The development and regulation of occupational exposure limits in Japan

The Ministry of Health, Labor and Welfare, on an administrative basis, establishes and supervises the Administrative Concentration Level, which can be viewed as an Occupational Exposure Limit (OEL) legally binding employers to maintain a good working environment. The Japan Society for Occupational Health, on a scientific basis, establishes the Recommended OELs, which can be viewed as a reference value for preventing adverse health effects on individual workers. In the case of carcinogens, Reference Values are recommended instead of OELs, corresponding to lifetime excessive risk of 10(-3) and 10(-4). The former is based on monitoring of the ambient working environment (area monitoring) while the latter is based on the monitoring of the individual worker. The two OELs influence each other in the course of establishment.     

The development and regulation of occupational exposure limits in Taiwan

The occupational exposure limits (OELs) in Taiwan was promulgated in 1974 and has been revised five times since then. Many of the OELs were adopted from the most recent ACGIH TLVs and US OSHA PELs. A total of 483 chemicals were listed in the current Taiwan OELs Standard. The procedures of OELs development in Taiwan include the IOSH organized a recommended exposure limits (RELs) Committee to select the target chemicals and to recommend the RELs through literature review based on the health effects in the first stage, then, the CLA put policy needs, economical and technical feasibility into consideration and set up the final OELs at the second stage. A standard operation manual of RELs Committee has been developed. Based on our experience, several issues including the participation of representatives from a comprehensive spectrum, communication/education and training/enforcement, continuous collection of the local exposure data and health hazard information, use of health risk assessment, consideration of economic, and technical feasibility, as well as the globalization and information and experience sharing are critical in developing the appropriate OELs. Three examples including benzene, crystalline silica, and 2-methoxy ethanol are given to demonstrate the operation of system.     

The development and regulation of occupational exposure limits in Singapore

Singapore is an island republic in South East Asia with a workforce of about 2.1 million including 0.7 million employed in the manufacturing industry. Singapore's industry is diversified and the main growth sectors include microelectronics, chemical, petrochemical, pharmaceutical, and biomedical sectors. Exposure to chemical hazards is one of the main occupational health problems in the manufacturing sectors. The main roles of government in the protection of workers against safety and health hazards are to set standards and provide a proper infrastructure for industry to self-regulate. The occupation safety and health laws must provide adequate protection of workforce but must not disadvantage local industry in this globally competitive economy. To ensure a level playing field, Singapore's occupational exposure standards are benchmarked against those established in the developed countries. These standards are reviewed regularly to ensure they are realistic and relevant in tandem with worldwide trends. Industry and stakeholders are consulted before any new standards are introduced. In enforcing the laws relating to exposure standards, legal and administrative procedures are followed to ensure fairness and to prevent abuse.     

The development and regulation of occupational exposure limits in Korea

With the institution of the new chemical regulatory framework in 2003, chemicals at the workplace have been classified into five categories; banned substances, permission-required substances, regulated substances, occupational exposure limit set substances, and other generally controlled substances. Currently, there are 698 substances with OELs. As we have come to gain our own experiences in the study and control of chemical hazards at the workplace such as the 2-bromopropane poisoning, OEL setting process has been streamlined. The OELs in Korea, however, remain merely as a recommendation, which does not require all the substances with OELs to be measured at the workplace. Coordination of whole program for hazardous chemicals including workplace measurement, OEL setting process, and enforcement activities is still needed in Korea.     

The development and implementation of occupational exposure limits in Hong Kong

The blooming of economy in Hong Kong started in 1950s. People witnessed the change from a rural town to a modern city. It required the participation of a large number of labours. The development of a list of "practical" hygiene standards for control of airborne contaminants in workplaces is important to protect the well beings of those workers. It follows the pace of economic changes, and it takes quite a long while for the current Code of Practice on Control of Air Impurities in workplace environment to be published. There had been a consultation with stakeholders, professional bodies, representatives of trades, and industries as well as other related parties before it was finalized in 2002. Although the Code of Practice comprises just more than 200 chemicals, its application will be monitored and reviewed. In light of new knowledge, it will be updated to ensure the workers could be well protected.     

