Assessing and regulating of chemical mixtures under REACH

Chemicals are usually mixed with other chemicals for further processing in formulations (e.g. paints and varnishes) or articles (e.g. car tyres). During their life cycle (i.e. during manufacture, use, or disposal), they can enter the environment via different pathways where other chemicals are already present. There are different levels of complexity (see Figure 1): while individual chemicals are relatively easy to identify or define, this is not the case for mixtures. A distinction can be made between intentional and unintentional mixtures.

Intentional mixtures occur when chemicals are combined for a specific purpose, e.g. in formulations such as paints or varnishes. The composition of intentional mixtures is known at least to the formulating manufacturer.

Unintentional mixtures occur when chemicals are released and cooccur in wastewater treatment plants or environmental media (e.g. rivers). Their composition is mostly unknown and complex.

Figure 1

Simplified scheme of the different levels and complexity of mixtures (Source: Hassold et al. 2021)

Source: Enken Hassold et al. 2021 / UBA

Since chemicals are usually further processed in mixtures or products, they rarely occur as individual chemicals. In particular monitoring data show that chemicals do not occur individually in the environment, but are present in complex mixtures, entering from various sources.

It is also known that chemicals produce joint effects. This is described by the term combined effect or joint effect. For example, laboratory studies demonstrated that chemicals in mixtures can cause significant measurable effects in organisms, even though each individual chemical was present in the test mixture at concentrations below "safe" limits. Therefore, chemicals cannot be simply considered in isolation when assessing their risk.

In order to describe the joint effects and predict mixture toxicity based on the toxicity of individual chemicals, two different concepts, have been established, which rely on different underlying assumptions: Concentration Addition and Independent Action. Both concepts assume additive joint effects without interaction between the individual chemicals. The concept Concentration Additions has been accepted as pragmatic and feasible tool to predict mixture toxicity, because it calculates with available data (effect concentrations such as EC50). In addition, predictions are often more conservative and hence more protective for the environment.

Both concepts assume that no interactions take place between the chemicals, i.e. they do not influence each other in their mode of action. Interactions can occur, for example, when a substance promotes the uptake of another substance in the organism causing stronger effects or when effects cancel each other out. If the effect is stronger and more than "additive", we speak of "synergism", if it is less than predicted and weakens, we speak of "antagonism". But such interactions are rare.

There is evidence that the risks to the environment from the co-occurrence and joint effects of chemicals are currently underestimated in many cases. In order to assess chemical mixtures using the two existing concepts (see above), data on composition, exposure and effect concentrations of the components are needed. When these data are available, a risk assessment can be made for well-defined mixtures. The concepts have been reviewed and applied in many scientific studies and have also found their way into regulatory practice, i.e. they are already used in the context of various regulations and integrated into risk assessment concepts.

Under the European REACH (Regulation (EC 1907/2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals), the risks of individual chemicals are assessed and environmental concentrations are derived for registered chemicals, that are considered safe. While companies are responsible for the chemical safety assessment of all chemicals, authorities can take targeted measures in certain cases. REACH is a single substance regulation (Figure 2).

Figure 2: REACH companies (registrants) evaluate their individual substances (Source: Hassold, Aust, Juffernholz, Leitner: "Chemical Mixtures & REACH: A starting point", SETAC GLB Landau 2011)

There are currently no explicit legal requirements under REACH to address possible additional risks arising from chemical mixtures. REACH only makes the general requirement that the safe use of chemicals as such in mixtures and in articles should be ensured. At this point, REACH has regulatory gaps, as the co-occurrence and joint effects of several substances are not explicitly mentioned and the implementation of this requirement is unclear. There is no specific assessment of the potential risks from intentional or unintentional mixtures. Intentional mixtures are currently only considered in the context of classification and labelling of chemicals. This involves evaluating whether components of the mixture are classified as hazardous and thus whether the mixture is also to be classified as hazardous.

Figure 2

REACH companies (registrants) evaluate their individual substances

Source: Hassold, Aust, Juffernholz, Leitner: Chemical Mixtures & REACH: A starting point, SETAC GLB Landau 2011

Figure 3: A) One substance from several sources, uses, e.g. products from different manufacturers (aggregated exposure); B) One registrant assesses several substances in a mixture; C) Mixture assessment: combined exposure and effect of different substances from different sources are taken into account. D) REACH could consider exposure of existing substances from other sources outside REACH (pharmaceuticals, biocides or pesticides). (Source: Hassold, Aust, Juffernholz, Leitner: "Chemical Mixtures & REACH: A starting point", SETAC GLB Landau 2011)

There are various approaches to move away from the current single substance assessment towards a better consideration of intentional and unintentional mixtures. UBA has evaluated these in several research projects.

