In a scientific review published on May 20, 2016, in the peer-reviewed journal Regulatory Toxicology and Pharmacology, Aude Kienzler and colleagues from the Institute for Health and Consumer Protection, Joint Research Centre (JRC) of the European Commission (EC), review the approaches to risk assessment (RA) of chemical mixtures currently used in the European Union (EU) and the U.S.. In addition, recent case studies of RA for mixtures were reviewed, drawing from approaches based on chemical class or specific matrix, such as water or air.

It was found that most of the current RA requirements in the EU are focused on single chemicals and specific sectors of use. Apart from RA of intentional mixtures in formulated products, no clear requirements or guidance for RA of mixtures are in place, although the importance of mixture effects is recognized by several pieces of legislation. There are also no clear requirements for mixture assessment across various regulatory frameworks, despite the importance of this approach for calculating the aggregate exposure. Further, several case studies were reviewed, highlighting data gaps as a most important impediment to the RA of chemical mixtures.

The article also summarizes the results of the JRC-conducted expert survey on approaches to RA of mixtures (FPF reported). Fifty-eight experts from 21 countries participated in the survey, with most experience gained in the area of plant protection products and REACH. The experts generally agreed that the novel tools, e.g. in vitro methods, omics, read-across, TTC approaches or adverse outcome pathways (AOPs), could be of value in the RA of mixtures. These tools could enhance the understanding of the mechanisms resulting in combined effects. However, most of the experts also noted that the use of these tools is “currently limited because of a lack of guidance, lack of data, or lack of expertise.”

The authors conclude that, despite the availability of several recently developed frameworks for RA of chemical mixtures, and a host of novel tools which may offer further improvements, there is currently “a need to build on all these frameworks to develop a robust and transparent approach not only for conducting, but also reporting a chemical mixture RA.”


Kienzler, A., et al. (2016). “Regulatory assessment of chemical mixtures: Requirements, current approaches and future perspectives.Regulatory Toxicology and Pharmacology (published online May 20, 2016)