New trends in the development of occupational exposure limits for airborne chemicals in China

Occupational exposure limits (OELs) are well established in many countries, which serve occupational professionals as benchmarks of industrial hygiene practice at workplaces worldwide. Starting in the mid-1950s, the central government of China began promulgating OELs for hazardous substances at workplaces. This paper discusses the historical basis, philosophical principles and schematic protocols of developing and setting OELs in China. The underlying principles include: (1) protection of human health being the first and the most important criterion; (2) the use of quantitative epidemiological studies in humans being given top priority; (3) integration and full use of all information sources, including animal experimental data for new chemicals or chemicals with new toxicity concerns; (4) considerations of socioeconomic and technological feasibilities in the country; and (5) amending existing standards based on new evidence. The strategy of the World Health Organization's "Two-step Procedure" is applied to convert health-based recommendations to law-based operational OELs, with considerations for national technological and socioeconomic conditions and priorities. As a result of the recent passage of the new law Occupational Diseases Prevention and Control Act of the People's Republic of China (ODPCAct), an official document Occupational Exposure Limits for Hazardous Agents in the Workplace containing a comprehensive list of new and amended OELs has been issued, which has now become one of the most essential regulations affiliated with the ODPCAct. This paper provides a brief summary of the salient features of the new law ODPCAct and the principles and processes of developing or amending OELs. This paper also discusses the challenges that lie ahead in enforcing the new regulations in China.     

Awareness and understanding of occupational exposure limits in Sweden

The efficiency of a risk management tool, such as occupational exposure limits (OELs), partly depends on the responsible parties’ awareness and understanding of it. The aim of this study was to measure the awareness and understanding of OELs at Swedish workplaces and to collect opinions on their use and function. Through a web-based questionnaire targeting workers that are exposed to air pollutants or chemicals, and persons working with occupational health and safety or in management at workplaces where workers are exposed to air pollutants or chemicals 1017 responses were collected. The results show that awareness and understanding of Swedish OELs is low among workers, as well as managers and occupational health and safety employees. Statistically significant, but small, differences were found depending on the size of the company and the position in the company. Based on the results, it is recommended that authorities and the social partners target this lack of awareness and understanding regarding OELs. Also, other tools to ascertain a safe working environment with regards to chemicals exposure might be useful for Swedish workplaces.     

Extensive changes to occupational exposure limits in Korea

Occupational exposure limits (OELs) are used as an important tool to protect workers from adverse chemical exposures and its detrimental effects on their health. The Ministry of Labor (MOL) can establish and publish OELs based on the Industrial Safety and Health Act in Korea. The first set of OELs was announced by the MOL in 1986. At that time, it was identical to the Threshold Limit Values of the American Conference of Governmental Industrial Hygienists. Until 2006, none the first OELs except for those of three chemicals (asbestos, benzene, and 2-bromopropane) were updated during the last twenty years. The Hazardous Agents Review Committee established under the MOL selected 126 chemicals from 698 chemicals covered by OELs using several criteria. From 2005 to 2006, the MOL provided research funds for academic institutions and toxicological laboratories to gather the evidence documenting the need to revise the outdated OELs. Finally, the MOL notified the revised OELs for 126 chemicals from 2007 to 2008. The revised OELs of 58 substances from among these chemicals were lowered to equal or less than half the value of the original OELs. This is the most substantial change in the history of OEL revisions in Korea.     

Strategy of the scientific committee on occupational exposure limits (SCOEL) in the derivation of occupational exposure limits for carcinogens and mutagens

Setting standards, such as occupational exposure limits (OELs) for carcinogenic substances must consider modes of action. At the European Union level, the scientific committee on occupational exposure limits (SCOEL) has discussed a number of chemical carcinogens and has issued recommendations. For some carcinogens, health-based OELs were recommended, while quantitative assessments of carcinogenic risks were performed for others. For purposes of setting limits this led to the consideration of the following groups of carcinogens. (A) Non-threshold genotoxic carcinogens; for low-dose assessment of risk, the linear non-threshold (LNT) model appears appropriate. For these chemicals, regulations (risk management) may be based on the ALARA principle ("as low as reasonably achievable"), technical feasibility, and other socio-political considerations. (B) Genotoxic carcinogens, for which the existence of a threshold cannot be sufficiently supported at present. In these cases, the LNT model may be used as a default assumption, based on the scientific uncertainty. (C) Genotoxic carcinogens with a practical threshold, as supported by studies on mechanisms and/or toxicokinetics; health-based exposure limits may be based on an established NOAEL (no observed adverse effect level). (D) Non-genotoxic carcinogens and non-DNA-reactive carcinogens; for these compounds a true ("perfect") threshold is associated with a clearly founded NOAEL. The mechanisms shown by tumour promoters, spindle poisons, topoisomerase II poisons and hormones are typical examples of this category. Health-based OELs are derived for carcinogens of groups C and D, while a risk assessment is carried out for carcinogens of groups A and B. Substantial progress is currently being made in the incorporation of new types of mechanistic data into these regulatory procedures.     

