MAK Values Working Group
The “MAK Values and Classifications” Working Group develops and reviews science-driven proposals for threshold limit values in the air at the workplace; conceptual work is also incorporated on an ongoing basis.
Proposals are presented on the classification and labelling of peak limits, carcinogenicity, germ cell mutagenicity, sensitising effect, contribution of skin absorption to systemic toxicity and potential additional risk during pregnancy; these are discussed and approved in the “MAK Values and Classifications” Working Group. More detailed descriptions of the Commission’s approach to evaluating these endpoints can be found in the relevant sections of the List of MAK and BAT Values. Specific groups of substances are also considered in working groups, including lubricants, dusts and nanomaterials as well as metals and their compounds. Conceptual work that is pursued in specific working groups and incorporated in the work of the “MAK Values and Classifications” Working Group includes the extrapolation of animal test data to humans as well as concepts for the inclusion of early, sensitive parameters for the prevention of neurotoxicity and chronic inflammation, for example.
BAT Values Working Group
The “Assessment Values in Biological Material” (BAT Values) Working Group develops concepts and assessment values for the use of biomonitoring in occupational medicine.
The following are evaluated and re-evaluated:
- Biological work substance tolerance values (BAT values),
- Biological guidance values (BLW),
- Exposure equivalents for carcinogenic agents (EKA), and
- Biological work substance reference values (BAR).
For substances where no appropriate value can be derived based on the available studies and after discussion, documentation is drawn up on the current data situation.
The BAT value derived as a health-oriented mean value is designed to protect the health of an employee even in the event of repeated and long-term exposure. In collaboration with the Developmental Toxicity Working Group, the BAT values are systematically examined and an attempt is made to derive a concentration in biological material for work substances of pregnancy group B for which a teratogenic effect cannot be assumed. The exposure equivalents for carcinogenic work substances (EKA) and the biological guidance value (BLW) are important medical guidelines for the biological monitoring of carcinogenic work substances. The EKA allow the derivation of substance-specific equivalent values in biological material according to the acceptance and tolerance concentrations established in the Exposure-Risk Relationships (ERB) of the Committee on Hazardous Substances (AGS), whereby extrapolation into the low-dose range and competing sources are discussed critically for each specific substance. Additional occupational exposure can be estimated for the population at large based on the biological work substance reference values (BAR).
The concepts and assessment values are continuously reviewed by the working group and made transparent by means of ongoing publication of the scientific documentation and justifications in German and English in “The MAK Collection for Occupational Health and Safety”.
The “Assessment Values in Biological Material (BAT Values)” Working Group, together with the “Biomonitoring” Working Group, established the science-based prerequisites for the implementation of biomonitoring.
Biomonitoring Working Group
The “Biomonitoring” Working Group develops, tests and publishes analytical methods that can be used to determine harmful substances in the work area, their metabolites and characteristic parameters of intermediate metabolism in human biological materials. The quantification of these substances and/or parameters is the basis of the method used in occupational medicine and environmental medicine known as “biomonitoring” or “human biomonitoring”, which seeks to achieve early detection of potential health risks. Due to its importance in terms of individual prevention, biomonitoring is also anchored in the relevant directives in legislation and the principles of the professional associations.
The notable feature of the procedures published by the working group is that they have been tested for their analytical reliability and reproducibility. So as to be able to obtain sound information on the reliability of an analytical method, a thorough examination is carried out by means of reproduction in at least one independent working group. In order to ensure this, the working group consists of experts who have the necessary experience in developing and validating biomonitoring procedures and are able to follow up and check externally prepared procedures in their laboratories.
In addition to providing reliable biomonitoring methods for occupational health practice, the testing and evaluation of methods for biological analysis is extremely important in terms of assessing occupational health studies used to determine MAK and BAT values.
Air Analyses Working Group
The “Air Analyses” Working Group is made up of chemists and engineers from universities, research institutes, industrial companies and authorities.