A first step towards an improved assessment of chemicals is to take into account the release of a single chemical from several uses over the entire life cycle, the so-called aggregated exposure. A research project funded by the German Enviornemnat Agency (UBA) made several proposals for determining the aggregate total concentration of a substance in the environment (Groß et al. 2011).

The composition of intentional mixtures is theoretically known to the user. In practice, however, information on the composition and properties of chemicals is often not shared along the complete supply chain and with all actors. Also, data on the release of the chemicals is very rarely available in a transparent way. In order to improve the communication of data for intentional mixtures along the supply chain, the industry associations VCI (German Chemical Industry Association) and CEFIC (European Chemical Industry Council) have proposed the so-called LCID (Lead Substance Identification) method and SUMI (Safe Use of Mixtures Information) (CEFIC 2016). The German Environment Agency sees opportunities for improving the assessment of mixtures (Reihlen et al. 2012, Galert & Hassold 2021).

The possibilities for addressing unintentional mixtures were investigated in a research project initiated by UBA (Bunke et al. 2014). Specific assessments using existing concepts are theoretically possible for known and definable mixtures with sufficient data. This includes the prediction of mixture toxicity or a risk characterisation via summation of the individual risk quotients. The main challenges are the availability and communication of data on effects, exposure and the composition of complex mixtures. Furthermore, the responsibilities, tasks and information situation of the different actors vary (see Figure 4). This complicates the assessment of chemical mixtures by the registrant or user.

Figure 4: Simplified representation of the information availability for the different actors for the possible assessment of mixtures (source: Hassold et al. 2021).

Ultimately, all cooccurring substances falling under different regulation in the environment would have to be taken into account in the environmental assessment and, in addition to REACH chemicals, background contamination from pesticides, pharmaceuticals or biocides would also have to be considered.

Figure 3

A) One substance from several sources, uses, e.g. products from different manufacturers (aggregated exposure); B) One registrant assesses several substances in a mixture; C) Mixture assessment: combined exposure and effect of different substances from different sources are taken into account. D) REACH could consider exposure of existing substances from other sources outside REACH (pharmaceuticals, biocides or pesticides).

Source: Hassold, Aust, Juffernholz, Leitner: Chemical Mixtures & REACH: A starting point, SETAC GLB Landau 2011

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Figure 4

Simplified representation of the information availability for the different actors for the possible assessment of mixtures

Source: Enken Hassold et al. 2021 / UBA

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The assessment of mixtures is complex. Due to the large number of possible combinations, a close prioritisation and good data situation would be required to identify the mixtures with relevant risks in order to then assess them. Assessments can be carried out by the companies on the one hand, but also by the authorities if necessary. UBA has elaborated basic proposals on possible approaches on the assessment of mixtures under REACH and their challenges (Hassold et al. 2021). These are outlined in Figure 5.

Figure 5: Schematic representation for a possible evaluation of mixtures by registrants, formulators or authorities (Source: Hassold et al. 2021)

Improved data on emissions and environmental occurrence of substance combinations and ecotoxicological effects, as well as their availability in databases for different actors, is a crucial basis for all mixture assessments.

The environmental risks of intentional mixtures should be assessed by companies (registrants and users) to ensure their safe use. For this purpose, existing methods & tools of industry associations (such as "LCID" and "SUMI", see above) should be improved. Instead of considering only one lead substance, these should consider the joint effects and exposures of several chemicals.

It is up to the authorities to make targeted assessments or take regulatory measures for chemicals in justified cases to address environmental risks. This would include environmental risks from unintentional mixtures or well-defined groups of substances. However, this is very laborious and dependent on available data for well-defined mixtures.

The communication of data needed to account for unintentional mixtures of REACH chemicals from different entry pathways is extremely complex. As a result, relevant data are often not available and specific assessments of unintentional mixtures are only possible in individual cases. Therefore, a generic consideration of mixtures with the help of defined factors or upper limits (mixture allocation factor "MAF") within the framework of the single substance assessment is discussed as a possibility to reflect the co-occurrence and joint effects in the environmental risk assessment. In the context of the European Green Deal (EU COM 2019) and the Chemicals Strategy for Sustainability (EU COM 2020, EU COM SWD), the EU Commission plans to develop a proposal for a mixture allocation factor (MAF) under REACH by the end of 2022 in order to generically address possible risks from mixtures. Together with other national and European authorities, the German Environment Agency is supporting the development of methods for the risk assessment of mixtures (e.g. the MAF) so that they can be better regulated in the future.

Figure 5

Schematic representation for a possible evaluation of mixtures by registrants, formulators or authorities

Source: Enken Hassold et al. 2021 / UBA

The text was prepared on the basis of the publications listed below. Further references can be found in the publications mentioned.