Scientific criteria used for the development of occupational exposure limits for metals and other mining-related chemicals

The scientific approaches employed by selected internationally recognized organizations in developing occupational exposure limits (OELs) for metals and other mining-related chemicals were surveyed, and differences and commonalities were identified. The analysis identified an overriding need to increase transparency in current OEL documentation. OEL documentation should adhere to good risk characterization principles and should identify (1) the methodology used and scientific judgments made; (2) the data used as the basis for the OEL calculation; and (3) the uncertainties and overall confidence in the OEL derivation. At least within a single organization, a consistent approach should be used to derive OELs. Opportunities for harmonization of scientific criteria were noted, including (1) consideration of severity in identification of the point of departure; (2) definition of the minimum data set; (3) approaches for interspecies extrapolation; (4) identification of default uncertainty factors for developing OELs; and (5) approaches for consideration of speciation and essentiality of metals. Potential research approaches to provide the fundamental data needed to address each individual scientific criterion are described. Increased harmonization of scientific criteria will ultimately lead to OEL derivation approaches rooted in the best science and will facilitate greater pooling of resources among organizations that establish OELs and improved protection of worker health.     

Derivation of occupational exposure limits: Differences in methods and protection levels

Frameworks for deriving occupational exposure limits (OELs) and OEL-analogue values (such as derived-no-effect levels [DNELs]) in various regulatory areas in the EU and at national level in Germany were analysed. Reasons for differences between frameworks and possible means of improving transparency and harmonisation were identified. Differences between assessment factors used for deriving exposure limits proved to be one important reason for diverging numerical values. Distributions for exposure time, interspecies and intraspecies extrapolation were combined by probabilistic methods and compared with default values of assessment factors used in the various OEL frameworks in order to investigate protection levels. In a subchronic inhalation study showing local effects in the respiratory tract, the probability that assessment factors were sufficiently high to protect 99% and 95% of the target population (workers) from adverse effects varied considerably from 9% to 71% and 17% to 87%, respectively, between the frameworks. All steps of the derivation process, including the uncertainty associated with the point of departure (POD), were further analysed with two examples of full probabilistic assessments. It is proposed that benchmark modelling should be the method of choice for deriving PODs and that all OEL frameworks should provide detailed guidance documents and clearly define their protection goals by stating the proportion of the exposed population the OEL aims to cover and the probability with which they intend to provide protection from adverse effects. Harmonisation can be achieved by agreeing on the way to perform the methodological steps for deriving OELs and on common protection goals.     

Scientific and practical considerations for the development of occupational exposure limits (OELs) for chemical substances

Occupational exposure limits (OELs) serve occupational health professionals as benchmarks for a healthy work environment. OELs are generally developed by manufacturers for substances which are not subject to governmental regulation or which have not been evaluated by consensus organizations such as the American Conference of Governmental Industrial Hygienists. This review is intended to serve as a practical guide to the standard-setting process. The discussion encompasses the evaluation of data, the different methods used for calculating limits, and the application of these limits to the workplace. The need for additional research to enhance the reliability of current methods is also discussed.     

Development of occupational exposure limits for the Hanford tank farms

Production of plutonium for the United States’ nuclear weapons program from the 1940s to the 1980s generated 53 million gallons of radioactive chemical waste, which is stored in 177 underground tanks at the Hanford site in southeastern Washington State. Recent attempts to begin the retrieval and treatment of these wastes require moving the waste to more modern tanks and result in potential exposure of the workers to unfamiliar odors emanating from headspace in the tanks. Given the unknown risks involved, workers were placed on supplied air respiratory protection. CH2MHILL, the managers of the Hanford site tank farms, asked an Independent Toxicology Panel (ITP) to assist them in issues relating to an industrial hygiene and risk assessment problem. The ITP was called upon to help determine the risk of exposure to vapors from the tanks, and in general develop a strategy for solution of the problem. This paper presents the methods used to determine the chemicals of potential concern (COPCs) and the resultant development of screening values and Acceptable Occupational Exposure Limits (AOELs) for these COPCs. A total of 1826 chemicals were inventoried and evaluated. Over 1500 chemicals were identified in the waste tanks headspaces and more than 600 of these were assigned screening values; 72 of these compounds were recommended for AOEL development. Included in this list of 72 were 57 COPCs identified by the ITP and of these 47 were subsequently assigned AOELs. An exhaustive exposure assessment strategy was developed by the CH2MHILL industrial hygiene department to evaluate these COPCs.     

