Introduction
Occupational exposure limit values (OELs) are set to prevent occupational diseases or other adverse effects in workers exposed to hazardous chemicals in the workplace. OELs assume that exposed persons are healthy adult workers, although in some cases the OELs should also protect vulnerable groups – e.g. pregnant women or other more susceptible people. They are tools to help employers protect the health of workers who may be exposed to chemicals in the working environment. OELs are usually set for single substances, but sometimes they are also produced for common mixtures in the workplace, for example solvent mixes, oil mists, fumes from welding or diesel exhaust fume.
Basic definitions
Council Directive 80/1107/EEC, as amended by Council Directive 88/642/EEC, on the protection of workers from the risks related to exposure to chemical, physical and biological agents at work, introduced into EU legislation of the objective of establishing occupational exposure limits (OELs)[1]. OEL means the limit of the time-weighted average of the concentration of a chemical agent in the air within the breathing zone of a worker in relation to a specified reference period[2].
This Directive sets out general principles for assessing and preventing risks at work from the use of chemical agents, and includes the legal framework for indicative occupational exposure limit values (IOELVs), binding occupational exposure limit values (BOELVs) and binding biological limit values:
- ‘Indicative’ OELs are health-based limits conventionally established only for substances for which it is possible to establish a threshold or a no effect level considered to be protective of health. To establish OEL, a thorough assessment of the available scientific information is essential as a first step. This is undertaken by the European Commission’s Scientific Committee for Occupational Exposure Limits (SCOEL). These limit values should be established or revised taking into account the availability of measurement techniques. Member States should keep workers' and employers' organisations informed of IOELVs set at a Community level. For any chemical for which an IOELV is established at a Community level, Member States should establish a national occupational exposure limit value, taking into account the Community limit value, determining its nature in accordance with national legislation and practice[2].
- ‘Binding’ OELs (BOELVs) may be drawn up at a Community level and, in addition to the factors considered when establishing IOELVs, socio-economic and technical feasibility factors should be taken into account and intend to provide a level of minimum protection for all workers in the Community. For any chemical agent for which a BOELV is established, Member States should establish a corresponding national binding occupational exposure limit value based on, but not exceeding the Community limit value.
- Biological Limit Values (BLVs) are reference values for the evaluation of potential health risks in the practice of occupational health. They are established by SCOEL on the basis of currently available scientific data. The BLVs define maximum levels of substances in humans, their metabolite, or indicator of effect e.g. in blood, urine or breath. For many substances, the data are too limited to support a biological monitoring method, or a metabolite or indicator cannot be defined. In general, SCOEL set BLVs for compounds with skin notation as a priority[3][4].
- ‘Binding’ biological limit values (BBLVs) may be drawn up at a Community level on the basis of evaluation as described for IOELVs and on the availability of measurement techniques, and should reflect feasibility factors while maintaining the aim of ensuring the health of workers at work. For any chemical agent for which a binding biological limit value is established, Member States should establish a corresponding national binding biological limit value based on, but not exceeding, the Community limit value. The BBLV is established for lead and its ionic compounds[2].
- In many European countries, a skin notation is used to warn about skin contact where it can add significantly to the body burden, in addition to that caused by inhalation. Skin notation setting is not standardised across countries and agencies. In Germany, a skin notation is set from clinical experiences (e.g. casuistics), animal studies (e.g. dermal doses that can cause toxic effects or percutaneous absorption), from in vitro studies and from theoretical models[5]. In Poland, the skin notation is set mainly based on a high dermal toxicity in experimental animals[6]. A skin notation assigned to an OEL by the SCOEL identifies the possibility of significant uptake through the skin. The SCOEL will use all available information as a basis for making an assessment of whether or not the criteria for application of a skin notation are met (direct measurement of percutaneous absorption in humans or animals, comparison of dermal and intravenous or intraperitoneal toxicity, physicochemical data, including volatility, or structure/activity relationships)[3][4].
