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.     

Procedures for health risk assessment in Europe

This report compares cancer classification systems, health risk assessment approaches, and procedures used for establishing occupational exposure limits (OELs), in various European countries and scientific organizations. The objectives were to highlight and compare key aspects of these processes and to identify the basis for differences in cancer classifications and OELs between various scientific organizations and countries. Differences in cancer classification exist in part due to differences in the ultimate purpose of classification and to the relative importance of different types of data (i.e., animal vs human data, mechanistic data, and data from benign vs malignant tumors). In general, the groups surveyed tend to agree on classification of chemicals with good evidence of carcinogenicity in humans, and agree less on classification of chemicals with positive evidence in animals and inadequate or limited evidence in humans. Most entities surveyed distinguish between genotoxic and nongenotoxic chemicals when conducting risk assessments. Although the risk assessment approach used for nongenotoxic chemicals is fairly similar among groups, risk assessment approaches for genotoxic carcinogens vary widely. In addition to risk assessment approaches, other factors which can affect OELs include selection of the critical effect, use of health-based vs technology-based exposure limits, and consideration of technological feasibility and socioeconomic factors.     

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.     

The development and regulation of occupational exposure limits in China

Of the 700 million workers in China, approximately 200 million workers are potentially exposed to industrial hazards. Although the promulgation and implementation of occupational exposure limits (OELs) in China began in the mid-1950, a systematic approach was not formalized until the formation of the Subcommittee of Occupational Health Standards Setting (SOHSS) in 1981. More recently, the 2002 Occupational Disease Prevention and Control Act of the People's Republic of China created the legislative framework for the development and enforcement of OELs. The SOHSS, whose members are primarily health professionals, is the organization responsible for the development of recommended standards, under the auspices of the Ministry of Health. The philosophy of OEL development of the SOHSS consists of a two-step approach: (1) an initial health-based recommended standard is established based on scientific data, and (2) a final law-based standard takes into consideration both socioeconomic and technological feasibility. Governmental agencies such as the Centers for Diseases Control and Prevention and the Institutes of Public Health Supervision at the state, provincial or municipal levels are charged with the responsibilities of the enforcement of OELs. The process and challenges in the enforcement of OELs are discussed. A comparison is made between selected Chinese OELs and those in other countries. The OELs for benzene and industrial dusts (including silica) are discussed in some detail.     

Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.     

Implications of hormesis for industrial hygiene

This paper considers hormesis as a valid and potentially valuable alternative hypothesis for low-dose response in the context of occupational health risk assessment. It outlines the current occupational risk assessment paradigm and its use of high-dose toxicological data in setting occupational exposure limits (OELs). This present effort is a call to science to investigate the potential promise of hormesis in providing prima facie experimental evidence for a low-dose threshold of toxic effect to chemical agents. The scientific effort and advancement advised in this piece could also lead to experimentally validated quantitative estimates of the toxic effect extant at occupational exposures in the region of the OEL.     

Does EU legislation allow the use of the Benchmark dose (BMD) approach for risk assessment?

Hazard characterisation is largely based on an approach of (statistically) comparing dose groups with the controls in order to derive points of departure such as no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs). This approach suggests the absence of any relevant effect at the NOAEL. The NOAEL approach has been debated for decades. A recent Scientific Opinion by the European Food Safety Authority (EFSA) concluded that the Benchmark Dose (BMD) approach should be preferred over the NOAEL approach for deriving human (health-based) limit or guidance values. Nonetheless, the BMD approach is used infrequently within European regulatory frameworks. The reason for this may lie in legislation or guidelines requiring the use of the NOAEL approach. In this context, various EU regulatory frameworks were examined on such demands. Interestingly, no single legislation was identified containing statutory requirements in conflict with the use of the BMD approach.     

Comments: implications of hormesis for industrial hygienists

Quantitative health risk assessment is based on extrapolating from the high-dose end of the dose-response curve to points close to the origin or the threshold where the dose levels are closer to the lower environmental or occupational exposures. Hormesis is demonstrated in chronic toxicological studies where the animals treated at the lowest experimental dose appear to be healthier than the controls, as evidenced by longer life spans, less disease and/or increased body weight. If the occupational exposure limit (OEL) or environmental exposure limit (EEL) is in the range of the hormetic effect, or lower than the hormetic effect, then a case could be made that exposure at the OEL or EEL is 'safe.' This idea is controversial because it challenges some of the basic assumptions of quantitative health risk assessment as it has been practiced during the past 50 years. De-emphasis of the dose-response curve in determining OELs and EELs will occur not because of hormesis, but because the emerging sciences of genomics and proteomics will shift the focus from statistical methods to individuals as genetic and protein engineering becomes more sophisticated and powerful.     

