Occupational exposure to genotoxic agents.

Millions of workers in the United States are potentially exposed each year to hazardous chemicals, dusts, or fibers in occupational settings. Some of these agents are genotoxic and may cause genetic alterations in the somatic or germ cells of exposed workers. Such alterations, if they occur in proto-oncogenes or tumor suppressor genes, which are involved in controlling cell growth or differentiation, may lead to the development of cancer. Genetic alterations in germ cells may also lead to reproductive failure or genetic disorders in subsequent generations. It has been estimated that occupational exposure accounts for 4% of all human cancers and up to 30% of cancer among blue-collar workers. Approximately 20,000 cancer deaths each year are attributable to occupational exposure in the United States. Occupational cancer and reproductive abnormalities have been listed on the National Occupational Research Agenda master list of research priorities as major occupational diseases and injuries.     

A Review of the Use of Pictograms for Communicating Pesticide Hazards and Safety Instructions: Implications for EU Policy

The literature was reviewed to assess the understanding and interpretation of pictograms used in pesticide exposure risk communication, and to assess the results in the context of the new European Union (EU) regulatory context for the sustainable use of pesticides. The results indicate that the understanding of pictograms used on pesticide labels by workers and operators is generally low. Standardized approaches, contrary to their claims, are not easily understandable, culturally neutral, or universally understood. Although there is scope for the greater use of pictograms in training, it is important to stress that they should never replace the full and frequent verbal training in a language understood by the trainee. They can, however, be used to complement training, facilitate recall, and encourage compliance. While the policy affecting the handling, labeling, and use of pesticides is applied across the EU, there has been no analysis of the different types of pictograms that have been used in the European context, nor the different ways that they are employed (e.g., on labels, on signs, during training), nor understanding of their meaning by European workers and operators. Furthermore, the implications for risk with residents and bystanders are less clear than for workers and operators.     

Man-made mineral (vitreous) fibres: evaluations of cancer hazards by the IARC Monographs Programme

Man-made vitreous (glass-like) fibres are non-crystalline, fibrous inorganic substances (silicates) made primarily from rock, slag, glass or other processed minerals. These materials, also called man-made mineral fibres, include glass fibres (used in glass wool and continuous glass filament), rock or stone wool, slag wool and refractory ceramic fibres. They are widely used for thermal and acoustical insulation and to a lesser extent for other purposes. These products are potentially hazardous to human health because they release airborne respirable fibres during their production, use and removal. Man-made mineral fibres and man-made vitreous fibres have been the subject of reviews by IARC Monographs Working Groups in 1987 and 2001, respectively, which resulted in evaluations of the carcinogenic hazard to humans from exposure to these materials. These reviews and evaluations have been published as Volumes 43 and 81 of the IARC Monographs series [IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 43, Man-made Mineral Fibres and Radon (1988); IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol. 81, Man-made Vitreous Fibres (2002)]. The re-evaluation in 2001 was undertaken because there have been substantial improvements in the quality of the epidemiological information available on the carcinogenicity to humans of glass fibres, continuous glass filament and rock/slag wool. The new evaluations have addressed the limitations of earlier cohort studies, particularly concerning the lack of adjustment with respect to concomitant risk factors such as smoking and other sources of occupational exposure. In addition, the evaluation of the evidence for carcinogenicity of glass fibres to experimental animals has been refined, by making a distinction between insulation glass wool and special-purpose glass fibres. The results of the evaluations in 1987 and 2001 are thus different in several aspects. In this paper, the reviews and evaluations of the carcinogenic hazards of exposure to man-made mineral fibres (MMMF, Monograph volume 43, [1]) and man-made vitreous fibres (MMVF, Monograph volume 81, [2]) are summarised, and the differences explained. In particular, the considerations of the respective IARC Monographs Working Groups (1987, 2001) in reaching their conclusions are discussed in some detail.     

Benchmark Dose Profiles for Joint‐Action Quantal Data in Quantitative Risk Assessment

Summary Benchmark analysis is a widely used tool in public health risk analysis. Therein, estimation of minimum exposure levels, called Benchmark Doses (BMDs), that induce a prespecified Benchmark Response (BMR) is well understood for the case of an adverse response to a single stimulus. For cases where two agents are studied in tandem, however, the benchmark approach is far less developed. This article demonstrates how the benchmark modeling paradigm can be expanded from the single‐dose setting to joint‐action, two‐agent studies. Focus is on response outcomes expressed as proportions. Extending the single‐exposure setting, representations of risk are based on a joint‐action dose–response model involving both agents. Based on such a model, the concept of a benchmark profile (BMP) – a two‐dimensional analog of the single‐dose BMD at which both agents achieve the specified BMR – is defined for use in quantitative risk characterization and assessment. The resulting, joint, low‐dose guidelines can improve public health planning and risk regulation when dealing with low‐level exposures to combinations of hazardous agents.     

