News Q&A: Shedding new light on pesticide-disease linkages

Scientists rely on experimental toxicology evidence, such as animal or cell studies, to assess their safety.

A new approach proposed by the European Food Safety Authority (EFSA) makes better use of epidemiological studies on human health.

Human epidemiological studies have suggested an association between exposure to certain chemicals and human diseases. However, an association does not necessarily prove a cause-and-effect link, so firm conclusions cannot easily be drawn from epidemiological studies.

EFSA’s pesticide experts have been exploring how results from epidemiological studies can be integrated into pesticide risk assessments.

They have tested a method that could enable risk assessors establish a biological cause-and-effect link between exposure to chemicals such as pesticides and ill health.

Dr Susanne Hougaard Bennekou and Dr Andrea Terron have explained the significance of their work.

What was the aim of your project?

Pesticide risk assessors want to make better use of the information in epidemiological studies. To do this, we need to find a way of confirming or not confirming suggested associations between exposure to chemicals and human diseases.

This task is particularly difficult when the data relate to complex human diseases.

Sometimes there are so many factors involved that it is just not possible to confirm the chemical-disease associations suggested.

We have applied a framework that could establish if there is a plausible link

between a chemical coming into contact with and affecting an organism at cellular level, and a subsequent chain of events leading to the effect (disease).

In other words, to establish whether a specific sequence, or pathway, of events represents a human health hazard, and consequently identify chemicals that need to be considered as potential disease risk factors.

This conceptual framework is known as the adverse outcome pathway (AOP).

How did you apply the AOP?

We designed prototype AOPs for Parkinson’s disease and infant leukaemia, two

diseases for which our 2013 literature review on epidemiological studies showed

consistent associations with pesticide exposure.

And what did you find?

It is clear that the framework is an effective tool for establishing an association between exposure to a chemical and a disease. The overall weight of evidence from the AOPs for both Parkinson’s disease and infant leukaemia showed a strong link between the initial interaction and the adverse outcome.

So have you established a link between exposure to chemicals and these two diseases?

No, we have not established a link between exposure to a chemical and these two diseases. The AOP conceptual framework allows us to assess the plausibility of an association with a single chemical, but this is a long way from showing that a chemical causes a disease or even that it represents a risk factor. That requires a full risk assessment.

For example, a pesticide will not necessarily have an adverse effect when people are exposed to it in real conditions. It has to reach specific cells to have an effect, at a dose high enough to trigger the adverse outcome.

Even then, exposure could be just one risk factor among multiple others for developing Parkinson’s disease and infant leukaemia.

But this is a step forward for the risk assessment of chemicals, including pesticides?

Yes, it is.

The AOP is not intended to be used as a substitute for the data required to assess a pesticide but rather to serve as a complementary tool.

The AOP method could also help to identify data gaps for each step along the pathway and to guide future testing strategies for hazard identification and characterisation.

What is epidemiology?

Epidemiology concerns the analysis of the patterns, causes (for example, smoking, alcohol, virus, exposure to specific chemicals) and effects of health and disease conditions in defined groups of people.

Epidemiology also defines how often diseases occur in different groups of people and why.

The information provided is used to prevent illness, and in the case of exposure to chemicals, to update information on the hazardous properties of a chemical and on the actual risk under past or current exposure conditions.

For a full, in-depth understanding of the issues, consult the scientific opinion adopted by EFSA’s Panel on Plant Protection Products and their Residues.