2-乙氧基乙醇毒理学及卫生标准研究进展

职业流行病学调查和动物毒理学实验表明,２－乙氧基乙醇（ＥＥ）可引起生殖发育毒性、血液毒性和神经毒性。其毒代动力学特征表现为经呼吸道、皮肝同时吸收,且以后者为主,半衰期较长。ＥＥ的主要代谢产物为２－乙氧基乙酸（ＥＡＡ）,是导致生殖／发育毒笥的最终物质。ＥＥ的化学结构与甘氨酸类似,可选择性地竞争一碳单位合成,干扰了代谢旺盛的细胞组织系统,如性腺、血液、骨髓和神经等。本综述为我国开展安全性评价及健康危险     

Occupational toxicology and the control of exposure to pharmaceutical agents at work

BACKGROUND: The pharmaceutical industry employs >350 000 people worldwide in operations including research and development (R&D), manufacturing, sales and marketing. Workers employed in R&D and manufacturing sectors are potentially exposed to drug substances in the workplace that are designed to modify physiology and also to chemical precursors that are potentially hazardous to health. Pharmaceutical workers are at risk from adverse health effects, including occupational asthma, pharmacological effects, adverse reproductive outcomes and dermatitis. AIM: This study aimed to describe the approaches taken by pharmaceutical companies for identifying and communicating potential adverse health effects that may result from workplace exposures and in setting 'in-house' exposure control limits and to highlight the challenges in controlling workplace exposures to increasingly potent compounds. METHOD: The literature was reviewed by searching the Medline and HSELine databases. RESULTS: The findings are presented in five sections, covering: test methods and approaches to occupational toxicology; hazard communication; approaches to setting health-based occupational exposure limits for pharmaceutically active agents; recent approaches to risk control; and occupational hygiene and exposure controls. CONCLUSION: Significant efforts have been directed at predicting and evaluating potential occupational health hazards in the pharmaceutical industry. The pharmaceutical industry has provided leadership in controlling exposure to hazardous substances. Much of this work has been driven by a real need to control occupational exposures to substances that can have profound adverse health effects in exposed employees and that are becoming increasingly more potent.     

Graduate education in occupational hygiene: a rational framework

Occupational hygiene has been an important part of occupational health since it first emerged after World War II as the science and art that deals with the anticipation, recognition, evaluation and control of human exposures to hazards in the working environment. A need exists for well-qualified professionals who can not only respond to hazards that are currently known and understood, but also to ones that are not yet known or understood. For this, graduate-level academic programs in occupational hygiene must go beyond the training of skills and imparting of facts. Rather they must provide the education that enables the development of critical faculties, allowing future self-learning and the study of new scenarios not yet anticipated. Ideally, occupational hygiene should be taught firstly in the interdisciplinary context of the whole of occupational health (including occupational medicine, occupational health nursing, occupational safety and ergonomics) and secondly in relation to the wider field of public health (including epidemiology and biostatistics). In addition, modern occupational hygiene education also needs to embrace the management and social sciences. The Education and Research Centers (ERCs) sponsored in the United States by the National Institute of Occupational Health (NIOSH) have refined this approach and provided a useful model for all occupational hygiene education, identifying the need for both masters and doctoral-level endeavor. Other countries might usefully consider integrating existing academic programs in order to emulate the NIOSH approach, perhaps through internal and external partnerships. In terms of content, such education needs to be carried out within a framework that places human exposure to hazardous agents at the center of the anticipation-recognition-evaluation-control rationale. Such a framework also places occupational hygiene in the context of the other occupational and environmental health disciplines. Finally it has to be acknowledged that occupational hygiene is (indeed always was) a changing field. Academic programs need to be responsive to such changes, and the range of responses must include not only curricular modifications but also changes in the way that the education itself is delivered. The internet provides interesting new opportunities for distance learning that appear to have the potential not only to be efficient and convenient in terms of time and resources but also to be valid in terms of meeting the desired educational objectives.     

The hygiene and toxicology of fertilizers at the present stage

The paper touches upon the topical aspects of the hygiene and toxicology of fertilizers and their state sanitary-and-epidemiological examination at the present stage. It also considers guidelines for the toxicological-and-hygienic evaluation when state trials are carried out.     

Commentary: the role of toxicology in prevention and precaution

Advocates of the Precautionary Principle have recently called for a "new science" to support the goals of precaution-based environmental and occupational health policy. While much attention has been given to epidemiology, the evidentiary science most relevant to precaution, or prevention, is toxicology. Opportunities for enhancing the role of toxicology in public policy must consider current biases in the field. Thus, rather than a "new science", advocates for change should focus upon ensuring that current scientific methods are appropriate and that interpretations of scientific data are accurate.     