The changing outlook of psychedelic drugs: The importance of risk assessment and occupational exposure limits

Serotonergic psychedelics, such as lysergic acid diethylamide (LSD), psilocybin, dimethyltryptamine (DMT), and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), are currently being investigated for the treatment of psychiatric disorders such as depression and anxiety. Clinical trials with psilocybin and LSD have shown improvement in emotional and psychological scores. Although these drugs are reported to be safe in a controlled environment (such as clinical trials), exposure to low doses of these drugs can result in psychedelic effects, and therefore, occupational safety is an important consideration to prevent adverse effects in the workplace from low daily exposure. This article will discuss the factors involved in the derivation of occupational exposure limits (OELs) and risk assessment of these psychedelic drugs. To support the OEL derivations of psychedelic drugs, information regarding their mechanism of action, adverse effect profiles, pharmacokinetics, clinical effects, and nonclinical toxicity were considered. Additionally, psilocybin and LSD, which are the most extensively researched psychedelic substances, are employed as illustrative examples in case studies. The OELs derived for psilocybin and for LSD are 0.05 and 0.002 μg/m³, respectively, which indicates that these are highly hazardous compounds, and it is important to take into account suitable safety measures and risk-management strategies in order to minimize workplace exposure.     

Sensory irritation as a basis for setting occupational exposure limits

There is a need of guidance on how local irritancy data should be incorporated into risk assessment procedures, particularly with respect to the derivation of occupational exposure limits (OELs). Therefore, a board of experts from German committees in charge of the derivation of OELs discussed the major challenges of this particular end point for regulatory toxicology. As a result, this overview deals with the question of integrating results of local toxicity at the eyes and the upper respiratory tract (URT). Part 1 describes the morphology and physiology of the relevant target sites, i.e., the outer eye, nasal cavity, and larynx/pharynx in humans. Special emphasis is placed on sensory innervation, species differences between humans and rodents, and possible effects of obnoxious odor in humans. Based on this physiological basis, Part 2 describes a conceptual model for the causation of adverse health effects at these targets that is composed of two pathways. The first, “sensory irritation” pathway is initiated by the interaction of local irritants with receptors of the nervous system (e.g., trigeminal nerve endings) and a downstream cascade of reflexes and defense mechanisms (e.g., eyeblinks, coughing). While the first stages of this pathway are thought to be completely reversible, high or prolonged exposure can lead to neurogenic inflammation and subsequently tissue damage. The second, “tissue irritation” pathway starts with the interaction of the local irritant with the epithelial cell layers of the eyes and the URT. Adaptive changes are the first response on that pathway followed by inflammation and irreversible damages. Regardless of these initial steps, at high concentrations and prolonged exposures, the two pathways converge to the adverse effect of morphologically and biochemically ascertainable changes. Experimental exposure studies with human volunteers provide the empirical basis for effects along the sensory irritation pathway and thus, “sensory NOAEC_human” can be derived. In contrast, inhalation studies with rodents investigate the second pathway that yields an “irritative NOAEC_animal.” Usually the data for both pathways is not available and extrapolation across species is necessary. Part 3 comprises an empirical approach for the derivation of a default factor for interspecies differences. Therefore, from those substances under discussion in German scientific and regulatory bodies, 19 substances were identified known to be human irritants with available human and animal data. The evaluation started with three substances: ethyl acrylate, formaldehyde, and methyl methacrylate. For these substances, appropriate chronic animal and a controlled human exposure studies were available. The comparison of the sensory NOAEC_human with the irritative NOAEC_animal (chronic) resulted in an interspecies extrapolation factor (iEF) of 3 for extrapolating animal data concerning local sensory irritating effects. The adequacy of this iEF was confirmed by its application to additional substances with lower data density (acetaldehyde, ammonia, n-butyl acetate, hydrogen sulfide, and 2-ethylhexanol). Thus, extrapolating from animal studies, an iEF of 3 should be applied for local sensory irritants without reliable human data, unless individual data argue for a substance-specific approach.     

Derivation of occupational exposure limits based on target blood concentrations in humans

An approach for deriving occupational exposure limits (OEL) for pharmaceutical compounds is the application of safety factors to the most appropriate pre-clinical toxicity endpoint or the lowest therapeutic dose (LTD) in humans. Use of this methodology can be limited when there are inadequate pre-clinical toxicity data or lack of a well-defined therapeutic dose, and does not include pharmacokinetic considerations. Although some methods have been developed that incorporate pharmacokinetics, these methods do not take into consideration variability in response. The purpose of this study was to investigate how application of compartmental pharmacokinetic modeling could be used to assist in the derivation of OELs based on target blood concentrations in humans. Quinidine was used as the sample compound for the development of this methodology though the intent was not to set an OEL for quinidine but rather to develop an alternative approach for the determination of OELs. The parameters for the model include body weight, breathing rate, and chemical-specific pharmacokinetic constants in humans, data typically available for pharmaceutical agents prior to large scale manufacturing. The model is used to simulate exposure concentrations that would result in levels below those that may result in any undesirable pharmacological effect, taking into account the variability in parameters through incorporation of Monte Carlo sampling. Application of this methodology may decrease some uncertainty that is inherent in default approaches by eliminating the use of safety factors and extrapolation from animals to humans. This methodology provides a biologically based approach by taking into consideration the pharmacokinetics in humans and reported therapeutic or toxic blood concentrations to guide in the selection of the internal dose-metric.     