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.     

The utility of PBPK in the safety assessment of chloroform and carbon tetrachloride

Occupational exposure limits (OELs) for individual substances are established on the basis of the available toxicological information at the time of their promulgation, expert interpretation of these data in light of industrial use, and the framework in which they sit. In the United Kingdom, the establishment of specific OELs includes the application of uncertainty factors to a defined starting point, usually the NOAEL from a suitable animal study. The magnitude of the uncertainty factors is generally determined through expert judgment including a knowledge of workplace conditions and management of exposure. PBPK modeling may help in this process by informing on issues relating to extrapolation between and within species. This study was therefore designed to consider how PBPK modeling could contribute to the establishment of OELs. PBPK models were developed for chloroform (mouse and human) and carbon tetrachloride (rat and human). These substances were chosen for examination because of the extent of their toxicological databases and availability of existing PBPK models. The models were exercised to predict the rate (chloroform) or extent (carbon tetrachloride) of metabolism of these substances, in both rodents and humans. Monte Carlo analysis was used to investigate the influence of variability within the human and animal model populations. The ratio of the rates/extent of metabolism predicted for humans compared to animals was compared to the uncertainty factors involved in setting the OES. Predictions obtained from the PBPK models indicated that average rat and mouse metabolism of carbon tetrachloride and chloroform, respectively, are much greater than that of the average human. Application of Monte Carlo analysis indicated that even those people who have the fastest rates or most extensive amounts of metabolism in the population are unlikely to generate the levels of metabolite of these substances necessary to produce overt toxicity in rodents. This study highlights the value that the use of PBPK modeling may add to help inform and improve toxicological aspects of a regulatory process.     

Evaluation of airborne sensory irritants for setting exposure limits or guidelines: A systematic approach

Sensory irritation of eyes and upper airways is an important endpoint for setting occupational exposure limits (OELs) and indoor air guidelines. Sensory irritants cause a painful burning, stinging and itching sensation. Controlled chamber studies are the “golden standard” for evaluations. Well conducted workplace studies offer another possibility. For generalization, the number of participants and their age, smoking, gender, and prior exposure, experience and mood has to be considered. Exposure assessments have to be reliable and exposure duration sufficiently long to establish time-response relationships. A potential confounding by odour has to be assessed. For workplace exposures, mixed exposure and healthy worker effects have to be evaluated. The “Alarie test” is the only validated animal bioassay for prediction of sensory irritation in humans. The mouse bioassay uses the trigeminal reflex-induced decrease in the respiratory rate. The 50% decrease (RD₅₀) has been correlated with OELs set for sensory irritants; predicted OELs for sensory irritants are 0.03xRD₅₀. Evaluation of the bioassay comprises the number of mice and the strain, the reliability of the exposure concentrations and exposure-response relationships, and the similar mode-of-action in mice and humans. These approaches can be used for quality assurance of reported data to set air quality guidelines.     

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.     

Deriving a data-based interspecies assessment factor using the NOAEL and the benchmark dose approach