多色荧光原位杂交及其在遗传毒理学中的应用

多色荧光原位杂交 (MFISH)在检测核酸序列、染色体和基因方面有着强大功能。由于染色体结构和数目畸变被认为是遗传毒性研究重要的生物学终点 ,而该方法可准确直观地评价暴露于职业、医疗和环境毒物后的染色体异常 ,因此以其为基础的各类方法在人类遗传学、生殖医学、尤其是遗传毒理学中将会得到广泛的应用。     

What are the prospects of metal toxicology studies?

Although we still have to be careful about situations where there is still a risk of high levels of absorption of the most commonly known metals or where there is exposure to rare metals but with known toxicity, in the current transition phase from macro- to micro-doses of industrial toxics and metals in particular, it seems appropriate to encourage the development of study criteria and methods for this special field of occupational medicine. A number of aspects of the analytical techniques (ICP MS, in vivo measurements) are therefore discussed which should make for a better evaluation of doses; reference values for toxic metals intended as indispensable terms of evaluation of abnormal exposure to be related with any response by the human organism; identification and quantification of certain early effects that are of significant theoretical and practical interest, such as effects on the functional reserve and immunotoxic effects. Occupational medicine should take renewed interest in toxicological problems which, in the authors' view, have wrongly been considered outdated by the evolution of work-related diseases. On the contrary, this evolution calls for fresh and more in-depth interest also in occupational toxicology research.     

Occupational hygiene science and its application in occupational health policy, at home and abroad.

This paper examines the role of occupational hygiene in the overall framework of occupational health. It draws attention to the unique combination of required individual science subjects, and to the way in which occupational hygiene science contributes to the practice of occupational hygiene in the real world. It focuses in particular on occupational exposure standards. The paper provides, as an example, the specific case of occupational aerosol exposures. It is here that scientific research has made a notable impact on standards and led to a considerable degree of international harmonization. Finally, some broader insights into occupational exposure standards are given, based on experience gained during visits to a number of contrasting countries. The similarities and differences between the various national approaches help indicate what is generic in how standards are set. Such insights provide a basis for further international harmonization in the future. It is concluded that occupational exposure standards appear to be most effectively applied in countries where there are strong occupational hygiene cultures.     

Biological monitoring of exposure: trends and key developments

The concept of biological monitoring (BM) has gained the special interest of individual scientists and international organizations. Today, when analytical problems have almost ceased due to new laboratory techniques and quality assurance systems, the methods for interpretation of results have become the most important issue. There are important discrepancies regarding the role of biological monitoring of occupational exposure between Europe and the United States. BM has been an important tool of medical health surveillance in the European countries. In the United States it belongs rather to the field of occupational hygiene. It seems that both the approaches can be accepted. More attention should be paid to the development of the truly health-based biomarkers of exposure based on the dose-effect and dose-response relationships. New areas of application of BM of occupational exposure include determination of DNA and protein adducts, unchanged volatile organic compounds in urine, monitoring of exposure to pesticides, antineoplastic drugs, hard metals, and polycyclic aromatic hydrocarbons. In the general environment BM is the most valuable tool for acquiring knowledge of current levels of internal exposure to xenobiotics, identifying the hot spots and developments in trends of exposure. BM can provide policy makers with more accurate information on the control measures undertaken. At present, the main areas include heavy metals, persistent organic pollutants and pesticides. BM of chemical exposure has become increasingly important in the assessment of the health risk in occupational and environmental medicine. Therefore it would be worthwhile to include BM in the curricula for the training of occupational hygienists.     

Principal component analysis is a powerful instrument in occupational hygiene inquiries

Several investigators have successfully used principal component analysis (PCA) in interpreting occupational hygiene data. However, traditional textbooks in occupational hygiene provide no guidance for the application and interpretation of PCA. In this article I briefly review the basics of PCA (for those not statistically inclined), provide some guidelines for performing PCA (and designing studies that use the power of PCA), illustrate its application in understanding exposure to mixtures and the characterization of 'peak exposure', and highlight other benefits that occupational hygienists stand to gain by including PCA in their 'statistical toolkit'. I hope that this article will promote greater use and understanding of a data analysis approach that has long been helping investigators outside the field of occupational hygiene to unravel the structure behind the complex relationships among multiple correlated variables.     

Standard setting in occupational health: "philosophical" issues

This paper discusses various "philosophical" issues in standard setting in occupational and environmental health, i.e., general principles, actual procedures for standard setting, inter- and intra-agency discrepancies in procedures and criteria, and choices and decisions in the preparation of criteria documents and in the evaluation of the toxicology databases. Unpublished, possibly confidential information should be made available to expert committees, workers, and the general public. There is an urgent need to improve the validity of the toxicology databases that have to underpin occupational and environmental exposure limits. Standard setting requires various ethically loaded choices and decisions by experts, employees, managers, government officials, and politicians.     