The aim of this working group is to develop validated analytical methods in cooperation with the Commission’s “MAK Values” Working Group and with other national and international bodies for hazardous substances in the air at the workplace, drawing on specialist literature and the expertise of its members.
The methods are tested for their practical suitability by another laboratory before they are published within the working group.
Since its existence, the working group has not only successfully implemented this concept but has also introduced method testing by means of a plausibility check in case experimental testing by a second laboratory is not possible due to a lack of available capacity.
Developmental Toxicity Working Group
The “Developmental Toxicity” Working Group evaluates the substances in question in terms of whether exposure at the workplace to germ cells or during pregnancy has a harmful effect on the development of an unborn child.
Inflammation Working Group
Inflammatory reactions are caused by many different hazardous substances at the workplace. Chronic inflammation is considered to be the cause of carcinogenesis and also of fibrosis, for example as a result of long-term and comparatively high concentrations of fine and ultra-fine dusts, even without further chemical reactivity (so-called GBS), resulting in chronic lung overload. On the other hand, inflammatory processes also perform important physiological functions, such as wound healing.
In order to prevent the above-mentioned chronic diseases in humans, a MAK Commission working group looks into the question of which parameters can be used to identify the inflammatory effects of workplace-related hazardous substances as early as possible in order to establish general criteria for estimation and evaluation. Key questions here relate to the differentiation between inverse inflammatory processes and physiological reactions, the transition from acute to chronic inflammation taking into account the reversibility of the effects, and also comparing the specific parameters for the assessment of potential qualitative and quantitative differences between such reactions in experimental animals and human beings. Appropriate measurement parameters as well as morphological and functional correlations are identified which can be obtained in both animal and human tests, for example by conducting clinical trials.
Epidemiology and Statistics Working Group
The definition of threshold limit values for substances in the work area is based on toxicology and epidemiology data. Major epidemiological study types include case-control studies and cohort studies with good data on exposure, health endpoints and potentially competing risk factors. This working group, which was founded in autumn 2020, will focus on the possibilities and limitations of epidemiological and statistical procedures in the low dose range.
Allergy Working Group
In the “Allergy” Working Group, work substances are evaluated with regard to a (photo)sensitizing/allergenic effect after skin contact and/or inhalation. The working group is made up of occupational health professionals, dermatologists, and toxicologists.
Percutaneous Absorption Working Group
The “Skin Absorption” Working Group carries out research and evaluates the current state of knowledge relating to the percutaneous absorption (skin absorption) of dangerous substances; it follows the MAK Commission in its selection of substances. The working group provides a substantiation for the allocation of “H-statements” based on hierarchically graded toxicological criteria (human data, animal experimental data, in vitro data, model calculations) in the List of MAK and BAT Values published by the Senate Commission.
Priority is given to the results of experimental studies or case studies. If these do not yield any relevant findings, mathematical models are used to estimate the dermal flux. Quantitative evaluation of the studies or model calculations is carried out according to the criteria for the allocation of H-statements (MAK Collection for Occupational Health and Safety, Vol. 2 Issue 3, p. 1112-1118). In addition, the working group deals with general scientific topics relating to the skin absorption of hazardous substances.
Carcinogenesis Working Group
The task of the MAK Commission’s “Carcinogenesis” Working Group is to evaluate substances in the work area in terms of their carcinogenic potential. The focus is on investigating the mechanisms underlying carcinogenic effects and the resulting risk assessment for human beings. All available information is used for evaluation purposes – human observations, epidemiological studies, animal studies and in vitro studies, and toxicological databases are also consulted. The general principles that inform classification of carcinogenic substances in the work area in different categories according to their effect mechanism and potency are listed in Section III of the List of MAK and BAT Values.