In deriving human health-based exposure limits from animal data, differences in sensitivity to a compound between animals and humans must be taken into account. These interspecies differences can be caused by differences in toxicokinetics and or toxicodynamics. Apart from that, species differ in body size, and this is usually accounted for by scaling doses to body weight (i.e., expressed as mg/kg body weight1.0/day).Adefault assessmentfactor (AF) of 10 is commonly applied to this dose metric to account for potential toxicokinetic and toxicodynamic differences. However, both proportional body weight (BW)scalingand the defaultAFas often applied are not directly based on empirical findings. Attempts have been made to derive data-based assessment factors and allometric scaling powers using various toxicological values such as no-observedadverse-effect-levels (NOAELs). In thisstudy both the NOAEL approach and the benchmark dose (BMD) approach are applied to deriveNOAEL ratios and BMD ratios from mouse and rat studies and, based on that information, toestimate an allometric scaling power and an interspecies AF. To account for interspecies differences in body size, our results confirm earlier findings that allometric body weight scaling with a power of around 0.7 is appropriate. The factor needed to rescale the dose in terms of mg/kgBWto the allometric dose scale ranges from around 1.7 (for dogs) to 10(for mice), similar to other findings. The additional factor required for taking into account interspecies toxicokinetic and toxicodynamic differences, when based on the 95th percentile of the relevant ratio distribution, would be 3.1 for a lower Confidence limit of theBMD (BMDL), and 8.3 for a NOAEL (to be applied to the allometrically scaled dose). These results indicate that the generally used defaultAFof 10 may not cover potential interspecies differences, in particular when applied to results from smaller test species. Therefore, using the default AF of 10 could lead to human exposure limits that are insufficiently protective. Further, our results show that a data-based AF that would be needed for interspecies extrapolation is smaller when the point of departure is aBMDLrather than a NOAEL. In the context of a probabilistic hazard characterization, our results indicate that the (geometric) SD of the interspecies AF distribution should be around 2.0 when the BMDL (or BMD uncertainty distribution) is used, and around 3.4 when the NOAEL is used as a point of departure for further risk assessment.     

Deriving a Data-Based Interspecies Assessment Factor Using the NOAEL and the Benchmark Dose Approach

In deriving human health-based exposure limits from animal data, differences in sensitivity to a compound between animals and humans must be taken into account. These interspecies differences can be caused by differences in toxicokinetics and or toxicodynamics. Apart from that, species differ in body size, and this is usually accounted for by scaling doses to body weight (i.e., expressed as mg/kg body weight1.0/day).Adefault assessmentfactor (AF) of 10 is commonly applied to this dose metric to account for potential toxicokinetic and toxicodynamic differences. However, both proportional body weight (BW)scalingand the defaultAFas often applied are not directly based on empirical findings. Attempts have been made to derive data-based assessment factors and allometric scaling powers using various toxicological values such as no-observedadverse-effect-levels (NOAELs). In thisstudy both the NOAEL approach and the benchmark dose (BMD) approach are applied to deriveNOAEL ratios and BMD ratios from mouse and rat studies and, based on that information, toestimate an allometric scaling power and an interspecies AF. To account for interspecies differences in body size, our results confirm earlier findings that allometric body weight scaling with a power of around 0.7 is appropriate. The factor needed to rescale the dose in terms of mg/kgBWto the allometric dose scale ranges from around 1.7 (for dogs) to 10(for mice), similar to other findings. The additional factor required for taking into account interspecies toxicokinetic and toxicodynamic differences, when based on the 95th percentile of the relevant ratio distribution, would be 3.1 for a lower Confidence limit of theBMD (BMDL), and 8.3 for a NOAEL (to be applied to the allometrically scaled dose). These results indicate that the generally used defaultAFof 10 may not cover potential interspecies differences, in particular when applied to results from smaller test species. Therefore, using the default AF of 10 could lead to human exposure limits that are insufficiently protective. Further, our results show that a data-based AF that would be needed for interspecies extrapolation is smaller when the point of departure is aBMDLrather than a NOAEL. In the context of a probabilistic hazard characterization, our results indicate that the (geometric) SD of the interspecies AF distribution should be around 2.0 when the BMDL (or BMD uncertainty distribution) is used, and around 3.4 when the NOAEL is used as a point of departure for further risk assessment.     

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.     

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.     