Occupational and environmental hygiene assessment of fumigations with methyl bromide

Use of methyl bromide for pest control fumigation may result in adverse exposure to three populations: the actual fumigators; other workers not actually involved in the fumigation; and the general public in the vicinity. The risk of exposure of these three target populations in Switzerland was investigated. The methodology was a combination of occupational hygiene surveys, including a preliminary hazard analysis, with a comprehensive assessment of the safety and health systems in use based on the 'Management Oversight and Risk Tree' (MORT) method [Knox and Eicher, MORT User's Manual, Revision 2. DOE 76-45/4 (1983)]. The target populations most concerned depend on the type of fumigation. Fumigators risk severe accidental exposure although they usually wear personal protection devices. In soil and chamber fumigation, workers not involved in the fumigation may undergo high exposure (75-100 pm for 1 h), far greater than the usual time-weighted average and short-term occupational exposure limits (5-20 ppm range). Occupants of premises adjoining the fumigated buildings may also be exposed to significant concentrations (25-50 ppm for 0.1-2 h). Problems originate mainly from a lack of management controls, failure to apply an appropriate code of practice and the use of personnel who are not properly qualified and trained.     

Occupational and environmental medicine: moving the factory fence or hedging our bets?

Occupational and environmental medicine evolved out of concern for the effect of work hazards on health. The experienced gained in considering such hazards has been extended to understanding general risks in the environment. As we look toward the future, classical occupational and environmental hazards such as over exposure to lead, asbestos and mercury are waning and being replaced by concerns around sustainable development, toxicology testing and exposure information for high production volume chemicals, development of better approaches for setting workplace and community exposure limits, environmental justice and many others. The opportunities for the future exist in overcoming these new challenges.     

Validity of biological tests in epidemiological toxicology

Summary The authors emphasize the need to introduce the concept of validity (sensitivity and specificity) of biological test methods in epidemiological toxicology (occupational and public health). Up till now too often relevant information is lost, because the frequency distribution of individual data is not taken into account. The method of calculating parameters of validity is demonstrated. These parameters add relevant information for determining the feasibility of test methods; they provide valuable information not presented by classical statistical treatment of data. Several examples have been worked out to elucidate the approach.Professor in public health, particularly in regard to occupational medicine and environmental health, Faculty of Medicine, University of Amsterdam.Research worker Coronel Laboratory.     

Evolution of industrial toxicology toward vanishing doses and the human genome

BACKGROUND: This article aims to discuss the influence that the application of the recent discoveries in genomics will have on the theory and practice of industrial toxicology in developed post-industrial countries. It is stressed that the recent advances in toxicogenomics can be integrated into the existing wealth of knowledge on the toxic properties of industrial chemicals to improve the efficacy of prevention of toxicological risk. METHODS AND RESULTS: The understanding of the biochemical and physiological mechanisms underlying susceptibility or resistance to the toxic effects of industrial xenobiotics, and in particular to carcinogens, allows us to split the epidemiologically derived relationship linking the frequency of disease in the exposed population to the level of workplace contamination into a set of sequential sub-relationships linking: a) the exposure level to that of workplace contamination; b) the internal dose to the exposure level; c) the biological effect (e.g., measured through biochemical markers of early effect) to the internal dose; d) the frequency of disease to that of observation of early biochemical effects. Each of the cited relationships is affected by a degree of uncertainty due to the variability of biological response among the examined individuals, which in turn requires a definition of the statistical limits for the association functions between the variables. As a consequence, the possibility of investigating the individual biochemical and physiological steps in the causal mechanism that links toxic exposure to disease does not necessarily lead to an increase in the information potential of biological monitoring, since the uncertainty due to inter-individual variability is amplified through the sequence of causal relationships to the point that the data from biological monitoring become valueless with regard to the prediction of the frequency or probability of disease. This is particularly true when exposure to 'low doses' is investigated, as is now increasingly frequent in post-industrial developed countries, where workplace contamination is now greatly reduced to levels which may be borderline with those in the general environment. Thus at the low-dose end of the range of contamination and exposure values there is an area where, for statistical reasons consequent to the heterogeneity of examined populations, a quantitative prediction of internal exposure due to environmental contamination, of biological adverse effects due to exposure levels and of frequency of disease due to the extent or frequency of biological effects is no longer reliably possible. This in turn impairs the preventive efficacy of biological monitoring. CONCLUSIONS: A closer integration between industrial toxicology and state-of-the-art molecular genetics derived from the recent sequencing of the human genome is the way to overcome the limitations described. In particular, the individual subjects in the examined populations can be classified with regard to some genetically controlled characters relevant to the biotransformation of xenobiotics and to DNA repair and the statistical analysis of data can be performed on more homogeneous subpopulations, in order to decrease inter-individual variability of biochemical and physiological response. This in turn increases the predictive power of the biological markers, both of dose and effect, and improves the efficacy of prevention, e.g., by highlighting oversensitive subpopulations or lifestyles which can increase the risk of occupational and environmental disease.     