Legislative aspects: an evaluation of the impact of COSHH schedule 9 for assessing biological risks

Exposure to biological agents in the workplace can cause infection, allergy or toxicosis. Health effects caused by biological agents in the workplace are related both to incidental exposure and to deliberate work with microorganisms. A small but significant percentage of occupational allergy is associated with biological agents in organic dusts, and a new reporting scheme recorded more than 1000 new cases of occupational infection in its first year. Assessing risks from workplace biological agents in the UK forms part of the Control of Substances Hazardous to Health (COSHH) regulations. Legislation (Schedule 9) and guidance which deals with biological agents were added to implement EC Biological Agents Directives and to emphasise the position of biological agents in COSHH.We evaluated the impact of COSHH Schedule 9 by interviewing representatives of workers in laboratories deliberately handling microorganisms and discussing in a Focus Group format with representatives from industries where incidental exposure to microorganisms could occur. This paper describes the outcome of that evaluation and examines the tools available to assess risks from exposure to workplace microorganisms.     

EU biotech crop regulations and environmental risk: a case of the emperor's new clothes?

European Union Commissioner for the Environment Stavros Dimas recently hailed 'upgraded' non-genetically modified (GM) crops as an alternative to GM crops. A comparative analysis of the environmental risks associated with such non-GM herbicide-resistant crops and GM herbicide-resistant crops is presented here. The analysis highlights serious weaknesses in the European Union (EU) regulatory framework, and the contradictory policy of the EU Commission on the precautionary principle is also shown. The continued political stance of ignoring these regulatory and policy inconsistencies is examined and found to be flawed. It is postulated that, even in the face of these flaws and coupled with recent statements from the UK drawing attention to inconsistencies in the EU regulatory framework, the EU will continue to ignore the real and present environmental risks associated with upgraded non-GM crops for biopolitical reasons.     

Risk of occupationally acquired illnesses from biological threat agents in unvaccinated laboratory workers

Many vaccines for bioterrorism agents are investigational and therefore not available (outside of research protocol use) to all at-risk laboratory workers who have begun working with these agents as a result of increased interest in biodefense research. Illness surveillance data archived from the U.S. offensive biological warfare program (from 1943 to 1969) were reviewed to assess the impact of safety measures on disease prevention (including biosafety cabinets [BSCs]) before and after vaccine availability. Most laboratory-acquired infections from agents with higher infective doses (e.g., anthrax, glanders, and plague) were prevented with personal protective measures and safety training alone. Safety measures (including BSCs) without vaccination failed to sufficiently prevent illness from agents with lower infective doses in this high-risk research setting. Infections continued with tularemia (average 15/year), Venezuelan equine encephalitis (1.9/year), and Q fever (3.4/year) but decreased dramatically once vaccinations became available (average of 1, 0.6, and 0 infections per year, respectively). While laboratory-acquired infections are not expected to occur frequently in the current lower-risk biodefense research setting because of further improvements in biosafety equipment and changes in biosafety policies, the data help to define the inherent risks of working with the specific agents of bioterrorism. The data support the idea that research with these agents should be restricted to laboratories with experience in handling highly hazardous agents and where appropriate safety training and precautions can be implemented.     

European Directives for Air Quality: Analysis of the New Limits in Comparison with Asthmatic Symptoms in Children Living in the Oporto Metropolitan Area,Portugal

This study analyzes the air pollutant concentrations in the Oporto Metropolitan Area, Portugal, comparing them with the limits fixed by the previous legislation currently in force, as well as by European Union (EU) Directives. The impacts were estimated using the prevalence of asthmatic symptoms and asthma in children as indicators. The objectives were: (i) to evaluate the impact on air quality associated with the reduction of sulphur content in fuels, (ii) to compare health impacts associated with SO₂ and particles with the limits fixed by both legislations, and (iii) to assess whether the delayed application of the EU Directives can be associated with health risks. It was concluded that: (i) after the reduction of sulphur content in fuels, a reduction of 60% of the annual averages of SO₂ concentration was observed, as well as a decrease in the rates of asthmatic symptoms and asthma in children, (ii) the limits fixed by the previous legislation do not protect against health impacts of SO₂ and particles, but the new EU Directives are protective; the EU limits for PM₁₀ are very difficult to attain, being probably unnecessarily low concerning the impact on asthmatic symptoms and asthma in children, and (iii) the delayed application of the EU Directives can be associated with unnecessary health risks.     

