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Epigenetics not yet ready for risk assessment

Science - chromosomes

Epigenetics data are not yet ready for regulatory risk assessment, according to expert discussions at a scientific conference in Valencia, organised by Efsa.

Hubert Noteborn from the Netherlands Food and Consumer Product Safety Authority chaired the colloquium on epigenetics and risk assessment on 14-15 June. "The main messages that I took away from the scientific colloquium are that although there is evidence, it is not yet possible to predict adverse effects from epigenetic changes,” he told Chemical Watch.

“Human data may suggest a causative effect, but it's necessary to demonstrate causality in experimental models. Greater mechanistic understanding of epigenetic changes is required to develop in vitro and in vivo assays,” he added.

The conference aimed to identify cross-cutting issues, existing data gaps and research needs, as well as to address methods for investigating epigenetic effects in vitro and in vivo. “It is remarkable that, for instance, in cancer and occupational health risk assessment, we observe a shift over the last decades towards 'genetic and epigenetic factors that may be a major cause of variability in response in similarly exposed individuals',” Dr Noteborn told Chemical Watch, quoting from a 2015 journal article. As such, Efsa's scientific committee has identified “individual susceptibility” as a priority topic for new risk assessment guidance.

At the meeting, Daniel Doerge from the US FDA described work on furan, a widely studied suspected carcinogen found in a range of food items, from coffee to cereal. His team at the National Centre for Toxicological Research has been looking for concordant changes in gene expression and epigenetic endpoints, such as DNA methylation and histone modification, at different furan exposures.

At this stage, epigenetic studies are most useful for “mechanistic interpretation of pathways and specific genes”, he said.

“I guess I'd argue that epigenetic effects are subject to the same uncertainty as all of the other effects that we look at,” he said. Separating specific effects from general cell damage caused by chemicals such as furan is “really difficult”, he added.

Kevin Chipman from Birmingham University spoke of his interest in using epigenetics data for a “retrospective reflection” of exposure to environmental stressors. He referred to identical twins who have far greater epigenetic differences at age 50 than at age 3, showing that the changes build up over a lifetime. “Can we use changes in the epigenome retrospectively as a footprint (memory) of previous exposures?” he asked.

Participants, at the meeting, split into four discussion groups:

  • incorporating epigenetics data in mode of action and adverse outcome pathway frameworks;
  • epigenetics and chemical risk assessment in humans;
  • epigenetics in risk assessment of farmed animals for food production; and
  • epigenetics and environmental risk assessment.

Summing up, all groups agreed that data gaps need to be filled, before epigenetics data can be used in a regulatory setting. 

There is a need for a “better understanding” of epigenomics, which involves developing and validating testing models, said Sandra Ceccatelli from the Karolinska Institute in Sweden, who provided the meeting's take home messages and questions. To help understand what epigenetic modifications actually mean, they should be anchored to a phenotype (physical characteristics) and gene expression alterations, she suggested.

“More translational science is necessary in all fields considered at this meeting,” she concluded.

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