Evaluation of subchronic toxicity data using the benchmark dose approach

We used the benchmark dose (BMD) methodology devised by Crump (Fundam. Appl. Toxicol. 4, 854-871, 1984) to estimate BMDs for 90-day toxicological data and several fabricated data sets. From a toxicological perspective, dose-response modeling offers certain advantages over using a point estimate, such as the currently used no-observable-adverse-effect level (NOAEL) approach. However, there are many variables associated with the BMD that could be set to produce unreasonable BMD estimates. Some of these variables and decisions are examined in this study. BMDs were calculated for discrete and continuous endpoints using a variety of different variables (e.g., maximum likelihood estimates [MLEs], lower-confidence limits [LCLs], and different risk levels). In addition, the fabricated data sets were manipulated (i.e., dose groups eliminated) and the BMDs recalculated. This process tested how the BMD estimates varied using different forms of the data. For the 90-day toxicological studies, the BMDs were typically within an order of magnitude of the NOAEL for discrete endpoints. For the discrete endpoints, the MLEs were typically greater than the NOAEL and the LCLs were typically less than the NOAEL. The BMD was insensitive to changes in the data points one to two dose groups beyond the NOAEL/LOAEL. With the continuous data, the ratios of MLEs and LCLs to the NOAEL were highly variable, and no general trend could be determined. The BMD methodology offers potential improvements in the risk assessment process since dose-response characteristics are used to calculate the BMD. Depending upon how the BMD is defined, i.e., the form of the dose-response model, and how the BMD is used in the risk assessment process, BMD estimates may produce reference doses/concentrations that are more or less conservative than the NOAEL approach. Active involvement in discussions with regulatory agencies is needed to ensure that inappropriate models and unreasonable BMDs are not used. In addition, further discussions on how BMDs should be used in the risk assessment process are needed.     

Development of an occupational exposure limit for n-propylbromide using benchmark dose methods

This paper presents the development of an occupational exposure level (OEL) for n-propylbromide (nPB) using benchmark dose methods. nPB is a non-ozone depleting solvent, proposed under the Significant New Alternatives Policy (SNAP) for use as a precision vapor degreaser. OELs have generally been developed on the basis of a NOAEL or LOAEL and application of uncertainty factors; this paper represents a departure from historic methods. Six recently completed toxicological studies were critically reviewed to identify (1) toxicologically significant endpoints, (2) dose-response information on these endpoints, and (3) uncertainties and limitations associated with the studies. Dose-response data were compiled and entered into the USEPA's benchmark dose software for calculation of a benchmark dose (BMD) and a benchmark dose low (BMDL). Once values were estimated for all relevant studies, they were then incorporated into a weight-of-evidence approach to develop a single BMD and BMDL representative of nPB. This approach is similar to that recently taken by USEPA to develop their own recommended OEL for nPB. USEPA's approach is compared and contrasted with ours, particularly in relation to the application of uncertainty factors (UFs) to generate a final OEL. There are no published criteria for application of UFs in developing an OEL. Although USEPA recommends utilizing a UF of 9, based on intraspecies variability and pharmacokinetic differences between rats and humans, to meet the goal of protecting healthy adult in a workplace setting, no uncertainty factor was deemed necessary for nPB in this paper. Therefore, the BMDL was recommended as the OEL.     

Occupational exposure limits in Europe and Asia--continued divergence or global harmonization?

Occupational exposure limits (OELs) are used as a risk management tool aiming at protecting against negative health effects of occupational exposure to harmful substances. The systems of OEL development have not been standardized and divergent outcomes have been reported. However some harmonization processes have been initiated, primarily in Europe. This study investigates the state of harmonization in a global context. The OEL systems of eight Asian and seventeen European organizations are analyzed with respect to similarities and differences in: (1) the system for determining OELs, (2) the selection of substances, and (3) the levels of the OELs. The majority of the investigated organizations declare themselves to have been influenced by the American Conference of Governmental Industrial Hygienists (ACGIH), and in many cases this can be empirically confirmed. The EU harmonization process is reflected in trends towards convergence within the EU. However, comparisons of Asian and European organizations provide no obvious evidence that OELs are becoming globally harmonized.     

Are occupational exposure limits becoming more alike within the European Union?

The occupational exposure limits (OELs) established by seven different national regulatory agencies of EU member states are compared with those of the European Commission (EC). The comparison concerned: (1) what chemicals have been selected, (2) the average level of exposure limits for all chemicals, and (3) the similarity between the OELs of different EU member states and the OELs recommended by the European Commission. The average level of the exposure limits has declined during the past 10 years in four of the five countries in our study for which historical data were available to us. Poland has not changed its level noticeably and Germany has increased it. Since the first list of indicative OELs was established by the EC, a few of the EU exposure limits have been lowered. The similarity index indicates that the exposure limits of EU member states are converging towards the European Commission's recommended OELs. Still, the average level of OELs differs between organizations--the Estonian OELs are on average 35% higher than the Polish OELs.