Integrating evidence – the demanding analysis and integration of study results for the derivation of threshold limit values / A total of 96 new publications in 2023

The members, permanent guests and invited guests of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) met in Berlin on 20 March 2024 for this year’s plenary session.

The Commission’s work has always focused on the scientific recommendation of threshold limit values for substances relevant to the workplace. This work is based on the analysis and integration of all available information, findings and studies relating to a given substance. A key challenge in this context is the generally insufficient data available from studies conducted on humans 1(externer Link). As a consequence, the derivation of threshold limit values often requires the integration of findings obtained in different animal models and thus across different species, and the alignment of this information with available human data. This interspecies correlation requires collaboration between different scientific disciplines and is highly demanding. Further insights come from studies on the substance’s mode of action, such as those carried out in cell cultures. In recent years, numerous alternative approaches to substance assessment have also been developed. In 2022, the Commission set out its position on the opportunities and limitations of these so-called New Approach Methods (NAMs), which include in particular data-based and AI-based simulation approaches as well as high-throughput test systems 2(externer Link). Accordingly, the past working year saw the continuous expansion of the Commission’s expertise, intensive engagement with these new methods, and the development of concepts for integrating findings from conventional toxicological studies with those obtained using alternative approaches. This included an exchange with Professor Thomas Hartung of Johns Hopkins University, a recognised expert in organoid cultures and AI-based approaches in toxicological research. 

In the reports issued by the Commission’s working groups presented at the plenary session, it once again became impressively clear how the specific focal points of the individual working groups interlock and contribute equally to risk assessment and the establishment of measurement methods. Through engagement with issues such as percutaneous absorption, sensitisation, inhalation-related or carcinogenic effects, and possible effects on the germ line, each of which is examined within the respective working group, it is often possible to elucidate the toxicological effect profiles of substances. Understanding the mechanism of action is generally a prerequisite for a sound risk assessment and the starting point for effective protective measures.

In the past year, a total of 96 publications were produced, including 43 MAK and 25 BAT scientific substantiations, the derivation of 11 MAK and 5 BAT values, and the description of 14 methods for air analysis and 14 methods for biomonitoring. This large number of publications once again highlights the high level of voluntary commitment on the part of all those involved in the Commission’s work. At the heart of the Commission’s capacity to function is its Scientific Secretariat: its highly competent research activities and the discussion papers it prepares form the basis for both the productivity and the quality of the Commission’s work. Looking back on the past year, several particularly complex assessments can be highlighted. Bisphenol A, a substance widely known to the public as a plasticiser in plastic products with hormone-like effects, is suspected of posing a significant health risk. Here, extensive new studies were reviewed and their quality assessed; work on this topic is not yet complete. In addition, numerous new studies on aluminium were screened, leading to the conclusion that the MAK value must be reviewed. Furthermore, a proposal for a threshold limit value was developed for cerium dioxide, a substance used in catalysts as well as in grinding and polishing agents. Taking graphene as an example – a component of nanoelectronic and photonic devices – toxicological effects are currently being discussed based on specific material properties. Existing epidemiological studies and animal experiments were consulted in the assessment of glass wool, and a threshold limit value was derived which takes into account the mixing ratios of dust and fibres encountered in practice. Looking ahead, substances used in the production and application of renewable energy technologies are increasingly moving into the focus of the Commission’s work.

The success of the Commission’s work is reflected in the fact that, with the exception of one threshold limit value, all of its recommendations have been incorporated into statutory regulations.

Following completion of the comment phases, the results of the Commission’s work were again made available in open access to the research community and the public last year on the platform established by ZB MED, the “MAK Collection”, both as the List of MAK and BAT Values and as the journal “The MAK Collection for Occupational Health and Safety”. In addition, the opportunity was taken in the course of the past year to further raise awareness of the Commission’s work at various academic conferences in Germany and abroad.

At the European level, the Commission continued to advocate for risk-based assessment of substances as the central foundation for regulatory decisions in occupational health and safety. This is against the backdrop of a European discourse that currently places increasing emphasis on the avoidance and banning of substances. From the Commission’s perspective, however, quantitative risk assessment of chemicals remains a far more realistic and appropriate strategy for protecting the population, particularly at the workplace. This is all the more relevant given that the production and use of renewable energies inherently require the safe handling of the substances involved. In terms of contributing this perspective to the broader debate, valuable opportunities are provided by 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), as well as by the Commission’s cooperation with the Organisation for Economic Co-operation and Development (OECD). In a broader sense, this also includes the current discourse on a roadmap towards phasing out animal experimentation in chemicals testing. Here, too, the Commission seeks to contribute the perspective of research through dialogue and cooperation with other science stakeholders, including the Permanent Senate Commission on Animal Research.

Further information:

• Commission homepage(interner Link)
• MAK Collection(externer Link)
• List of MAK and BAT Values(externer Link)

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¹ Relevanz von Humanstudien für die Ableitung von Arbeitsplatzgrenzwerten (in German only)(Download) - Positionierung der Ständigen Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe [Relevance of human studies for the derivation of occupational exposure limits – Position paper issued by the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area] (2019)

² New Approach Methods (NAMs) in der wissenschaftsbasierten Abteilung von Grenzwerten - derzeitige und zukünftige Rolle (in German only)(Download) - Stellungnahme der Ständigen Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe [New Approach Methods (NAMs) in the science-based derivation of threshold limit values – current and future roles – Position paper issued by the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area] (2023)