Plenary session of the MAK Commission 2023
Opportunities and limitations in the use of New Approach Methods for the assessment of substances / A total of 88 new publications in the year 2022
The DFG Senate approved the extension of the Commission’s mandate for a further six years in December 2022.
The plenary session of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) was held on 30 March 2023 in Berlin.
As reported last year, the issue of the so-called New Approach Methods (NAMs) is one that will increasingly influence the work of the Commission. With the aim of replacing animal experiments wherever feasible, these methods include data-based and simulation methods, and increasingly also development of cell-based high-throughput test systems. The opportunities and significance of these methods were summarised in a statement that was published immediately after the plenary session. In this statement, the Commission explains that the increasing use of NAMs makes an important contribution to the 3Rs principle and can substantially and meaningfully expand risk assessment when combined with conventional toxicological approaches. Before it is possible to dispense with animal experimentation for quantitative risk assessment as a prerequisite for the derivation of threshold limit values however, further research is required into the validation and scientific evaluation of the methodological possibilities and limitations of NAMs.
The reports issued by the Commission’s working groups have once again highlighted how important the specific perspectives of the individual working groups are when it comes to carrying out a comprehensive risk assessment of substances and describing the associated measurement methods. It is frequently possible to elucidate the mechanisms of action of substances by systematically engaging with issues such as percutaneous absorption, sensitisation, inhalation-related or carcinogenic aspects, and effects on the germ line. Understanding the mechanism of action is generally a prerequisite for the recommendation of threshold limit values. A further prerequisite is the availability of a sufficient number of studies that can be used for assessment purposes. At the level of the European Union, too, significant efforts are being undertaken to make existing toxicological data more readily available. Of particular importance in this context is the fact that the further development and validation of NAMs also depends on experimental findings obtained in animal models and in humans.
All working groups were additionally able to contribute to the Commission’s work through discussions and expert assessments relating to the development of scientific substantiations and methods, and to the Commission’s conceptual work. With the start of the new mandate period, leadership of the “Carcinogenesis” working group was transferred from Professor Dr. Michael Schwarz to Dr. Edgar Leibold. The Commission expressed its sincere thanks to Professor Schwarz for his leadership of the working group over many years. This working group also addresses the relevance of NAMs, with a particular focus on extrapolation procedures and AI-based approaches that aim to enable the transfer of in vitro findings to in vivo situations. The “Dusts” working group is concerned with the derivation of a MAK value for cerium dioxide, taking nanoparticles into account. The “Allergy” working group draws on the parallel availability of NAMs and data from human and animal models to further develop the integration of findings from both systems. In addition, work has begun on revising the criteria for respiratory allergens. The “Percutaneous Absorption” working group addressed the topic of penetration enhancement. Penetration enhancement can occur not only through unintentional contamination of the skin with substances of corresponding activity, but also as a result of deliberately applied skin products (disinfectants, protective and/or care products) or other substances (e.g. cleaning agents, water).
As usual, the derivation of all Commission findings was comprehensively documented and, following completion of the comment phases, published as open access for the research community and the public on the newly established platform supported by ZB MED (MAK Collection; link see below). Analyses indicate that the results are used nationally and to a significant extent also internationally. In order to ensure that the platform serves not only documentation purposes but also enables the reusability and compatibility of the results, the publications are prepared in such a way that user-oriented search functions can be applied and interoperability with other relevant databases is ensured.
In the past year, a total of 88 publications were produced, including 62 scientific substantiations, the derivation of 16 MAK and BAT values, and the description of 26 methods. This once again underlines the high level of voluntary commitment shown by the members and guests of the Commission. This level of output would not be possible without the support of the Commission’s Scientific Secretariat, however. It is only by drawing on the highly competent research and the draft texts prepared by the latter that it is possible to achieve such high quality in the first place. Particularly worthy of mention is the derivation of a MAK value for (ethylenedioxy)dimethanol, a biocide used in metalworking fluids. In addition, the MAK value for the solvent tetrahydrofuran was reviewed and its carcinogenicity classification was reassessed based on refined insights into the human relevance of tumour findings in animal studies. In view of the increasingly simple detection methods for the determination of foreign substances and their availability in many laboratories, the working group “Assessment Values in Biological Material” addressed, on a sound scientific basis, the requirements for suitable human biomonitoring parameters that can be used to assess the risk to workers when handling hazardous substances at the workplace. The resulting publication is due to come out this year.
The Commission observed a minute of silence in memory of its colleagues Dipl.-Ing. Karl-Heinz Schaller, Professor Dr. Ralf Stahlmann and Professor Dr. Thomas Gebel, who passed away recently. Not only their expertise and commitment to occupational health and safety were honoured, but also their outstanding personalities. They will be greatly missed. Over many years, they demonstrated impressive support for the work of the Commission.
In the coming year, the Commission will continue to work to ensure that risk-based assessment of substances based on scientific evidence remains the central foundation for regulatory decisions in occupational health and safety. In this context, particular importance is attached to the participation of the Chair of the Commission, Professor Dr. Andrea Hartwig, in the EU High-Level Roundtable on the Chemicals Strategy for Sustainability and in the Risk Assessment Committee (RAC) of the European Chemicals Agency (ECHA), and also the Commission’s cooperation with the Organisation for Economic Co-operation and Development (OECD).