Scientific basis for uncertainty factors used to establish occupational exposure limits for pharmaceutical active ingredients

The traditional “safety factor”; method has been used for years to establish occupational exposure limits (OELs) for active ingredients used in drugs. In the past, a single safety factor was used to address all sources of uncertainty in the limit setting process. The traditional 100‐fold safety factor commonly used to derive an acceptable daily intake value incorporates a default factor of 10 each to account for interindividual variability and interspecies extrapolation. Use of these defaults can lead to overly conservative health‐based limits, especially when they are combined with other (up to 10‐fold) factors to adjust for inadequacies in the available database. In recent years, attempts have been made to quantitate individual sources of uncertainty and variability to improve the scientific basis for OELs. In this paper we discuss the science supporting reductions in the traditional default uncertainty factors. A number of workplace‐specific factors also support reductions in these factors. Recently proposed alternative methodologies provide a framework to make maximum use of preclinical and clinical information, e.g., toxicokinetic and toxicodynamic data, to reduce uncertainties when establishing OELs for pharmaceutical active ingredients.     

Is there a health hazard for building occupants of airborne mineral fibers exposure?

Summary Asbestos containing material (ACM) inside buildings is an important concern for the health of their occupants. In France, for the assessment of airborne asbestos concentrations inside building, we use the indirect TEM measurement method constantly improved from 1978 on. By contrast, in the U.S.A. and UK the direct method is used. We have carried out a study in order to compare mass and numerical concentration fibres from the same samples, the tendency being now to express the results in fibre/litre. Concerning asbestos fibres released from man made mineral fibres (MMMF), optical microscope is used and results are expressed in numerical concentrations. Epidemiological studies of different occupational cohorts suggest that amphibole fibres present a greater health risk than chrysotile. Concerning indoor pollution by mineral wool, the health hazard seems negligible. The appraisal of this public health problem remains to be done. In France, a multidisciplinary study group has been created to provide advices related to corrective actions. Information on this public health problem is expected from the epidemiologic longitudinal survey, still in progress, of a cohort of workers, exposed to ACM in Paris university buildings.     

Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways

The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC) report Toxicity Testing in the 21(st) Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a) "toxicity pathways" (the innate cellular pathways that may be perturbed by chemicals) and (b) the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU). EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair.     

Toxicity Testing in the 21st Century: Defining New Risk Assessment Approaches Based on Perturbation of Intracellular Toxicity Pathways

The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC) report Toxicity Testing in the 21^st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a) “toxicity pathways” (the innate cellular pathways that may be perturbed by chemicals) and (b) the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU). EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair.     

Evaluation of the Influence of Magnetic Field on Female Users of an Induction Hob in Ergonomically Sound Exposure Situations

The hypothesis being tested was that the exposure of female workers to the electromagnetic field (EMF) emitted by an induction hob (IHb) meeting public exposure limitations (evaluated according to EN/IEC 62233) is also compliant with European Directive 2013/35/EU on workers’ protection. The electric field induced in three female models in a realistic ergonomically comfortable posture near IHb was evaluated using numerical models of 25 kHz EMF sources (IHb covered by cooking vessels). It was found that, in analyzed ergonomically comfortable exposure situations, the electric field induced in the user's body may exceed public and workers’ limits when the vessels do not match the dimensions of IHb's heating zone. This can even be the case when IHb complies with Conformité Européenne labeling requirements (i.e. EMF exposure falls below public limits 30 cm away from IHb edge). In the 36 exposure scenarios analyzed, statistically significant differences were found when the distances from IHb and vessel dimension, and the height and body mass index of models in exposure scenarios varied, but not between the use of models of pregnant and nonpregnant women. The use of IHb complying with European requirements on general public protection does not ensure that EMF exposure to workers complies with the relevant limits. Adequate protection measures need to address these occupational environmental hazards. © 2020 Bioelectromagnetics Society.     

Temporary derogation from European environmental legislation for clinical trials of genetically modified organisms for coronavirus disease 2019

Attempts to streamline environmental procedures for those products containing or consisting of genetically modified organisms (GMOs) among the European Union (EU) Member States are ongoing but still need to be further developed. These procedures can be complex, resource-intensive and time-consuming. Some candidate vaccines currently under development for COVID-19 include genetically modified viruses, which may be considered GMOs. Given the public health emergency caused by the COVID-19 outbreak, on July 15, 2020, the European Parliament approved a temporary derogation of the European environmental requirements to facilitate that those clinical trials with GMOs intended to treat or prevent COVID-19 can start as soon as possible in Europe. This measure has been very controversial, since it could entail risks to human health and the environment, and could be seen as unfair for other products targeting unmet medical needs. With the adoption of this measure, the bottlenecks and obstacles for the development of innovative GMO-based medicines in the EU that the environmental legislation entails have become even more evident.     

Chelation therapy in workers with lead exposure.