Another important task of the working group is the development or advancement of conceptual procedures. Even if a case-by-case study is ultimately necessary, this longer-term work serves to develop or refine the general decision-making criteria. Among other things, this includes the question of how certain tumours produced in animal experiments can be assessed in terms of their significance for human beings. For this purpose, a mechanistic understanding of the development of these tumour forms is crucial: one issue that arises here is the extent to which results from in vitro studies, e.g. from the US Tox21/ToxCast program, can be incorporated in decisions. Furthermore, inclusion of the effect mechanism also serves to assess whether health-based threshold limit values can also be proposed for carcinogenic substances in the work area. This applies in particular to non-genotoxic carcinogens (carcinogenicity category 4). However, differentiated evaluation criteria are also developed for predominantly genotoxic substances, which include the background levels caused by metabolic processes.
Lubricants Working Group
The “Evaluation of Lubricants” Working Group is made up of dermatologists, toxicologists and occupational health professionals and is dedicated to the evaluation of cooling lubricants, hydraulic fluid components and other lubricants.
In particular, exposure to cooling lubricants (definition: lubricants in liquid form) is a special area of occupational medicine and toxicology: it involves the use of a complex mixture of components, the aerosolisation of the cooling lubricant and frequently unavoidable direct skin contact.
Metals Working Group
Metals and metal compounds are widely used at the workplace. However, many metals and their compounds have been shown to be carcinogenic in humans and/or animals and have been classified according to the appropriate carcinogenicity categories. Other critical endpoints include pronounced inflammatory reactions and potential neurotoxic effects after inhalation. Here too, evaluation concepts have an important role to play.
In the absence of sufficient epidemiological and toxicological data for each metal compound, the Commission has, for example, developed approaches for examining the joint classification of different metal species based on effect mechanisms and including the criterion of bioavailability. In addition, consideration is given to the question of whether the effect mechanism for some carcinogenic metal compounds can be used to allocate them to carcinogenicity category 4 and whether it is possible to derive a MAK and/or BAT value from this.
Nanomaterials Working Group
Nanomaterials are becoming increasingly important in a wide range of applications. A prerequisite for the acceptance of this key technology is the safe handling of the respective materials, however, and this requires a well-founded risk assessment. Potential toxic effects depend not only on the chemical composition of the materials but also on the structure and surface properties of the particulate or fibrous nanomaterials.
Since it is not possible to consider each material separately, whether now or in the future, a working group establishes evaluation concepts for groups of nanomaterials and defines areas where research is required in this field. A summary of the state of science at the time was published in a DFG brochure in 2013. Based on the results of a long-term study using animal experiments with ceric oxide and barium sulphate, concepts regarding the effect mechanisms and possible groupings are currently being refined and the consequences for threshold limit values are being discussed.
Neurotoxicity and Chemosensation Working Group
Many substances in the workplace trigger harmful effects on health through interactions with the peripheral (sensory) or central nervous system (neurotoxicity). The enormous expansion of knowledge in the neurosciences now enables the mechanisms and health effects of substances on the nervous system to be measured more accurately so that their relevance to health can be evaluated more effectively. The working group evaluates current scientific developments (e.g. imaging methods, biomarkers) and their use in scientific studies on neurotoxic working materials.
Here, it is of particular interest to link the neurotoxic mechanisms triggered by substances in the work area to behavioural effects (e.g. memory or attention deficits). In this way, neurobiological knowledge can support the plausibility of the cognitive deficits observed. Another focus is on evaluating local irritant effects and limiting exposure peaks. In humans, these irritations are based on sensory irritations, and the working group tests the human data available for this substance group so as to be able to make recommendations for avoiding acute sensory irritations.
Dusts Working Group
The task of the “Setting Threshold Limit Values for Dusts” Working Group is to derive threshold limit values for dusts and dust-like hazardous substances at the workplace. Dust pollution at the workplace affects a very large number of workers in Germany, estimated at around 6 million. This is why the control of dust exposure is not only important in terms of the health of individual employees but also a key issue for the economy as a whole.
General principles relating to the definition, properties and effects of dusts and aerosols are listed in Section V of the List of MAK and BAT Values.