated with the levels of HEV adducts and SCE after adjusting for cigarette smoking and other potential confounders. A significantly higher HEV adduct level (0.17 +/- 0.03 versus 0.08 +/- 0.01, mean +/- SE; P = 0.02) but lower SCE frequency (5.31 +/- 0.39 versus 6.21 +/- 0.17; P = 0.04) was observed in subjects with homozygous deletion of the GSTT1 gene (null genotype) as compared with those with at least one copy of the gene (positive genotype). In multiple regression analysis, the GSTT1-null genotype was associated with an increase in HEV adduct level (beta = 1.62; P = 0.02) and a decrease in SCE frequency (beta = -1.25; P = 0.003) after adjusting for age, gender, race, education, cigarette smoking, and EtO exposure status. The inverse SCE-GSTT1 relationship remained unchanged when SCE was further examined in relation to HEV adducts as an indicator of the internal EtO dose. The GSTM1 genotype was not associated with the level of either HEV adduct or SCE. These data indicate that the GSTT1-null genotype is associated with increased formation of EtO-hemoglobin adducts in relation to occupational EtO exposure, suggesting that individuals with homozygous deletion of the GSTT1 gene may be more susceptible to the genotoxic effects of ETO: The unexpected finding of decreased SCEs, which is less clear, may be attributed to the nonchemical specificity of this end point and the lack of expression of the GSTT1 enzyme in lymphocytes.

Biomarkers in epidemiology: scientific issues and ethical implications.

The current generation of biologic markers have three characteristics that differentiate them from previous ones. These include the ability to detect xenobiotics at concentrations at the cellular and molecular level, to detect earlier biologic changes presumptive of disease or disease risk, and to identify a detailed continuum of events between an exposure and resultant disease. If biomarkers are to enhance cancer epidemiology, they must be valid, reliable, and practical. When these characteristics have not been previously demonstrated, pilot studies should be conducted prior to the primary study. Interdisciplinary communication and collaboration is required so that useful markers are selected and that collection and handling, assay, and interpretation are appropriate. The status of many biomarkers is that they have been developed in the laboratory but lack validation for field use. Validation of a marker for use in a population requires attention to issues of background prevalence, sample size, natural history, persistence, variability, confounding factors, and predictive value. Additionally, practical features such as subject preparation, access to specimens, specimen storage aspects, and costs must be clarified. Ultimately, the use of biologic markers in epidemiologic studies will depend on how well the markers increase ability to reduce misclassification, provide for better interpretation of exposure-disease associations, and increase opportunities for prevention. Validation studies and general research using biomarkers also have clinical, ethical, and legal implications. These range from communicating uncertainty about the meaning of a marker to the kinds of societal response that result when groups or individuals are identified as having an "abnormal" marker frequency.

Ethical considerations, confidentiality issues, rights of human subjects, and uses of monitoring data in research and regulation.

Biomarkers are potentially powerful tools for use in research and regulation. Their derivation from biologic specimens collected from human subjects does, however, present many ethical implications. Ethical issues are relevant in almost each facet of human biomarker research studies: design, identification and recruitment of subjects, handling and use of the data, and interpretation and communication of results. Researchers also face a number of dilemmas when considering the use of human biologic specimens and new biomarkers. The mere fact that such markers are the result of measurements in human specimens gives the appearance of being more accurate than traditional sources of information such as questionnaires or environmental monitoring; yet, this may not always be the case. The meaning of the results of biomarker studies may be unclear because the purpose of the study is usually for research rather than clinical purposes. There generally are no established normal ranges for biomarkers and the interpretation of findings are often difficult. Researchers may not communicate these results to subjects or consider followup action because the task may be too difficult or undefined, or the reaction of the subject cannot be anticipated. A wide range of practices in this regard exists among researchers. Many questions remain unanswered about the use of biologic specimens. These include questions of ownership and access to specimens. Related to this is the question of whether specimens collected for one research purpose can be used for an entirely different research purpose. This is still an open question.(ABSTRACT TRUNCATED AT 250 WORDS)

Approaches for assessing health risks from complex mixtures in indoor air: a panel overview.

