A break-out session “Advancing risk assessment science: Human health” was held on September 19 and 20, 2018, at the 2018 conference of the European Food Safety Agency (EFSA) in Parma, Italy. The session addressed “advances, unresolved challenges, and needs for human health risk assessment,” and featured presentations on traditional toxicology and non-animal testing methods, as well as on epidemiological research.
Ellen Mantus of the U.S. National Academies of Science, Engineering and Medicine (NAS) presented and discussed several NAS reports, published in 2007, 2012, and 2017, that set the stage for risk assessment science of the 21st century. The latest report addressed “how data being generated today can be used in risk assessment applications” and discussed four potential application areas, namely “priority setting, chemical assessment, site-specific assessment and assessment of new chemicals.” One common challenge identified by this report was that “technology has evolved far faster than our ability to analyze, interpret and integrate [for risk assessment] the diverse, complex and large data streams” coming from exposure science, toxicology, and epidemiology. Mantus said that “a research agenda that develops, explores, and documents case studies that capture various scenarios of data availability for risk assessment applications will help to address the challenges,” and “multidisciplinary collaboration” will be absolutely critical to the success of this endeavor. As an example of another set of complex mechanisms that may need to be accounted for in risk assessment, Mantus highlighted the human microbiome and the effects it can have on chemicals and chemical toxicity. Research agenda for better understanding the significance of microbiome information for chemical risk assessments has been outlined in another NAS report (FPF reported).
Susanne Hougaard Bennekou of the Danish Environmental Protection Agency addressed the current compartmentalization of human health risk assessment and the need for a more holistic approach. As examples of such compartments, she highlighted the four steps of the risk assessment process and the fact that each substance is evaluated individually and separately within each regulatory silos. She then discussed a 2013 report commissioned by EFSA, which reviewed “epidemiological studies linking exposure to pesticides and health effects” and found “consistent increased risk” for several diseases. However, the multitude of potential confounding factors makes it difficult to confirm a causal link in an epidemiological study. In such a situation, plausible toxicity mechanisms could be investigated and confirmed in an animal model, but the problem is, for many human diseases of public relevance, animal models are not available. Thus, relevant data may still be missing among the various data provided to risk assessors with each pesticide submission. As a solution, Hougaard Bennekou suggested to develop innovative testing methods (including read-across) and strive for “integration of efforts” in looking “at the bigger picture.” She further added that more attention should be given to negative results data, which are neglected currently. Commenting on the call for more data transparency, she warned that, before “dumping all these pdf files” onto open public, regulators need to “first make better use of their data themselves.”
Thorhallur Halldorsson of the University of Iceland discussed the strengths and limitations of epidemiological studies in the context of chemical risk assessment. He pointed out that epidemiological studies have the potential to deliver human-relevant observations not possible with animal models, and this could help to reduce uncertainty in risk assessment. However, human studies are more complicated than studies in animals due to confounding bias, co-exposures, lack of unexposed individuals, and high variability in lifestyle factors. Study design and especially the quality of the exposure assessment are crucial in determining the usefulness of an epidemiological study for risk assessment.
CLARITY-BPA research (FPF reported) was addressed in two presentations by Barry Delclos of the U.S. Food and Drug Administration (FDA) who talked about the results of the regulatory study (FPF reported) and Nigel Walker of the U.S. National Toxicology Program (NTP) who discussed NTP’s experiences with “integrating regulatory and academic investigations” (FPF reported). Walker confirmed that, in addition to the two separate reports detailing the outcomes of the regulatory study (FPF reported) and academic studies (FPF reported), there will be a third report, which will integrate the results of the two.
EFSA (2018). “Advancing risk assessment science: Human health.” Break-out session
EFSA (September 20, 2018). “Science, food, society: EFSA conference 2018 – day 3.”
Ntzani, E., et al. (2013). “Literature review on epidemiological studies linking exposure to pesticides and health effects.” EFSA supporting publication 2013:EN-497