Occupational lead overexposure remains a major problem. To evaluate the settings in which physicians appropriately prescribe chelation therapy for lead exposure, 7 cases were identified from physician phone calls and mandatory laboratory reporting of elevated blood lead levels to the California Department of Health Services. In the 2 workers with the highest blood lead levels (both of whom had severe symptoms), treatment was indicated. Physicians inappropriately prescribed chelating agents to workers with ongoing lead exposure as prophylaxis against rising blood lead levels and to treat atherosclerotic heart disease. Workers'' personal physicians identified lead overexposure in 5 of the 7 cases. Workplace lead medical surveillance programs mandated by the federal Occupational Safety and Health Administration were inadequate in all 5 of the workplaces where information was available.     

Consideration of Background Radiation in Ecological Risk Assessments

Background or ambient concentrations are often considered in the evaluation of potential risks to ecological receptors from exposure to hazardous chemicals in the environment. Such an evaluation may be a component of the screening or final risk management process and sets the baseline from which risks contributed by site-related activities can be addressed. Although the process for the evaluation of potential radiological risks to ecological receptors is less formalized than the chemical hazard assessment process, background remains an issue that should be addressed when considering potential site-related impacts. This paper briefly presents the ecological risk assessment approaches used to address background radionuclide concentrations at three United States Department of Defense Facilities. The concepts of total radiation dose, and tolerance and adaptation of populations to radiation are also discussed within the context of background radiation.     

Multidisciplinary European Low Dose Initiative (MELODI): strategic research agenda for low dose radiation risk research

MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website (http://www.melodi-online.eu/sra.html).     

Probabilistic Environmental Risk Assessment for Dibutylphthalate (DBP)

In the risk assessment methods for new and existing chemicals in the European Union (EU), environmental “risk” is characterized by the deterministic quotient of exposure and effects (PEC/PNEC). From a scientific viewpoint, the uncertainty in the risk quotient should be accounted for explicitly in the decision making, which can be done in a probabilistic risk framework. To demonstrate the feasibility and benefits of such a framework, a sample risk assessment for an existing chemical (dibutylphthalate, DBP) is presented in this paper. The example shows a probabilistic framework to be feasible with relatively little extra effort; such a framework also provides more relevant information. The deterministic risk quotients turned out to be worst cases at generally higher than the 95th percentile of the probability distributions. Sensitivity analysis proves to be a powerful tool in identifying the main sources of uncertainty and thus will be effective for efficient further testing. The distributions assigned to the assess ment factors (derivation of the PNEC) dominate the total uncertainty in the risk assessment; uncertainties in the release estimates come second. Large uncertainties are an inherent part of risk assessment that we have to deal with quantitatively. However, the most appropriate way to characterise effects and risks requires further attention. Recommendations for further study are identified.     

Pesticide Risk Perceptions,Knowledge, and Attitudes of Operators,Workers, and Residents: A Review of the Literature

The literature on the risk perceptions, knowledge levels, and attitudes of operators, workers, and residents in relation to non-dietary exposure to agricultural pesticides is reviewed. No literature was identified in relation to bystander exposure. Research has primarily been conducted on participants in developing countries and migrant workers in the United States. For operators and workers, illiteracy, poverty, and a perception that exposure to pesticides is an inevitable part of their work results in limited adoption of safety precautions while using and storing pesticides. As a result, risk communication activities aimed at operator and workers need to take account of the wider socioeconomic and cultural conditions in which workers and operators are working and living. There is less research focused on residents’ and bystanders’ perceptions, attitudes, and behaviors. The lack of European data in general, and residents’ and bystanders’ data in particular, represents a knowledge gap that is pertinent to emerging EU legislation requiring residents’ and bystanders’ inclusion in pesticide risk assessment. This review provides a comprehensive overview that can assist policy-makers, and risk communicators in the development of targeted training and awareness-raising material for operators, workers, bystanders, and residents. Areas for future research are suggested.     

Historical review of occupational exposures and cancer risks in medical radiation workers

Epidemiological studies of medical radiation workers have found excess risks of leukemia, skin and female breast cancer in those employed before 1950 but little consistent evidence of cancer risk increases subsequently. Occupational radiation-related dose-response data and recent and lifetime cancer risk data are limited for radiologists and radiologic technologists and lacking for physicians and technologists performing fluoroscopically guided procedures. Survey data demonstrate that occupational doses to radiologists and radiologic technologists have declined over time. Eighty mostly small studies of cardiologists and fewer studies of other physicians reveal that effective doses to physicians per interventional procedure vary by more than an order of magnitude. For medical radiation workers, there is an urgent need to expand the limited information on average annual, time-trend and organ doses from occupational radiation exposures and to assess lifetime cancer risks of these workers. For physicians and technologists performing interventional procedures, more information about occupational doses should be collected and long-term follow-up studies of cancer and other serious disease risks should be initiated. Such studies will help optimize standardized protocols for radiologic procedures, determine whether current radiation protection measures for medical radiation workers are adequate, provide guidance on cancer screening needs, and yield valuable insights on cancer risks associated with chronic radiation exposure.