When selecting candidate priority substances for setting OELs in the EU, the following criteria are taken into account:
- Epidemiological evidence including reported cases of ill-health in the workplace
- Availability of toxicological data
- Severity of effects
- Number of persons exposed
- Availability of data on exposure
- Availability of measurement methods
The process of harmonising exposure limits in EU countries began with the establishment of IOELVs by the Scientific Committee on Occupational Exposure Limits to Chemical Agents (SCOEL), an advisory body of the European Commission. The first stage in the OEL setting process is to assemble all the information available on the hazards of the substance and decide whether this provides an adequate database on which to proceed. The SCOEL prepares a short summary document (SCOEL/SUM) on each compound, and, if the SUM document is agreed upon by the SCOEL members, it is circulated to interested parties for comments. After a comment period of about 6 months, the SCOEL re-discusses the document in light of the received comments. After clarification of the raised questions, the final version is adopted and submitted to the Commission for publication. When the European Commission disposes of a sufficient number of approved SCOEL recommendations, it prepares a draft Commission Directive setting out proposed new IOELVs. This is transmitted to the Advisory Committee on Safety and Health at Work with an opinion from the Working Party on Chemicals in the Workplace (a subgroup of the Advisory Committee for Safety and Health at Work). The Advisory Committee gives its opinion on the proposal, if necessary establishing its view by means of a vote. If the Advisory Committee has an agreed position in favour of the proposal, the Commission invites all Member states to vote on the proposed IOELV Directive. If the Commission’s proposal receives a qualified majority, the Commission adopts the Directive and it is published in the Official Journal of the European Union. Member States then have a fixed timescale (typically 18 months) to implement the Directive in their national legislation[7][3].
OELs are usually expressed as milligram per cubic meter (mg/m3) of air, which can be converted to parts per million (ppm) for gases and vapours, corresponding to cm3 of gases or vapours per m3 of air. At 1 atm and 25 °C, the conversion is 1 ppm = (the molecular weight of the compound) /24.45 mg/m3. OELs for non-volatile airborne particulates (dust, smoke and vapours) are given in mg/m3, except for fibres, where the OELs are often set as a number of fibres per cm3 [7]. On the national level, the Ministry of Labour is responsible for establishing these values in most EU countries[8].
OELs are usually established for single substances. When two or more harmful substances, which act upon the same target organ, are present, their combined effect, rather than that of either individually, should be taken into account. In the absence of information to the contrary, the effects of the different hazards should be considered as additive.
When there is a good reason to believe that the principal effects of the different harmful substances are, in fact, not additive but independent, as when purely local effects on different organs of the body are produced by the various components of the mixture, then the above rule cannot be applied. In such cases, the occupational exposure limit value for the mixture is exceeded only when at least one member of the series (C1/OELV1 or C2/OELV2 etc.), itself, has a value exceeding unity. The same situation applies for carcinogens and mutagens. Synergistic effects, when substances combine to give a greater effect than expected from simple linear addition, may occur with some combinations of atmospheric contaminants; such cases at present must be determined individually[7].
The European Union to date has only set a limited number of OELs. Many countries have set more limit values, making use of similar criteria and after assessment in national scientific committees and consultation with interested parties.
Health effects of chemicals and OELs
Chemical substances occur in the form of gases, vapours, liquids, dusts or fumes in the working environment. They are absorbed into the body mostly through the respiratory tract and skin or from the gastrointestinal tract. Gases and vapours are absorbed directly by the respiratory tract, depending on the physical activity. Fumes in the liquid phase can be absorbed directly by the pulmonar alveoli (terminal dilations of the air passageways). Biopersistent aerosols (dusts and fumes) are not totally absorbed – some dusts can be eliminated with mucus, coughed up with sputum or swallowed.
The body’s response to chemicals depends on the dose/concentration, the chemicals’ physicochemical properties and absorption route, the health, sex and age of the exposed person and the condition of both the endocrine (hormonal) and immune systems, in addition to external factors such as temperature, exposure period and humidity.
If harmful effects of a substance occur in a relatively short period of time (within 24 hours), it indicates an acute type of exposure. This most often happens with a sudden event, referred to as an ‘accident’ at work. When harmful effects occur after prolonged exposure to low doses or concentrations of substances present in the workplace, it is a chronic type of exposure. Occupational exposure is usually chronic.
Harmful (hazardous, dangerous) substances are the substances that can cause adverse effects, including (sensory) irritation from the airways and the eyes, headache, as well as sedation and narcotic effect depending on the dose (the amount of substance that is ingested, inhaled, or absorbed through the skin). Research methods on the toxicity of chemicals and principles of classification are globally harmonised. A list of dangerous substances can be found in European directives. They fall into at least one of the following categories, according to health effect: highly toxic, toxic, harmful, corrosive irritant, sensitising, carcinogenic, mutagenic, toxic for reproduction[9].