Critical to a more definitive human health assessment of the potential health risks from exposure to complex mixtures in indoor air is the need for a more definitive clinical measure and etiology of the health effects of complex mixtures. This panel overview highlights six of the eight presentations of the conference panel discussion and features a number of the major topical areas of indoor air concern. W. G. Meggs assessed clinical research priorities with primary focus on the role of volatile organic chemicals in human health, recognizing the areas where definitive data are lacking. By recognizing many types of chemical sensitivity, it may be possible to design studies that can illuminate the mechanisms by which chemical exposure may cause disease. The critically important topic of multiple chemical sensitivity was discussed by N. A. Ashford, who identified four high risk groups and defined the demographics of these groups. P. A. Schulte addressed the issue of biological markers of susceptibility with specific considerations of both methodological and societal aspects that may be operative in the ability to detect innate or inborne differences between individuals and populations. Three case studies were reviewed. H. Anderson discussed the past and present priorities from a public health perspective, focusing on those issues dealing with exposures to environmental tobacco smoke and formaldehyde off-gassing from materials used in mobile home construction. J. J. Osborne described several case studies involving wood smoke exposure to children, with emphasis on the significantly greater occurrence of chronic respiratory symptoms and acute chest illness for children from homes heated with woodburning stoves.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethical issues in the communication of results.

The communication of the results of medical tests used in epidemiologic studies or the results of such studies involve ethical issues. These issues range from the rights of subjects to receive these results to the obligation of investigators to communicate clearly and entirely not only the results but their meaning. This can be problematic in epidemiologic studies where biological or medical monitoring yields uncertain findings. Generally, the results of epidemiologic studies are group-oriented and have limited meaning for the individual. It is incumbent on investigators to express this limitation. The investigators may also have a responsibility to alert any subject with clinical conditions that require immediate or long-term follow-up.

Scientific and ethical aspects of genetic screening of workers for cancer risk: the case of the N-acetyltransferase phenotype.

Our expanding capacity to detect human genetic susceptibility to various chronic diseases presents us with the opportunity to screen asymptomatic people for purposes of employment, insurance or credit. It also brings with it the responsibility of deciding the ethical and social value of such applications. This paper addresses scientific and ethical issues involved in the use of genetic screening techniques which intend to identify individuals that have more than average susceptibility to develop cancer from workplace chemical exposures. The case in point is the genetic polymorphism for N-acetyltransferase activity and the risk of bladder cancer in workers exposed to carcinogenic arylamines. The acetyltransferase polymorphism is related to the metabolic activation and deactivation of carcinogenic arylamines. Any genetic screening test for cancer susceptibility must be based upon sound science. For example, it must be demonstrated that a specific metabolic phenotype is a risk factor for cancer and, further, that the available tests accurately classify the subjects as to the phenotype. If there is a poor correspondence between phenotype and genotype, or a large intra-individual variability in phenotype, misclassification may result. Also, bias, arising as a consequence of enzyme induction by specific substrates, must be ruled out. Genetic screening of workers for susceptibility to cancer seems to us an ethically unacceptable and premature, application of the science.(ABSTRACT TRUNCATED AT 250 WORDS)

Using molecular epidemiology in assessing exposure for risk assessment.

Quantitative estimation of health risks depends on exposure characterization, the nature of the dose response relationships, and the toxicity of the agents involved. The greatest uncertainties in risk assessment almost always arise from sparse or inadequate exposure data, inadequate understanding of exposure mechanisms, and insufficient understanding of the exposure-dose-response pathway. Additional sources of uncertainty arise when mixed or multiple exposures are implicated in the disease pathway, and as a result of variability in both exposures and responses within and between individuals. Here we consider the role of exposure assessment in the risk assessment process, the use of biological markers or molecular epidemiology to contribute to improvements in exposure assessment for risk assessment, and uncertainties associated with the use of biological markers.

p53 mutations in human bladder cancer.

Mutations in the tumor suppressor gene p53 play an important role in carcinogenesis and tumor progression. To assess the status of p53 from genomic DNA from bladder cancer samples a two stage polymerase chain reaction was employed. The technique provided material for subsequent detection of mutations by Single Strand Conformation Polymorphism (SSCP) analysis followed by DNA sequence analysis. SSCP analysis of exons 5 to 9 of p53 was performed using fragments from PCR end-labeled with 32P followed by autoradiography using an electrophoresis system with temperature control. This SSCP method improved resolution of mutations in exons 5, 7, and 8 and the sharpness of bands in exons 6 and 9. Bands with altered migration patterns were excised from the dried SSCP gels, reamplified by PCR, and sequenced. Mutations in conserved exons 5, 6, 7, 8, and 9 of the p53 gene were analyzed from bladder tumor biopsies. Our results are consistent with the literature in that mutations in p53 are predominantly found in high grade bladder cancer (Odds Ratio = 4.05, Fisher Exact P = 0.104); however, the results were not statistically significant due to small numbers. Eight of 35 (23%) tumor samples examined showed mutations in p53 (including two double mutations). Six of 13 (46%) grade III and IV tumors had p53 mutations vs. 2 of 17 (12%) grade I and II tumors. Normal individuals carried no p53 mutations. We found no correlation between pack years of smoking and mutation in p53. The spectrum of mutations confirmed a high proportion of G:C C:G transversions as well as the occurrence of double mutations.