An overview of research projects and publications can also be found here.

Research projects by UBA

• Groß, R., Bunke, D., Gartiser, S. (2011): Basic principles for the development of a concept for environmental exposure assessments of single substances released from multiple uses under REACH, Project No. (FKZ) 360 01 058. Umweltbundesamt, Dessau-Rosslau; https://www.umweltbundesamt.de/en/publikationen/basic-principles-for-development-of-a-concept-for
• Reihlen, A., Jepsen, D., Wirth, O. (2012): Consolidation of Information for Mixtures under REACH – Analysis of the DPD+ Method; Project No. FKZ 3710 63 403 Umweltbundesamt, Dessau-Rosslau. Final Report Part I (Analysis Report) available via: http://www.reach-hamburg.de/fileadmin/user_upload/dokumentationen/Materialien/4_5_3_Kommunikation_in_der_Lieferkette/120508_Mixtures_under_REACH_v3.pdf; Executive summary available via http://www.reach-hamburg.de/fileadmin/user_upload/dokumentationen/Materialien/4_5_3_Kommunikation_in_der_Lieferkette/120430_Mixtures_under_REACH_Exec_Summary.pdf
• Dirk Bunke, Rita Groß, Fritz Kalberlah, Jan Oltmanns, Markus Schwarz, Antonia Reihlen, Ninja Reineke (2014): Mixtures in the Environment – Development of Assessment Strategies for the Regulation of Chemicals under REACH; Ed. Enken Hassold, Nannett Aust; Texte 65/2014, 08/2014; Umweltbundesamt; FKZ 3711 63 429; https://www.umweltbundesamt.de/en/publikationen/mixtures-in-the-environment-development-of
• Anja Coors, Pia Vollmar, Frank Sacher, Astrid Thoma, Dirk Maletzki, Christian Polleichtner, Patrick Schwarz (2017): Joint effects of pharmaceuticals and chemicals regulated under REACH in wastewater treatment plant effluents – Evaluating concepts for a risk assessment by means of experimental scenarios; Ed. Daniela Gildemeister, Ute Kühnen, Enken Hassold; Texte 61/2017, August 2017; Umweltbundesamt; FKZ 3712 64 419; https://www.umweltbundesamt.de/en/publikationen/joint-effects-of-pharmaceuticals-chemicals

Publications by UBA

• Hassold, Galert, Schulze (2021): Options for an environmental risk assessment of chemical mixtures under REACH - the status and ways forward; Environmental Sciences Europe 33:131. https://doi.org/10.1186/s12302-021-00565-0
• Galert W, Hassold E. (2021). Environmental risk assessment of technical mixtures under the European REACH regulation – a regulatory perspective. Integrated Environmental Assessment and Management 17 (3): 498-506. DOI: 10.1002/ieam.4393
• Coors, Anja, Pia Vollmar, Frank Sacher, Christian Polleichtner, Enken Hassold, Daniela Gildemeister, Ute Kühnen (2018): Prospective environmental risk assessment of mixtures in wastewater treatment plant effluents – theoretical considerations and experimental verification; Water Research 140: 56-66
• Hassold, E., Drost, W., Juffernolz, T., Aust, N. (2010): Berücksichtigung von Chemikalien-Mischungen bei der Umweltrisikobewertung; Umwelt und Mensch Informationsdienst (UMID) 4: 39-42

Other sources

• Commission (2019) Communication from the commission to the European parliament, the European council, the council, the European economic and social committee and the committee of the regions. The European Green Deal. European Commission. COM (2019) 640 final.
• Commission (2020). Progress report on the assessment and management of combined exposures to multiple chemicals (chemical mixtures) and associated risks (staff working document accompanying the communication of the commission on the "chemicals strategy for sustainability towards a toxic-free environment"). European commission. SWD(2020) 250 final
• Commission (2020). Communication From The Commission To The European Parliament, The Council, The European Economic And Social Committee And The Committee Of The Regions. Chemicals Strategy for Sustainability. 14.10.2020. COM(2020) 667 final
• CEFIC (2016). Reach practical guide on safe use information for mixtures under reach - the lead component identification (lcid) methodology. Final version 6.1 – 25 february 2016. Created by the european chemical industry council (cefic) and vci (verband der chemischen industrie e.V.) as a contribution to the csr/es roadmap (action 4.4a; http://echa.Europa.Eu/regulations/reach/registration/informationrequirements/chemical-safety-report/csr-es-roadmap
  http://echa.Europa.Eu/regulations/reach/registration/informationrequirements/chemical-safety-report/csr-es-roadmap