The first stage in the OEL setting process is to assemble all the information available on the hazards of the substance, as well as physicochemical properties. High quality human data (individual case reports, studies in human volunteers, or cohort and case-control studies) are preferred to animal data, but frequently may not be available, and clear dose-response relationships (the change in effect on an organism caused by different doses or concentrations after exposure time) are rarely demonstrated. The second stage is to identify the adverse effects that may arise from exposure to the substance, and then establish which adverse effect is crucial in deriving the level of OEL. From the key study (or studies) describing the critical effect(s) of chemical, the No Observed (Adverse) Effect Level (NO(A)EL) is established. In those cases where it is not possible to establish a NO(A)EL, a Lowest Observed (Adverse) Effect Level (LO(A)EL) may be determined:[4]
The NOAEL (No Observed Adverse Effect Level) is the highest level of a test substance to which organisms can be exposed without causing any observed and statistically significant adverse effects on the organism compared with the controls.
The LOAEL (Lowest Observed Adverse Effect Level) is the lowest level of a test substance, to which organisms can be exposed causing an adverse alteration of morphology, functional capacity, growth, development, or life span of a target organism compared with the control organisms of the same species and strain under defined conditions of exposure.
The NOAEL is the common point of departure in establishing OELs. The OELs are set lower than the experimentally determined NOAEL due to the imprecision of the data and differences in sensitivity between and within species. Additionally, the length of the study, extrapolation from the LOAEL to the NOAE, as well as an incomplete database is taken into account[4].
For the majority of substances, only data from animals are available, and the OEL may be set by dividing the NOAEL by uncertainty factors (UFs, also termed safety factors and assessment factors, AFs). UFs are used in the process of extrapolating animal data to humans, route-to-route extrapolation, differences between species, intraspecies, exposure duration, dose-response and the quality of the whole database[10]. There are large differences between UFs listed in the European Regulation on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) to establish DNELs (Derived No-Effect Levels)[11], and others used by the SCOEL to establish OELs[4] or proposed by the European Centre for Ecotoxicology and Toxicology of Chemicals[12] to derive DNELs.
There are two main groups of substances for which NOAEL cannot be identified: respiratory sensitisers acting via immunological mechanisms and genotoxic carcinogens.
The SCOEL takes into account available information on groups of people at special risk. However, the variability of response between individuals at the same level of exposure, and the existence of special risk groups, may mean that the recommended OEL may not provide adequate protection for every individual. Depending on the specific chemical database, SCOEL might not recommend a health-based OEL for certain chemicals. In the workplace, sensitisers may affect the respiratory system (and the conjunctiva) and also the skin. For some substances (for example those causing respiratory sensitisation via non-immunological mechanism) it might be possible to identify a threshold of exposure below which a state of sensitisation is unlikely to be induced. It is considered unlikely that such a threshold could be identified for substances acting via immunological mechanisms. Where sufficient data are not available, the SCOEL cannot set a health-based OEL and it recommends only a ‘sensitisation notation’ in the front of documentation. The SCOEL also takes the view that it is not possible to set health based OELs which will provide protection against the elicitation of responses among persons who have already become sensitised to particular substances[4].
Some substances show adverse effects on reproduction at exposure levels considerably lower than those causing other forms of toxicity. Because of the relative sensitivity of the rapidly developing individual to specific toxic effects, OELs established to protect adults cannot a priori guarantee the absence of pre- or post-natal adverse effects. Young people, pregnant or lactating women may represent a special risk group in the workplace[13]. According to Council Directive 89/391/EEC[14], Council Directive 92/85/EC[15] on pregnant workers and Council Directive 94/33/EC[16] on young people at work, the SCOEL, when recommending OELs, consider reproductive effects along with all other aspects of toxicity and recommending OEL is sufficiently low to protect workers against such adverse effects[4].
Occupational exposure limits for carcinogenic compounds
Exposure to some chemicals can cause uncontrolled growth of cells leading to cancer. For most carcinogenic substances, an effect threshold cannot be determined. For a long time, occupational exposure limits for non-genotoxic carcinogens have been established, but it is extremely difficult to derive a safe level of exposure to a genotoxic carcinogen (genotoxic substances – substances that damage genetic material).
For carcinogenic substances in many countries, exposure limits are not established because it is not possible to determine safe exposure levels. Instead of proposing an exposure limit, a quantitative risk assessment may be carried out. Different government agencies and national or international organisations active in establishing or proposing admissible exposure levels for carcinogenic substances use the concept of so-called acceptable risk. The level of acceptable risk depends on commonly accepted social and economic criteria. In this respect, the decision is usually taken by three interest groups comprised of employee representatives, employers and state administrators, whose task is to perform law enforcement surveillance. A few Member States (e.g. Germany, the Netherlands, Poland) are reported to apply criteria on acceptability of risk[17][8].