生物芯片分析技术在环境毒理学与环境流行病学研究中的应用

目的生物芯片分析作为新兴的现代毒理学研究技术之一,弥补和克服了传统毒理学的不足,可以快速、高通量地对毒物暴露信息进行处理,并根据毒物暴露信息的差异性分析筛选毒物作用敏感靶目标。生物芯片包括基因芯片、蛋白质芯片、细胞芯片和组织芯片,它们被广泛地应用于生命科学研究及其实践的各个领域。生物芯片的飞速发展推动了环境污染物快速评价技术的发展,改变了传统的环境流行病学评估模式。本文通过分析生物芯片在基因组学、蛋白组学、细胞学及组织分析中的原理及应用,探讨它们在环境毒理学与环境流行病学研究中存在的问题及研究展望。     

Overview and characteristics of some occupational exposures and health risks on offshore oil and gas installations

This review considers the nature, and recognition and control, of health risks in the offshore oil and gas industry from the occupational hygiene point of view. Particular attention is given to the changes in the nature of exposure and control of inhalation risks from substances hazardous to health in the UK sector, but other risks (e.g. dermatitis, noise and vibration) are also considered. The amount of published information on exposure to these hazards in the sector, or indeed on long-term health outcomes of working offshore, is limited. The approach taken to occupational health and hygiene in the sector has to be set in the context of the challenge of working in a remote and hostile environment where attention to safety and the need for emergency response to acute, rather than chronic, medical events are vital. However, changes in attitudes towards occupational health in the sector, legislation, the impact of environmental protection requirements and technology have all contributed to increasing the attention given to assessment and control of chemical and physical hazards. The health risks and benefits associated with the abandonment of installations, the application of new technologies, recovery of oil from ever deeper waters, lower staffing levels, environmental changes, the ageing workforce and the recognition of exposure patterns needing further attention/control (sequential multiple exposures, smaller workforce, peak/short-term exposures, etc.) are other current and future occupational hygiene challenges.     

Implications of gender differences for human health risk assessment and toxicology

This paper from The Human Health working group of SGOMSEC 16 examines a broad range of issues on gender effects in toxicology. Gender differences in toxicology begin at the gamete and embryo stage, continuing through development and maturation and into old age. Sex influences exposure, toxicokinetics, and toxicodynamics. The effects of sex have often been overlooked in both epidemiology and toxicology. In addition to the obvious modifying effects of the sex hormones and conditions affecting the male and female reproductive organs and sex roles, both genetic and hormonal effects influence many aspects of life and toxic responses. All aspects of toxicology should consider gender-balanced designs so that a more comprehensive understanding of differences and similarities can be obtained. Differential gene expression is a new frontier in toxicology. Risk assessment should account for gender and life cycle differences. The biological basis for altered sex ratios observed in several populations should be sought in animal models, and expanded to other compounds that might exert sex-selective effects. Wherever possible and feasible, toxicologic and environmental epidemiological studies should be designed and have sufficient statistical power to quantify differential gender-based exposures and outcomes.     

Industrial hygiene and national health objectives for the year 2000.

Industrial hygiene can have a powerful effect on family, community, and environmental health in addition to its effect on occupational health. Contemporary industrial hygiene begins in the workplace, but its impact can spread and improve the health status of the nation in several ways. Thirteen objectives for industrial hygiene are presented in this report. Industrial hygienists should know what the objectives are, how the objectives are useful to their practice, and how they can help to achieve them to improve the health of Americans.     

Knowledge management in occupational hygiene: the United States example

Knowledge management is an emerging field focusing on assessing the creation, transfer, and utilization of knowledge to address specific challenges. Generally, knowledge management has described efforts within and between companies to consider knowledge as a manageable asset. In this paper, we suggest that occupational hygiene knowledge can be considered a manageable asset by businesses and that the entire field of occupational hygiene in the USA can be appraised in terms of knowledge management. The knowledge cycle creates a foundation for knowledge management. Knowledge creation (research, recognition and evaluation), transfer (distribution, dissemination and diffusion), and utilization (risk management and control) make up the key elements of the knowledge cycle. Defining and understanding the roles of knowledge cycle elements facilitate the application of knowledge management to problems, systems, and situations in individual companies and in the field of occupational hygiene in general. Examples of current, effective knowledge management practices within occupational hygiene in the USA are described, and recommendations for further utilization of knowledge management principles are also presented.