Human exposure to airborne aniline and formation of methemoglobin: a contribution to occupational exposure limits

Aniline is an important starting material in the manufacture of polyurethane-based plastic materials. Aniline-derived methemoglobinemia (Met-Hb) is well described in exposed workers although information on the dose–response association is limited. We used an experimental design to study the association between aniline in air with the formation of Met-Hb in blood and the elimination of aniline in urine. A 6-h exposure of 2 ppm aniline in 19 non-smoking volunteers resulted in a time-dependent increase in Met-Hb in blood and aniline in urine. The maximum Met-Hb level in blood (mean 1.21 ± 0.29 %, range 0.80–2.07 %) and aniline excretion in urine (mean 168.0 ± 51.8 µg/L, range 79.5–418.3 µg/L) were observed at the end of exposure, with both parameters rapidly decreasing after the end of exposure. After 24 h, the mean level of Met-Hb (0.65 ± 0.18 %) returned to the basal level observed prior to the exposure (0.72 ± 0.19 %); whereas, slightly elevated levels of aniline were still present in urine (means 17.0 ± 17.1 vs. 5.7 ± 3.8 µg/L). No differences between males and females as well as between slow and fast acetylators were found. The results obtained after 6-h exposure were also comparable to those observed in four non-smoking volunteers after 8-h exposure. Maximum levels of Met-Hb and aniline in urine were 1.57 % and 305.6 µg/L, respectively. Overall, our results contribute to the risk assessment of aniline and as a result, the protection of workers from aniline-derived adverse health effects at the workplace.     

Defining occupational and consumer exposure limits for enzyme protein respiratory allergens under REACH

A wide range of substances have been recognized as sensitizing, either to the skin and/or to the respiratory tract. Many of these are useful materials, so to ensure that they can be used safely it is necessary to characterize the hazards and establish appropriate exposure limits. Under new EU legislation (REACH), there is a requirement to define a derived no effect level (DNEL). Where a DNEL cannot be established, e.g. for sensitizing substances, then a derived minimal effect level (DMEL) is recommended. For the bacterial and fungal enzymes which are well recognized respiratory sensitizers and have widespread use industrially as well as in a range of consumer products, a DMEL can be established by thorough retrospective review of occupational and consumer experience. In particular, setting the validated employee medical surveillance data against exposure records generated over an extended period of time is vital in informing the occupational DMEL. This experience shows that a long established limit of 60 ng/m³ for pure enzyme protein has been a successful starting point for the definition of occupational health limits for sensitization in the detergent industry. Application to this of adjustment factors has limited sensitization induction, avoided any meaningful risk of the elicitation of symptoms with known enzymes and provided an appropriate level of security for new enzymes whose potency has not been fully characterized. For example, in the detergent industry, this has led to general use of occupational exposure limits 3–10 times lower than the 60 ng/m³ starting point. In contrast, consumer exposure limits vary because the types of exposure themselves cover a wide range. The highest levels shown to be safe in use, 15 ng/m³, are associated with laundry trigger sprays, but very much lower levels (e.g. 0.01 ng/m³) are commonly associated with other types of safe exposure. Consumer limits typically will lie between these values and depend on the actual exposure associated with product use.     

Workshop report: Strategies for setting occupational exposure limits for engineered nanomaterials

Occupational exposure limits (OELs) are important tools for managing worker exposures to chemicals; however, hazard data for many engineered nanomaterials (ENMs) are insufficient for deriving OELs by traditional methods. Technical challenges and questions about how best to measure worker exposures to ENMs also pose barriers to implementing OELs. New varieties of ENMs are being developed and introduced into commerce at a rapid pace, further compounding the issue of OEL development for ENMs. A Workshop on Strategies for Setting Occupational Exposure Limits for Engineered Nanomaterials, held in September 2012, provided an opportunity for occupational health experts from various stakeholder groups to discuss possible alternative approaches for setting OELs for ENMs and issues related to their implementation. This report summarizes the workshop proceedings and findings, identifies areas for additional research, and suggests potential avenues for further progress on this important topic.