Determination of IOELVs (indicative occupational exposure limit values) for carcinogenic substances by the European Scientific Committee on Occupational Exposure Limits (SCOEL) depends on the type and mechanism of their carcinogenic effect, that is, on whether or not the substance produces genotoxic effects. Thus, carcinogenic substances have been divided into the following groups by the SCOEL:
- Group A – non-threshold genotoxic carcinogens: Risk assessment involves a linear non-threshold (LNT) model of extrapolation of test results from animals (high doses) to humans (low doses); e.g. 1,3-butadiene, vinyl chloride and dimethyl sulfate.
- Group B – genotoxic carcinogens: The existing data are not sufficient to apply the LNT model; e.g. acrylonitrile, benzene, naphthalene and wood dusts.
- Group C – genotoxic carcinogens: A practical threshold can be set based on existing data; e.g. formaldehyde, vinyl acetate, nitrobenzene, pyridine, crystalline silica and lead.
- Group D – non-genotoxic and non DNA-reactive carcinogens: A threshold can be set based on NOAEL; e.g. example, carbon tetrachloride and chloroform.
Health-based OELs are derived by the Scientific Committee on Occupational Exposure Limits only for carcinogens of groups C and D[18][4].
Where possible, a health risk assessment for regulating carcinogens should be based on epidemiological studies. However, this approach is only possible for a limited number of compounds, and risk assessment has to be based on animal studies in most instances. In this case, several points of departure are used in risk assessments in combination with various extrapolation models[7].
Short term exposure limits (STEL) and ceiling (STEL-C)
Some substances have set short term exposure limits (STELs). STEL is the concentration that workers can be exposed to continuously for a short period of time without risking acute effects, such as throat irritation, that will not be controlled by the application of an 8-hour OEL. In these cases, one substance has two limit values. In addition to the ‘normal’ 8-hour OEL, there is a STEL. These exposure limits are often set for 15 minutes and referred to as Short-Term Exposure Limits – 15 minutes. Some countries have also limited the frequency of peaks to a maximum of 4 peaks/day with a minimal interval of 1 hour. Short term exposure limits are intended for use in normal work situations. They must not be used to protect against emergency situations. The European Scientific Committee on Occupational Exposure Limits has established STELs for substances, usually related to 15 minutes, based on a case-by-case review of available data[4].
For other substances, peak concentrations are determined, where this level should not be exceeded during any time of the workday. A ceiling limit may be set without setting an OEL. Ceiling exposure limits are used for substances, for which short-term peaks of exposure could result in serious health effects – for example, respiratory irritants such as chlorine. For those substances, continuous, direct-reading or short-term instantaneous measurements should be available. If such monitoring is not feasible, sampling should be conducted for the minimum period of time sufficient to detect exposure at or above ceiling value[19].
Legislative aspects
The European Union has established a legal basis for setting OELs and Biological Limit Values for chemicals with a threshold effect. The OELs are termed Indicative Occupational Exposure Limit Values (IOELV), and they are established by the SCOEL (Scientific Committee on Occupational Exposure Limits). IOELVs are health-based, non-binding values established on the basis of the latest data and with the use of available measuring techniques. They determine threshold exposure levels below which exposure is not expected to lead to adverse effects. IOELVs are necessary for determination and assessment of risk incurred by the employer in accordance with Art. 4 of Council Directive 98/24/EC of 7 April 1998 on the protection of the health and safety of workers from the risks related to chemical agents at work(fourteenth individual Directive within the meaning of Article 16(1) of Directive 89/391/EEC)[2]. They have to be considered by the Member States when establishing their own national OELs.
The indicative occupational exposure limit values are published in four directives: Commission Directive 91/322/EEC of 29 May 1991 on establishing indicative limit values by implementing Council Directive 80/1107/EEC on the protection of workers from the risks related to exposure to chemical, physical and biological agents at work[20], Commission Directive 2000/39/EC of 8 June 2000 establishing a first list of indicative occupational exposure limit values in implementation of Council Directive 98/24/EC on the protection of the health and safety of workers from the risks related to chemical agents at work[21], Commission Directive 2006/15/EC of 7 February 2006 establishing a second list of indicative occupational exposure limit values in implementation of Council Directive 98/24/EC and amending Directives 91/322/EEC and 2000/39/EC[22] and Commission Directive 2009/161/EU of 17 December 2009 establishing a third list of indicative occupational exposure limit values in implementation of Council Directive 98/24/EC and amending Commission Directive 2000/39/EC[23].
For some non-threshold carcinogenic substances for which indicative occupational exposure limit values (IOELVs) cannot be set, Binding Occupational Exposure Limit Values – BOELVs have been adopted. They are established on the basis of currently available scientific data, socio-economic criteria and technical possibilities to achieve these values in the industry. Binding values have been set for the following substances: asbestos (actinolite, anthophyllite, chrysotile, grunerite, crocidolite, tremolite), benzene, hardwood dusts, lead and its inorganic compounds, vinyl chloride monomer[2]; Directive 2003/18/EC of the European Parliament and of the Council of 27 March 2003 amending Council Directive 83/477/EEC on the protection of workers from the risks related to exposure to asbestos at work[24], Directive 2004/37/EC of the European Parliament and of the Council of 29 April 2004 on the protection of workers from the risks related to exposure to carcinogens or mutagens at work (Sixth individual Directive within the meaning of Article 16(1) of Council Directive 89/391/EEC) (codified version))[25].
A report on the role of OELs in the health and safety systems of 14 EU Member States found broadly comparable structures and systems for setting OELs in all member states and identified a variety of strategies undertaken in different countries to improve managing risks of working with hazardous chemicals. It was invariably made clear that OELs were not regarded as safe limits and they were frequently accompanied by recommendations to reduce exposures to as low as is possible below the limit. It was also noted that "Generally regulatory inspectorates rarely engage in proactive acts of monitoring compliance with specific OELs themselves. However, where there is concern over workplace airborne pollution that may be approaching or exceeding limits, there are requirements in some countries to inform and involve the regulatory agencies in monitoring. It is not clear how much this happens in practice"[26].
Relations between occupational exposure limits and derived no effect levels
Within the frame of the Community regulation on chemicals and their safe use (REACH), DNELs (Derived No Effect Levels) have been introduced in Europe. These represent levels of exposure above which humans (inclusive of consumers, workers, etc.) should not be exposed. Manufacturers and importers are required to calculate DNELs as part of their chemical safety assessment (CSA) for any chemicals used in quantities of 10 tonnes or more per year[27][28].
The DNEL is used in the risk characterisation part of the chemical safety assessment as a benchmark to determine adequate control for specified exposure scenarios. DNELs reflect the likely routes and duration and frequency of exposure. If more than one route of exposure is likely to occur (oral, dermal or inhalation), then a DNEL must be established for acute and repeated exposure, for each route of exposure and for the exposure from all routes combined. It may also be necessary to identify different DNELs for each relevant human population (e.g. workers, consumers or humans subject to exposure indirectly via the ambient environment), and possibly for certain vulnerable sub-populations (e.g. children, pregnant women)[29].
The starting point in establishing DNELs is a ‘No Observed Adverse Effect Level’ (NOAEL) or a ‘Lowest Observed Adverse Effect Level’ (LOAEL) from human data or animal studies[29]. The next step in the calculation of a DNEL is to address assessment factors extrapolating from experimental data to a real human exposure situation. This may result in a very conservative figure, perhaps two or three orders of magnitude lower than that from the traditional OEL setting process[12]. When an EU IOELV has been set, this may be applied as a DNEL for workers. Where an EU Binding Exposure Limit Value (BOELV) has been set taking into account socio-economic factors and technical feasibility, this cannot be used as a DNEL. Where a health-based national OEL has been set, the toxicological information used must be evaluated, and any differences to the REACH calculation must be taken into account[12].
The REACH regulation lays down general provisions for assessing substances and preparing chemical safety reports. For substances for which is not possible to determine a DNEL, a qualitative assessment should be carried out. In order to make this concept more precise, ECHA has developed the concept of Derived Minimal Effect Levels (DMEL) within the guidance document “Characterisation of dose [concentration]-response for human health”. A DMEL is a reference risk level considered to be of very low concern for a certain exposure scenario. It is not a level where no potential effects can be foreseen, it rather expresses an exposure level corresponding to a low, possibly theoretical risk. The starting point for DMEL derivation is the dose descriptor for the most critical effect. For non-threshold effects, the dose descriptor is usually derived from cohort or case-control studies reporting Relative Risks (RR) or comparable measures to describe a dose-response association. The RR is the ratio between the risk of the health effect in the exposed divided by the risk in the unexposed population. The next step in the derivation of a DMEL is to address variability and uncertainty in the differences between the population in the source data and the target population (i.e. the actual whole human population or those potentially exposed to the substance). The DMEL concept is still under debate[30].
